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Here is a chemical reaction formula: Reactants are:m1_m6_m2:ClC1=CC=C(N)C=C1;m1_m6_m2:N1=CC=CC=C1;m4:C(C)(=O)OCC;m3_m5:C(C=CC1=CC=CC=C1)(=O)Cl, Reagents are:m1_m6_m2:C1(=CC=CC=C1)C;m3_m5:C1(=CC=CC=C1)C;m7:O, and Products are 0:ClC1=CC=C(C=C1)NC(C=CC1=CC=CC=C1)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a mixture of 4-chloroaniline (16.2 g), toluene (120 ml), and pyridine (11 ml) at 0° C., cinnamoyl chloride (20.0 g) in 120 ml of toluene was added dropwise. After stirring 15 minutes at 0° C. the reaction mixture was poured into a mixture of ethyl acetate: water (250 ml:250 ml). The organic layer was separated and extracted with 5% aqueous HCl (3×250 ml), water (1×250 ml), 5% aqueous sodium bicarbonate (3×250 ml), dried over anhydrous sodium sulfate and evaporated yielding the amide as a white solid. |
Here is a chemical reaction formula: Reactants are:m3:BrCC#CCC;m2:N1C(C=CC2=CC=CC=C12)=O;m4:[Cl-].[NH4+];m1_m5:[H-].[Na+], Reagents are:m6_m0:CCCCCC;m1_m5:CN(C)C=O, and Products are 0:ClC1=C2C=CC(N(C2=CC=C1)CC#CCC)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a suspension of NaH (60% in mineral oil, 700 mg) in dry DMF (100 ml) at 0° C. was added the preceding quinolinone (2.05 g) and the mixture was stirred at 0° C. for one half hour. To the resulting suspension was added 1-bromo-2-pentyne (1.6 g) dropwise. The resulting mixture was kept at 0° C. for one half hour and poured into saturated aqueous ammonium chloride (200 ml). The aqueous suspension was extracted with ether (3×100 ml), the combined ether layers washed with brine and dried, yielding the crude product. Trituration with hexane yielded the product as a yellow solid (1 g). |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m6_m5:ClC1=CC=C(C=C1)C(C=O)=CN(C)C;m1_m2_m3_m6_m5:NC(=O)N;m1_m2_m3_m6_m5:Cl;m4:[Cl-].[NH4+], Reagents are:m1_m2_m3_m6_m5:C(C)O;m1_m2_m3_m6_m5:O, and Products are 0:ClC1=CC=C(C=C1)C=1C=NC(NC1)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 2-(4-chlorophenyl)dimethylaminopropenal (Example 145a) (5.13 g), urea (2.4 g), concentrated HCl (10 ml), water (4 ml) and ethanol (150 ml) was refluxed for 4 hours. After cooling to room temperature concentrated ammonium chloride was added until the pH was 7. The resulting yellow solid was filtered off and dried yielding 1.5 g of 5-(4-chlorophenyl)-2-pyrimidinone. |
Here is a chemical reaction formula: Reactants are:m4:[Cl-].[NH4+];m3:BrCC#CCC;m5_m0:CCCCCC;m2:N1C(C=CC=C1)=O;m1_m6:[H-].[Na+], Reagents are:m1_m6:CN(C)C=O, and Products are 0:ClC1=CC=C(C=C1)C=1C=NC(N(C1)CC#CCC)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a suspension of NaH (60% in mineral oil, 340 mg) in dry DMF (75 ml) at 0° C. was added the preceding pyridinone (1.0 g) and the mixture was stirred at 0° C. for one half hour. To the resulting suspension was added 1-bromo-2-pentyne (750 mg) dropwise. The resulting mixture was kept at 0° C. for one half hour and poured into saturated aqueous ammonium chloride (200 ml). The aqueous suspension was extracted with ether (3×100 ml), the combined ether layers washed with brine and dried, yielding the crude product. Trituration with hexane yielded the product as a yellow solid. |
Here is a chemical reaction formula: Reactants are:m1_m3_m2:ClC1=CC=C(C=C1)C=1C=CC(NN1)=O;m1_m3_m2:P12(=S)SP3(=S)SP(=S)(S1)SP(=S)(S2)S3, Reagents are:m1_m3_m2:N1=CC=CC=C1, and Products are 0:ClC1=CC=C(C=C1)C=1C=CC(NN1)=S, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 3.0 g of 6-(4-chlorophenyl)-pyridazinone, 50 ml of dry pyridine and 3.2 g of phosphorus pentasulfide was refluxed for 1 hour, evaporated to dryness and extracted with 200 ml of ether. The ether extract was washed with water (3×100 ml), brine (100 ml), dried over magnesium sulfate and evaporated to yield 3.0 g of 6-(4-chlorophenyl)-pyridazinthione as a yellow solid. |
Here is a chemical reaction formula: Reactants are:m1_m3_m2:ClC1=CC=C(C(=O)NN)C=C1;m1_m3_m2:ClCC(=O)Cl, Reagents are:m1_m3_m2:O1CCOCC1, and Products are 0:ClCC(=O)NNC(C1=CC=C(C=C1)Cl)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of p-chlorobenzoic hydrazide (11.2 g) in dioxane (100 ml) was added chloroacetyl chloride (6 ml). The resulting mixture was refluxed for three hours, cooled to room temperature and filtered. The resulting solid was washed with ethyl ether and dried to yield N'-chloroacetyl-4-chlorobenzoic hydrazide as white solid. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:BrCC(=O)C1=CC=C(C=C1)Cl;m1_m2_m3:COC(=S)NN, Reagents are:m1_m2_m3:C(C)#N, and Products are 0:ClC1=CC=C(C=C1)C1=NNC(SC1)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 2-bromo-p-chloroacetophenone (9.16 g), methoxythiocarbonylhydrazine (13.0 g) and acetonitrile (75 ml) was refluxed overnight and then cooled and filtered. The light yellow solid was washed with hexane and dried yielding 5-(4-chlorophenyl)-3H,6H-1,3,4-thiadiazin-2-one (4.3 g). |
Here is a chemical reaction formula: Reactants are:m1_m3_m2:ClC1=CC=C(C(=O)CCC(=O)O)C=C1;m1_m3_m2:CNN, Reagents are:m1_m3_m2:C(C)O, and Products are 0:ClC1=CC=C(C=C1)C=1CCC(N(N1)C)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a 250 ml flask equipped with magnetic stirrer and reflux condenser was charged 10 g of 3-(4-chlorobenzoyl)-propionic acid, 250 ml of absolute ethanol, and 2.5 ml of methyl hydrazine. The reaction was refluxed for 3 hours and cooled to yield a solid which was collected by vacuum filtration, washed with 50 ml of hexane, and air dried. Isolated 9.5 g of product as a white solid. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4:ClC1=CC=C(C=O)C=C1;m1_m2_m3_m4:C(CCC(=O)C)(=O)O;m1_m2_m3_m4:N1CCCCC1;m1_m2_m3_m4:C1(=CC=CC=C1)C, Reagents are:m5:O, and Products are 0:ClC1=CC=C(C=CC(=O)CCC(=O)O)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a dry 250 ml flask equipped with a magnetic stirrer, Dean-Stark trap, and reflux condenser was charged 15 g of 4-chlorobenzaldehyde, 12.4 g levulenic acid, 5.7 ml of piperidine, and 100 ml of toluene. The reaction was refluxed for 3 hours, after which no water was observed to azeotrope from the solution. The reaction was cooled and stripped to yield a reddish-brown liquid which was triturated with hexane to yield 11.2 g of product as a yellow solid. |
Here is a chemical reaction formula: Reactants are:m1_m3_m2:[N+](=O)([O-])C=1C(=C(C(=O)[O-])C=CC1OC)C;m1_m3_m2:[OH-].[K+], Reagents are:m1_m3_m2:O1CCCC1, and Products are 0:[N+](=O)([O-])C=1C=C(C(=O)O)C=CC1OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a 500 ml erlenmeyer flask with magnetic stirrer was charged 10.3 g of 3-nitro-4-methoxy-methylbenzoate, 400 ml tetrahydrofuran, and 3.2 g of 86% potassium hydroxide. The reaction was stirred for 12 hours at ambient temperature, after which the resulting solid was collected by vacuum filtration and washed with 2×100 ml of ethyl ether. The solid was dissolved in 200 ml of water and acidified to pH 4 with 6N hydrochloric acid. The resulting precipitate was collected by vacuum filtration, washed with 200 ml water, and dried overnight in vacuo at 30° C. Isolated 7.4 g of product as a white solid. |
Here is a chemical reaction formula: Reactants are:m4_m2:C1(=CC=CC2=CC=CC=C12)[Mg]Br;m1:CN(C=1SC2=C(C1C(=O)C1=CC=C(C=C1)OCCN1CCCCC1)C=CC(=C2)OC)C, Reagents are:m3:O1CCCC1;m4_m2:O1CCCC1, and Products are 0:C1(=CC=CC2=CC=CC=C12)C=1SC2=C(C1C(=O)C1=CC=C(C=C1)OCCN1CCCCC1)C=CC(=C2)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of [2-dimethylamino-6-methoxybenzothien-3-yl][4-[2-(1-piperdinyl)ethoxy]phenyl]methanone (1.58 g, 3.6 mmol) (see U.S. Pat. No. 5,420,349) in tetrahydrofuran (THF, 12 mL) was cooled to 0° C. and treated with a 0.65M THF solution of 1-naphthylmagnesium bromide (20.0 mL, 13 mmol) (prepared from 1-bromonaphthalene, catalytic iodine, and magnesium turnings in THF). The mixture was allowed to warm to ambient temperature and when the starting material was consumed, the reaction was quenched with water and extracted with ethyl acetate (a small amount of methanol was added to improve solubility). The organic layer was washed with water (2×), and brine (2×), dried (sodium sulfate), and concentrated. The residue was purified via chromatography (silica gel, 0-10% methanol in methylene chloride) to provide 1.08 g (58%) of the title compound as a yellow foam: 1H NMR (300 MHz, CDCl3) δ1.46 (m, 2H), 1.60 (m, 4H), 2.47 (m, 4H), 2.68 (t, J=5.9 Hz, 2H), 3.92 (s, 3H), 3.96 (t, J=5.9 Hz, 2H), 6.47 (d, J=8.8 Hz, 2H), 7.06 (dd, J=2.3 Hz, 8.9 Hz, 1H), 7.27-7.50 (m, 5H), 7.54 (d, J=8.8 Hz, 2H), 7.67-7.75 (m, 2H), 7.79 (d, J=8.9 Hz, 1H), 8.06-8.09 (m, 1H); MS (FD) m/e 521 (M+). |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4:C1(=CC=CC2=CC=CC=C12)C=1SC2=C(C1C(=O)C1=CC=C(C=C1)OCCN1CCCCC1)C=CC(=C2)OC;m1_m2_m3_m4:C(C)S;m1_m2_m3_m4:[Cl-].[Al+3].[Cl-].[Cl-], Reagents are:m1_m2_m3_m4:C(Cl)Cl, and Products are 0:C1(=CC=CC2=CC=CC=C12)C=1SC2=C(C1C(=O)C1=CC=C(C=C1)OCCN1CCCCC1)C=CC(=C2)O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of the product of Example 1 (1.00 g, 1.92 mmol), ethanethiol (0.45 mL, 6.18 mmol), and aluminum chloride (1.54 g, 11.55 mmol) in anhydrous methylene chloride (40 mL) was stirred for 3.5 hours. The mixture was quenched with saturated potassium sodium tartrate (also known as Rochelle's salt) and extracted with ethyl acetate. The organic layer was washed with saturated sodium potassium tartrate and brine, dried (sodium sulfate), and concentrated. The residue was purified by chromatography (silica gel, 0-10% methanol in methylene chloride) to give 520 mg (53%) of the title product as a dark yellow/green foam: 1H NMR (300 MHz, CDCl3) δ1.46 (m, 2H), 1.65 (m, 4H), 2.54 (m, 4H), 2.73 (t, J=5.4 Hz, 2H), 3.96 (t, J=5.4 Hz, 2H), 6.37 (d, J=8.7 Hz, 2H), 6.88 (dd, J=1.9 Hz, 8.8 Hz, 1H), 7.23-7.29 (m, 2H), 7.37-7.51 (m, 5H), 7.62-7.70 (m, 3H), 8.02-8.05 (m, 1H), 8.28 (br s, 1H); 13C NMR (75 MHz, CDCl3) δ23.3, 24.7, 54.4, 57.0, 64.5, 106.9, 113.0, 115.2, 124.2, 124.3, 125.2, 125.5, 126.1, 127.6, 128.7, 128.7, 130.3, 130.5, 131.2, 131.6, 131.8, 132.8, 133.4, 140.7, 141.1, 154.6, 161.6, 192.1; MS (FD) m/e 508 (MH+); Anal. calc'd. for C32H29NO3S: C, 75.71; H, 5.76; N, 2.76. Found: C, 75.43; H, 6.02; N, 3.03. |
Here is a chemical reaction formula: Reactants are:m6_m2:C1=C(C=CC2=CC=CC=C12)[Mg]Br;m3:CO;m1:CN(C=1SC2=C(C1C(=O)C1=CC=C(C=C1)OCCN1CCCCC1)C=CC(=C2)OC)C, Reagents are:m6_m2:C1CCOC1;m5:C(Cl)Cl;m4:C1CCOC1, and Products are 0:C1=C(C=CC2=CC=CC=C12)C=1SC2=C(C1C(=O)C1=CC=C(C=C1)OCCN1CCCCC1)C=CC(=C2)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: By the method described in Example 1, [2-dimethylamino-6-methoxybenzothien-3-yl][4-[2-(1-piperdinyl)ethoxy]phenyl]methanone (1.58 g, 3.6 mmol) in THF (12 mL) was reacted with a 0.65M THF solution of 2-naphthylmagnesium bromide (15 mL, 9.8 mmol) to provide, after chromatography (silica gel, 5% methanol in methylene chloride) 1.41 g (75%) of the title compound as a green/yellow foam: 1H NMR (300 MHz, CDCl3) δ1.43 (m, 2H), 1.59 (m, 4H), 2.45 (m, 4H), 2.70 (t, J=6.0 Hz, 2H), 3.91 (s, 3H), 4.02 (t, J=6.0 Hz, 2H), 6.72 (d, J=8.7 Hz, 2H), 7.01 (dd, J=2.1 Hz, 8.8 Hz, 1H), 7.38 (d, J=2.3 Hz, 1H), 7.44-7.47 (m, 2H), 7.53 (d, J=8.4 Hz, 1H), 7.60 (d, J=9.3 Hz, 1H), 7.67-7.79 (m, 4H), 7.82 (d, J=8.7 Hz, 2H), 7.94 (d, J=1.6 Hz, 1H); MS (FD) m/e 521 (M+); Anal. calc'd. for C33H31NO3S: C, 75.98; H, 5.99; N, 2.68. Found: C, 76.27; H, 6.10; N, 2.74. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m5:C1=C(C=CC2=CC=CC=C12)C=1SC2=C(C1C(=O)C1=CC=C(C=C1)OCCN1CCCCC1)C=CC(=C2)OC;m1_m2_m3_m5:C(C)S;m1_m2_m3_m5:[Cl-].[Al+3].[Cl-].[Cl-];m4:CO, Reagents are:m1_m2_m3_m5:C(Cl)Cl;m6:C(Cl)Cl, and Products are 0:C1=C(C=CC2=CC=CC=C12)C=1SC2=C(C1C(=O)C1=CC=C(C=C1)OCCN1CCCCC1)C=CC(=C2)O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: By the method described in Example 2, the product of Example 3 (1.35 g, 2.59 mmol), ethanethiol (0.56 mL, 7.69 mmol), and aluminum chloride (2.07 g, 15.52 mmol) were reacted in anhydrous methylene chloride (50 mL) to give, after chromatography (silica gel, 5% methanol in methylene chloride) 1.29 g (98%) of the title product as a yellow foam; 1H NMR (300 MHz, CDCl3) δ1.46 (m, 2H), 1.66 (M, 4H), 2.58 (m, 4H), 2.77 (t, J=5.5 Hz, 2H), 4.04 (t, J=5.5 Hz, 2H), 6.54 (d, J=8.9 Hz, 2H), 6.75 (dd, J=2.2 Hz, 8.8 Hz, 1H), 7.20 (d, J=2.2 Hz, 1H), 7.39-7.46 (m, 4H) 7.64 (d, J=8.6 Hz, 1H), 7.69-7.76 (m, 4H), 7.86 (d, J=1.5 Hz, 1H); 13C NMR (75 MHz, DMSO--d6) δ23.3, 24.9, 53.7, 56.4, 65.3, 106.7, 114.0, 115.0, 123.2, 125.4, 126.3, 126.3, 126.9, 127.0, 127.5, 127.9, 129.1, 130.0, 131.1, 131.2, 131.7, 131.8, 132.1, 138.9, 139.4, 155.4, 162.4, 191.9; MS (FD) m/e 508 (MH+), 507 (M+); Anal. calc'd. for C32H29NO3S: C, 75.71; H, 5.76; N, 2.76. Found: C, 75.86; H, 5.82; N, 2.75. |
Here is a chemical reaction formula: Reactants are:m1:CN(C=1SC2=C(C1C(=O)C1=CC=C(C=C1)OCCN1CCCCC1)C=CC(=C2)OC)C;m4_m2:S1C(=CC=C1)[Mg]Br, Reagents are:m4_m2:C1CCOC1;m3:C1CCOC1, and Products are 0:S1C(=CC=C1)C=1SC2=C(C1C(=O)C1=CC=C(C=C1)OCCN1CCCCC1)C=CC(=C2)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: By the method described in Example 1, [2-dimethylamino-6-methoxybenzothien-3-yl][4-[2-(1-piperdinyl)ethoxy]phenyl]methanone (1.97 g, 4.5 mmol) in THF (15 mL) was reacted with a 0.60M THF solution of 2-thienylmagnesium bromide (31.8 mL, 13.5 mmol) (prepared from 2-bromothiophene, n-butyllithium, and magnesium bromide in ether) at ambient temperature. Purification by chromatography (silica gel, 1:1 hexane:ethyl acetate, 10% methanol, 0.1% ammonium hydroxide) gave 1.55 g (72%) of the title compound as a yellow foam: 1H NMR (300 MHz) δ1.3-1.4 (m, 2H), 1.4-1.6 (m, 4H), 2.42 (m, 4H), 2.66 (t, J=5.8 Hz, 2H), 3.88 (s, 3H), 4.12 (t, J=5.9 Hz, 2H), 6.96 (m, 4H), 7.16 (d, J=2.5 Hz, 1H), 7.35 (d, J=8.9 Hz, 1H), 7.43 (d, J=5.0 Hz, 1H), 7.55 (d, J=2.2 Hz, 1H), 7.77 (d, J=8.8 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ24.1, 25.9, 55.1, 55.6, 57.7, 66.3, 104.4, 114.4, 115.0, 124.2, 127.1, 127.7, 127.7, 130.3, 131.5, 132.3, 133.6, 134.2, 135.0, 140.0, 158.0, 163.4, 192.8; IR (CHCl3) 1649, 1599 cm-1 ; MS (FD+) m/e 477 (M+); Anal. calc'd. for C27H27NO3S2 : C, 67.89; H, 5.70; N, 2.93. Found: C, 68.13; H, 5.89; N, 2.78. |
Here is a chemical reaction formula: Reactants are:m1:CN(C=1SC2=C(C1C(=O)C1=CC=C(C=C1)OCCN1CCCCC1)C=CC(=C2)OC)C;m4_m2:COC1=CC=C(C[Mg]Br)C=C1, Reagents are:m3:C1CCOC1;m4_m2:C1CCOC1, and Products are 0:COC1=CC=C(C=C1)CC=1SC2=C(C1C(=O)C1=CC=C(C=C1)OCCN1CCCCC1)C=CC(=C2)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: By the method described in Example 1, [2-dimethylamino-6-methoxybenzothien-3-yl][4-[2-(1-piperdinyl)ethoxy]phenyl]-methanone (6.0 g, 13.7 mmol) in THF (51 mL) was reacted with a 0.83M THF solution of 4-methoxybenzylmagnesium bromide (19.8 mL, 16.4 mmol) (prepared from 4-methoxybenzylchloride and magnesium turnings in THF) at ambient temperature. Purification by chromatography (silica gel, 1:1 hexane:ethyl acetate, 0.1% ammonium hydroxide) and recrystallization from ethyl acetate gave 2.08 g (29%) of the title compound as tan crystals, mp 126° C.: 1H NMR (300 MHz) δ1.3-1.5 (m, 2H), 1.5-1.7 (m, 4H), 2.4-2.6 (br m, 4H), 2.77 (br m, 2H), 3.73 (s, 3H), 3.83 (s, 3H), 4.08 (s, 2H), 4.23 (br m, 2H), 6.82 (d, J=8.5 Hz, 2H), 6.90 (dd, J=2.5, 8.8 Hz, 1H), 7.06 (d, J=8.7 Hz, 2H), 7.16 (d, J=8.6 Hz, 2H), 7.27 (d, J=8.9 Hz, 1H), 7.43 (d, J=2.3 Hz, 1H), 7.80 (d, J=8.7 Hz, 2H); IR (CHCl3) 1645, 1600 cm-1 ; HRMS (FAB+) m/e calc'd for C31H34NO4S 516.2208 (MH+), found 516.2200; Anal. calc'd. for C31H33 NO4S.0.5H2O: C, 70.95; H, 6.54; N, 2.67. Found: C, 71.17; H, 6.51; N, 2.56. |
Here is a chemical reaction formula: Reactants are:m4:C(C)N(CC)CC;m3_m7:C(C)OC1=CC=C(N)C=C1;m1_m5:CCC(=S)OCC;m2_m6:ClCl, Reagents are:m3_m7:C(Cl)Cl;m1_m5:C(Cl)Cl;m2_m6:C(Cl)Cl;m8:O, and Products are 0:C(C)OC=1C=C2CC(NC2=CC1)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 23.6 g of ethyl methylthioacetate in 60 ml of DCM are added to a solution, cooled to about -70° C., of 12.5 g of chlorine in 400 ml of DCM. After stirring for 5 minutes at the same temperature, a solution of 4-ethoxyaniline (48.3 g) in 120 ml of DCM is added. The mixture is stirred for one hour at about -70° C., 39.3 ml of triethylamine are added and the resulting mixture is allowed to warm up to room temperature. 200 ml of water are added and the organic phase is decanted, dried over magnesium sulfate and evaporated under reduced pressure. The residue is taken up with 500 ml of isopropanol and 20 ml of concentrated hydrochloric acid. The mixture is stirred for about 16 hours at room temperature and filtered and the precipitate is separated off. The filtrate is concentrated under reduced pressure to give the expected product. |
Here is a chemical reaction formula: Reactants are:m1_m2:FC1=CC=C(C(=O)Cl)C=C1;m1_m2:C(C)O, Reagents are:, and Products are 0:FC1=CC=C(C(=O)OCC)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture containing 35 g of 4-fluorobenzoyl chloride in 50 ml of 100% ethanol is refluxed for 15 minutes. 35 g of the ethyl 4-fluorobenzoate obtained are mixed with 22 g of imidazole and 61 g of potassium carbonate in 35 ml of DMSO. The mixture is heated for 18 hours at 120°-130° C. and 500 ml of iced water are then added. A precipitate forms and the expected product crystallizes from iso ether. |
Here is a chemical reaction formula: Reactants are:m1_m3_m2_m4:BrCC(=O)C1=CC=C(OCC(=O)OC)C=C1;m1_m3_m2_m4:N1=CC=C(C=C1)N1CCNCC1, Reagents are:m1_m3_m2_m4:C(C)#N;m1_m3_m2_m4:C(C)#N, and Products are 0:N1=CC=C(C=C1)N1CCN(CC1)CC(=O)C1=CC=C(OCC(=O)OC)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of methyl 4-bromoacetylphenoxyacetate (4.3 g) in acetonitrile (50 ml) was added dropwise over 40 minutes to a stirred solution of 1-(4-pyridyl)piperazine (4.9 g) in acetonitrile (100 ml). Stirring was continued for a further 1.5 hours, then the solution was filtered and the filtrate evaporated in vacuo. The solid residue was triturated with water (50 ml), then dried and suspended in methylene chloride (50 ml). The suspension was then filtered and the filtrate concentrated to a small volume. Purification by flash chromatography on neutral alumina eluting first with dichloromethane, then 0.5% v/v methanol/dichloromethane and finally 1% v/v methanol/dichloromethane gave the title compound, 1.93 g, as a solid: m.p. 150°-152° C.; NMR(d6DMSO) δ 8.14(2H,d), 7.98(2H,d), 7.03(2H,d), 6.78(2H,d), 4.90(2H,s), 3.83(2H,s), 3.72(3H,s), 3.34(4H,bt), 2.65(4H,bt); m/e 370 (M+H)+ ; calculated for C20H23N3O4 : C, 65.0; H, 6.3; N, 11.4 found: C 65.2; H, 6.4; N, |
Here is a chemical reaction formula: Reactants are:m1_m3_m2:N1=CC=C(C=C1)N1CCN(CC1)CC(=O)C1=CC=C(OCC(=O)OC)C=C1;m1_m3_m2:[OH-].[Na+], Reagents are:m4:O;m1_m3_m2:CO, and Products are 0:N1=CC=C(C=C1)N1CCN(CC1)CC(=O)C1=CC=C(OCC(=O)O)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred solution of the product of Example 1 (550 mg) in methanol (10 ml) was treated with a M sodium hydroxide solution (1.65 ml) and stirring continued for a further 2 hours. The mixture was diluted with water (10 ml) and the resulting solution concentrated in vacuo. Water (20 ml) was added and then a M hydrochloric acid solution (1.65 ml). On cooling to 4° C., a solid precipitated. This mixture was concentrated in vacuo, the solid collected and washed with ice-water, then dried to give the title compound, 320 mg, as a solid: m.p. 294°-296° C; NMR (d6DMSO+TFA) δ 8.34(2H,d), 7.95(2H,d), 7.26(2H,d), 7.10(2H,d), 5.06(2H,s), 4.82(2H,s), 4.06(4H,bs), 3.52(4H,bs); m/e 356(M+H)+ ; calculated for C19H21N3O4 : C, 64.2; H, 6.0; N, 11.8. found: C, 64.1; H, 6.1; N, 11.6%. |
Here is a chemical reaction formula: Reactants are:m1:N1=CC=C(C=C1)N1CCN(CC1)CC(=O)C1=CC(=C(OCC(=O)OC)C=C1)OC, Reagents are:m2:O, and Products are 0:N1=CC=C(C=C1)N1CCN(CC1)CC(=O)C1=CC(=C(OCC(=O)O)C=C1)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: In a similar manner to Example 2, but starting from the product of Example 5, the title compound was prepared in 47% yield: m.p. 218°-224° C.; NMR(d6DMSO) δ 8.16(2H,d), 7.65(1H,dd), 7.53(1H,d), 6.92(1H,d), 6.85(2H,d), 4.73(2H,s), 3.86(2H,s), 3.82(3H,s), 3.36(4H,t), 2.63(4H,t); m/e 386(M+H)+ ; calculated for C20H23N3O5. H2O: C, 59.5; H, 6.2; N, 10.4. found: C, 59.5; H, 5.9; N, 10.1%. |
Here is a chemical reaction formula: Reactants are:m1_m3_m2_m4:ClCC(=O)C1=CC=C(C=C1)CC(=O)OC;m1_m3_m2_m4:N1=CC=C(C=C1)N1CCNCC1, Reagents are:m1_m3_m2_m4:C(C)#N;m1_m3_m2_m4:C(C)#N, and Products are 0:N1=CC=C(C=C1)N1CCN(CC1)CC(=O)C1=CC=C(C=C1)CC(=O)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of methyl 4-chloroacetylphenylacetate (260 mg) in acetonitrile (4 ml) was added dropwise over 15 minutes to a stirred solution of 1-(4-pyridyl)piperazine (375 mg) in acetonitrile (10 ml) and the mixture stirred overnight. The supernatent was decanted from the solid formed, concentrated in vacuo and purified by flash chromatography on neutral alumina, eluting with dichloromethane then 0.25% v/v methanol/dichloromethane and finally 0.5% v/v methanol dichloromethane. Concentration of the fractions in vacuo gave the title compound, 96 mg, as a white crystalline solid: m.p. 127°-129° C.; NMR (d6 DMSO) δ 8.15(2H,d), 7.98(2H,d), 7.41(2H,d), 6.81(2H,d), 3.91(2H,s), 3.78(2H,s), 3.53(3H,s), 3.33(4H,t), 2.64(4H,t); m/e 354(M+H )+ ; calculated for C20H23N3O3 : C, 68.0; H, 6.6; N, 11.9. found: C, 68.2; H, 6.6; N, 11.9%. |
Here is a chemical reaction formula: Reactants are:m1_m3_m2_m4:CCC(=O)C1=CC=C(OCC(=O)OC)C=C1;m1_m3_m2_m4:N1=CC=C(C=C1)N1CCNCC1, Reagents are:m1_m3_m2_m4:C(C)#N;m1_m3_m2_m4:C(C)#N, and Products are 0:N1=CC=C(C=C1)N1CCN(CC1)C(C(=O)C1=CC=C(OCC(=O)OC)C=C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of RS methyl 4-(2-methylacetyl)phenoxyacetate (1.2 g) in acetonitrile (10 ml) was added dropwise over 30 minutes to a stirred solution of 1-(4-pyridyl)piperazine (1.3 g) in acetonitrile (30 ml) and the mixture stirred overnight. The mixture was then filtered and the filtrate evaporated to give an oil. Purification by flash chromatography, eluting first with dichloromethane then successively 2.5%, 3%, 4%, 5% and 10% v/v methanol/dichloromethane gave the title compound, 220 mg as a solid: m.p. 81°-83° C.; NMR (d6DMSO) δ 8.13(2H,d), 8.06(2H,d), 7.02(2H,d), 6.77(2H,d), 4.92(2H,s), 4.33(1H,q), 3.72(3H,s), 3.26(4H,t), 2.63(4H,t), 1.16(3H,d); m/e 384(M+H)+ ; calculated for C21H25N3O4 : C, 65.8; H, 6.6; N, 11.0. found C, 65.7; H, 6.8; N, 10.9%. |
Here is a chemical reaction formula: Reactants are:m1_m4:N1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(C=C1)O;m2:[H-].[Na+];m3:BrCCCC(=O)OCC, Reagents are:m1_m4:CN(C)C=O, and Products are 0:N1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(OCCCC(=O)OCC)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred suspension of 4-(4-(4-pyridyl)piperazin-1-yl)-phenol (1.34 g) in dry DMF (20 ml) was treated with sodium hydride (60% dispersion in mineral oil, 0.21 g) and the mixture stirred for 1 hour. To the resulting solution was added ethyl 4-bromobutyrate and the mixture was stirred for 16 hours. Solvent was evaporated under reduced pressure and the residue was partitioned between ethyl acetate and water. The organic layer was washed with water, filtered through phase separating paper (Whatman 1PS) and evaporated. The residue was purified by flash chromatography on silica, eluting with 1-5/92.5/6 v/v/v methanol/ethyl acetate/aqueous ammonia (SG 0.89) and recrystallised from ethyl acetate/hexane to give the title compound (0.7 g) as a solid: m.p. 84°-85° C.; NMR (CDCl3) δ 8.3(2H,d); 6.86(4H,c); 6.72(2H,d); 4.12(2H,q); 4.0(2H,t); 3.47(4H,m); 3.20(4H,m); 2.5(2H,t); 2.1(2H,m); 1.26(3H,t); m/e 370(M+H)+ ; calculated for C21H27N3O3C, 68.3; H, 7.4; N, 11.4. Found: C, 68.1; H, 7.4; N, 11.1%. |
Here is a chemical reaction formula: Reactants are:m3:N;m1_m2:N1(CCNCC1)C1=CC=C(C=C1)OC;m1_m2:Cl.ClC1=CC=NC=C1, Reagents are:m4:O, and Products are 0:N1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(C=C1)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 4-(piperazin-1-yl)anisole (4.24 g) and 4-chloropyridine hydrochloride (3.35 g) were intimately mixed and heated at 160°-170° C. (bath temperature) for 7 minutes. The solid obtained on cooling was dissolved in water (75 ml) and the solution basified with aqueous ammonia. The solid precipitate was extracted into ethyl acetate and the organic extract washed with water, filtered through phase separating paper (Whatman 1PS) and evaporated. The residue was recrystallised from ethanol to give 4-[4-(4-pyridyl)-piperazin-1-yl]anisole (1.84 g) as a solid: m.p. 165°-167° C.; NMR (CDCl3) δ8.3(2H,d); 6.86(4H,m); 6.71(2H,d); 3.78(3H,s); 3.46(4H,m); 3.2(4H,m). |
Here is a chemical reaction formula: Reactants are:m2:O;m1_m4:N1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(C=C1)OC;m3:N, Reagents are:m1_m4:Br, and Products are 0:N1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(C=C1)O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: The product from step (i) (1.5 g) in concentrated hydrobromic acid (30 ml) was heated under argon at 130°-135° C. for 21/2 hours. The solution was cooled, poured into water (150 ml) and basified with aqueous ammonia. The precipitate was filtered, washed with water and dried to give 4-[4-(4-pyridyl)piperazin-1-yl]phenol (1.36 g) as a solid: m.p. 310°-312° C.; NMR(d6DMSO) δ 8.2(2H,d); 6.8(4H,m); 6.66(2H,d); 3.45(4H,m); 3.08(4H,m). |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:N1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(C=C1)O;m1_m2_m3:[OH-].[Na+], Reagents are:m1_m2_m3:C(C)O, and Products are 0:N1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(OCCCC(=O)O)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of the product of Example 25 (0.1 g) in aqueous sodium hydroxide (1N, 0.8 ml) and ethanol (2 ml) was kept for 2 hours. The solution was evaporated and the residue dissolved in water (5 ml). Hydrochloric acid (1N, 0.8 ml) was added and the precipitate was filtered and washed with water and ether to give the title compound as a solid: m.p 305°-306° C.; m/e 342(M+H)+ ; NMR(d6DMSO) δ 8.0(2H,d); 6.72(6H,m); 3.74(2H,t); 3.3(4H,m); 2.94(4H,m); 2.19(2H,t); 1.72(2H, m); calculated for C19H23N3O3 : C, 66.8; H, 6.8; N, 12.3. Found: C, 67.0; H, 6.8; N, 12.2%. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C(C(=O)Cl)(=O)Cl;m1_m2_m3:N1=CC=C(C=C1)C1N(CCNC1)C1=CC=C(C(=O)O)C=C1, Reagents are:m1_m2_m3:ClCCl;m4:CN(C)C=O, and Products are 0:N1=CC=C(C=C1)C1N(CCNC1)C1=CC=C(C(=O)Cl)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Oxalyl chloride (0.5 ml) was added to a stirred suspension of 4-((4-pyridyl)piperazin-1-yl)benzoic acid in dichloromethane (15 ml), followed by DMF (1 drop). The mixture was stirred for 2 hours and evaporated to dryness to give 4-[(4-pyridyl)piperazin-1-yl]benzoyl chloride which was used immediately. |
Here is a chemical reaction formula: Reactants are:m1_m2:[H-].[Na+];m1_m2:CCCCCC;m3_m6:CC(=O)C1=CC(=C(C(=C1)Cl)O)Cl;m4:BrCC(=O)OC, Reagents are:m3_m6:CN(C)C=O;m7:O;m5:CN(C)C=O, and Products are 0:C(C)(=O)C1=CC(=C(OCC(=O)OC)C(=C1)Cl)Cl, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Sodium hydride (50% w/w dispersion in mineral oil, 1.32 g) was treated under argon with repeated washes of hexane. The oil-free residue was suspended in dry DMF (10 ml) and, with stirring and cooling (ice-bath), a solution of 3,5-dichloro-4-hydroxyacetophenone (5.13 g) in dry DMF (15 ml) was added dropwise. Stirring was continued for 30 minutes when methyl bromoacetate (3.06 ml) was added dropwise and stirring was continued for a further 18 hours at ambient temperature. The reaction mixture was added to water, the mixture was extracted twice with ethyl acetate, the organic phases dried (MgSO4), filtered and then evaporated. The residue, after recrystallisation from hexane (250 ml), gave methyl 4-acetyl-2,6-dichlorophenoxyacetate, 4.25 g, as white crystals: NMR (d6DMSO) δ 8.00 (2H, s), 4.80 (2H, s), 3.73 (3H, s), 2.59 (3H, s). |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4:CC1=C(C=CC(=C1)O)C(=O)C;m1_m2_m3_m4:C([O-])([O-])=O.[K+].[K+];m1_m2_m3_m4:BrCC(=O)OC, Reagents are:m1_m2_m3_m4:CC(=O)C, and Products are 0:C(C)(=O)C1=C(C=C(OCC(=O)OC)C=C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 4-hydroxy-2-methylacetophenone (4.8 g), anhydrous potassium carbonate (5.3 g) and methyl bromoacetate (3.55 ml) in anhydrous acetone (100 ml) was stirred for 2 days. The mixture, after filtration and evaporation of the solvent, gave methyl 4-acetyl-3-methylphenoxyacetate, 6.6 g, as a crystalline solid: m.p. 49°-50° C.; NMR (d6DMSO) δ 7.84 (1H, d), 6.83 (2H, m), 4.87 (2H, s), 3.71 (3H, s), 2.50 (3H, s), 2.45 (3H, s). |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4:CC1=C(C=CC(=C1)C(=O)C)O;m1_m2_m3_m4:BrCC(=O)OC;m1_m2_m3_m4:C([O-])([O-])=O.[K+].[K+], Reagents are:m1_m2_m3_m4:CC(=O)C, and Products are 0:C(C)(=O)C1=CC(=C(OCC(=O)OC)C=C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 4-hydroxy-3-methylacetophenone (5 g), methyl bromoacetate (3.70 ml) and anhydrous potassium carbonate (5.52 g) in acetone (100 ml) was stirred for 66 hours. The mixture was filtered and the filtrate evaporated to give an oil which crystallised on standing giving methyl 4-acetyl-2-methylphenoxyacetate, 7.2 g: m.p. 51°-53° C.; NMR (d6DMSO) δ 7.79 (1H, s), 7.77 (1H, d), 6.94(1H,d), 4.93 (2H, s), 3.71 (3H, s), 2.50 (3H, s+DMSO), 2.24 (3H, s). |
Here is a chemical reaction formula: Reactants are:m2:[OH-].[Na+];m1_m3:N1=CC=C(C=C1)N1CCN(CC1)CC(=O)C1=CC=C(C(=O)OCC)C=C1, Reagents are:m1_m3:CO, and Products are 0:N1=CC=C(C=C1)N1CCN(CC1)CC(=O)C1=CC=C(C(=O)[O-])C=C1.[Na+], please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred suspension of the product of Example 77 (353 mg) in methanol (5 ml) was treated with a 1 molar sodium hydroxide solution (3 ml). After 2 hours, the cream coloured solid was collected, washed with a little methanol and dried to give the title compound, 240 mg, m.p.>300° C.; NMR (d6DMSO) δ 8.15 (2H, d), 8.05 (4H, t, AB pattern), 6.85 (2H, d), 3.97 (2H, s), 3.38 (4H, t), 2.65 (4H, t), m/e 348 (M+H)+ ; calculated for C18H18N3NaO3. 0.25H2O: C, 61.4; H, 5.3; N, 11.9. found: C, 61.3; H, 5.2; N, 11.7%. |
Here is a chemical reaction formula: Reactants are:m3:O1CCOCC1;m2:Br;m1:N1=CC=C(C=C1)N1CCN(CC1)CC(=O)C1=CC=C(OC(C(=O)OC)(C)C)C=C1, Reagents are:m4:O;m5:O, and Products are 0:Br.Br.N1=CC=C(C=C1)C1N(CCNC1)CC(=O)C1=CC=C(OC(C(=O)O)(C)C)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of methyl 2-[4-[2-[4-(4-pyridyl)piperazin-1-yl]-acetyl]phenoxy]isobutyrate (50 mg), 48% w/v hydrobromic acid (0.74 ml), dioxane (1 ml) and water (3 ml) was heated at 95° C. for 4 hours. The solution was cooled, diluted with water and freeze-dried to give the title compound, 40 mg, as a pale yellow solid: m.p. 163°-167° C.; NMR (D2O) δ 8.40 (2H, d), 8.16 (2H, d), 7.40 (2H, d), 7.21 (2H, d), 5.21 (2H, s), 4.32 (4H, b), 3.89 (4H, bt), 1.86 (6H, s); m/e 384 (M+H)+ ; calculated for C21H25N3.2HBr.2H2O: C, 43.3; H, 5.3; N, 7.2. found: C, 43.6; H, 5.3; N, 7.3%. |
Here is a chemical reaction formula: Reactants are:m4_m0:C(C)OCC;m1_m5_m2_m3_m6:BrCC(=O)C1=CC=C(OC(C(=O)OC)(C)C)C=C1;m1_m5_m2_m3_m6:N1=CC=C(C=C1)N1CCNCC1;m1_m5_m2_m3_m6:C(C)N(CC)CC, Reagents are:m1_m5_m2_m3_m6:C(C)#N;m1_m5_m2_m3_m6:C(C)#N, and Products are 0:N1=CC=C(C=C1)N1CCN(CC1)CC(=O)C1=CC=C(OC(C(=O)OC)(C)C)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: The product from step (i) above (2.00 g) in acetonitrile (10 ml) was added dropwise over 15 minutes to a stirred solution of 1-(4-pyridyl)piperazine (1.04 g) and triethylamine (0.89 ml) in acetonitrile (15 ml) and the mixture stirred overnight. The precipitated solid was removed by filtration and the filtrate evaporated. Purification of the residue by flash chromatography on silica, eluting with 0 to 5% v/v methanol/dichloromethane, gave a yellow gum. Trituration of this gum with diethyl ether gave methyl 2-[4-[2-[4-(4-pyridyl)piperazin-1-yl]acetyl]phenoxy]isobutyrate, 170 mg, as a white solid: m.p. 88°-90° C.; NMR (d6DMSO) δ 8.15 (2H, d), 7.96 (2H, d), 6.82 (4H, m), 3.92 (2H, s), 3.70 (3H, s), 3.33 (4H, t), 2.63 (4H, t), 1.60 (6H, s); m/e 398 (M+H)+ ; calculated for C22H27N3O4.0.25H2O: C, 65.8; H, 6.8; N, 10.5. found: C, 65.8; H, 7.1; N, 10.4%. |
Here is a chemical reaction formula: Reactants are:m1:BrCC(=O)C1=CC=C(OCC(=O)OCC)C=C1;m2_m3:N1=CC=C(C=C1)N1CCNCC1, Reagents are:m2_m3:C(C)#N, and Products are 0:N1=CC=C(C=C1)N1CCN(CC1)CC(=O)C1=CC=C(OCC(=O)OCC)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Ethyl 4-bromoacetylphenoxyacetate (6.0 g) was added to a stirred, cooled (4° C.) solution of 1-(4-pyridyl)piperazine (6.5 g) in acetonitrile (225 ml). Stirring was continued for 1 hour at 4° C., then overnight at ambient temperature when the precipitated solid was removed by filtration. The filtrate was evaporated in vacuo and the solid residue triturated with water, filtered, then washed with water and dried. Recrystallisation from a small volume of ethanol gave the title compound, 1.71 g, as a cream coloured solid: m.p. 113°-114° C.; NMR (d6DMSO) δ 8.15 (2H, d), 7.98 (2H, d), 7.02 (2H, d), 6.80 (2H, d), 4.89 (2H, d), 4.17 (2H, q), 3.84 (2H, s), 3.32 (4H, t), 2.62 (4H, t), 1.22 (3H, t); m/e 384 (M+H)+ ; calculated for C21H25 N3O4 : C, 65.8; H, 6.6; N, 11.0. found: C, 65.5; H, 6.6; N, 10.8%. |
Here is a chemical reaction formula: Reactants are:m2_m3:N1=CC=C(C=C1)N1CCNCC1;m1:BrCC(=O)C1=CC=C(OCC(=O)OC(C)C)C=C1, Reagents are:m2_m3:C(C)#N, and Products are 0:N1=CC=C(C=C1)N1CCN(CC1)CC(=O)C1=CC=C(OCC(=O)OC(C)C)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: iso-Propyl 4-bromoacetylphenoxyacetate (6.3 g) was added to a stirred, cooled (4° C.) solution of 1-(4-pyridyl)piperazine (6.5 g) in acetonitrile (225 ml). Stirring was continued for 1 hour at 4° C., then overnight at ambient temperature when the precipitated solid was removed. The filtrate was evaporated in vacuo and the residue partitioned between ethyl acetate and water. The organic phase was dried (MgSO4) and evaporated. Purification by flash chromatography on silica, eluting firstly with 0 to 10% v/v methanol/dichloromethane and then toluene/ethyl acetate/.880 ammonium hydroxide/ethanol (60:20:10:35 v/v/v/v), gave a cream solid. Recrystallisation from iso-propanol gave the title compound, 2.1 g: m.p. 121°-122° C.; NMR (d6DMSO) δ 8.14 (2H, d), 7.98 (2H, d), 7.02 (2H, d), 6.80 (2H, d), 4.99 (1H, m), 4.85 (2H, s), 3.84 (2H, s), 3.33 (4H, t), 2.62 (4H, t), 1.22 (6H, d); m/e 398 (M+H)+ ; calculated for C22H27N3O4 : C, 66.5; H, 6.9; N, 10.6. found: C, 65.8; H, 6.8; N, 10.4%. |
Here is a chemical reaction formula: Reactants are:m1_m3:N1=CC=C(C=C1)N1CCN(CC1)CC(=O)C1=CC=C(OCC(=O)OC)C=C1;m2:N, Reagents are:m1_m3:CO, and Products are 0:N1=CC=C(C=C1)N1CCN(CC1)CC(=O)C1=CC=C(OCC(=O)N)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of the product of Example 1 (200 mg) in methanol (10 ml), prepared under argon, was cooled to 4° C. and saturated with dry ammonia gas, then sealed in a pressure bottle and kept for 2 days. The orange crystals which formed, after filtration and washing with a little methanol, gave the title compound, 140 mg: m.p. 247° to 248° C.; NMR (d6DMSO) δ 8.16 (2H, d), 7.99 (2H, d), 7.55 (1H, bs), 7.37 (1H, bs), 7.02 (2H, d), 6.81 (2H, d), 4.54 (2H, s), 3.85 (2H, s), 3.33 (4H, t), 2.60 (4H, t); m/e 355 (M+H)+ ; calculated for C19 H22N4O3 : C, 64.4; H, 6.3; N, 15.8. found: C, 64.4; H, 6.4; N, 15.6%. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:N1=CC=C(C=C1)N1CCN(CC1)CC(=O)C1=CC=C(OCC(=O)OC)C=C1;m1_m2_m3:CN, Reagents are:m1_m2_m3:C(C)O, and Products are 0:N1=CC=C(C=C1)N1CCN(CC1)CC(=O)C1=CC=C(OCC(=O)NC)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A suspension of the product of Example 1 (100 mg) in a 33% w/v solution of methylamine in ethanol (3 ml) was stirred for 18 hours. The solid formed, after filtration and washing with a little ethyl acetate, gave the title compound, 65 mg: m.p. 169°-171° C.; NMR (d6DMSO) δ 8.14 (2H, d), 8.06 (1H, bq), 8.00 (2H, d), 7.05 (2H, d), 6.80 (2H, d), 4.56 (2H, s), 3.82 (2H, s), 3.30 (4H, t), 2.66 (3H, d), 2.61 (4H, t); m/e 369 (M+H)+ ; calculated for C20H24N4O3 : C, 65.2; H, 6.6; N, 15.2. found: C, 65.0; H, 6.8; N, 15.1%. |
Here is a chemical reaction formula: Reactants are:m1_m2:N1=CC=C(C=C1)N1CCN(CC1)CC(=O)C1=CC=C(OCC(=O)OC)C=C1;m1_m2:COCCN, Reagents are:, and Products are 0:N1=CC=C(C=C1)N1CCN(CC1)CC(=O)C1=CC=C(OCC(=O)NCCOC)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A suspension of the product of Example 1, (100 mg) in 2-methoxyethylamine (1 ml) was stirred for 18 hours. Filtration of the solid and washing with ethyl acetate gave the title compound, 70 mg, as a white crystalline solid: m.p. 142°-145° C.; NMR (d6DMSO+d4 acetic acid) δ 8.20 (2H, d), 8.00 (2H, d), 7.14 (2H, d), 7.06 (2H, d), 4.62 (2H, s), 3.72 (4H, t), 3.38 (4H, m), 3.26 (3H, s), 2.78 (4H, t); m/e 413 (M+H)+ ; calculated for C22H28N4O4 : C, 64.1; H, 6.8; N, 13.6. found: C, 63.9; H, 6.8; N, 13.3%. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C(C)(=O)C1=CC=C(OCC(=O)NCC(=O)OC)C=C1;m1_m2_m3:BrN1C(CCC1=O)=O, Reagents are:m1_m2_m3:C(Cl)(Cl)(Cl)Cl, and Products are 0:BrCC(=O)C1=CC=C(OCC(=O)NCC(=O)OC)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: The product of step (i) (3.00 g) and N-bromosuccinimide (2.02 g) in carbon tetrachloride (50 ml) was heated at reflux temperature for 64 hours. The solvent was evaporated and the black residue dissolved in methanol/ethyl acetate, treated with charcoal, filtered and then evaporated. The resulting brown oil was purified by flash chromatography on silica, eluting with dichloromethane. Trituration with hexane gave methyl N-[4-(bromoacetyl)phenoxyacetyl]glycinate, 0.85 g, as a solid: mp softens 109°-111° C.; NMR (d6DMSO) δ 8.60 (1H, bt), 7.99 (2H, d), 7.09 (2H, d), 4.84 (2H, s), 4.69 (2H, s), 3.91 (2H, d), 3.64 (3H, s). |
Here is a chemical reaction formula: Reactants are:m1_m2:[H-].[Na+];m1_m2:CCCCCC;m3:OC1=CC=C(C=C1)CC(=O)O;m4:C(C1=CC=CC=C1)Br, Reagents are:m5:CN(C)C=O, and Products are 0:OC1=CC=C(C=C1)CC(=O)OCC1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Sodium hydride (50% w/w dispersion in mineral oil, 3.7 g) was treated under argon with repeated washes of hexane. The oil-free residue was suspended in dry DMF (100 ml) and 4-hydroxyphenylacetic acid (13.0 g) was added portionwise to the stirred cooled (4° C.) mixture. After 30 minutes, benzyl bromide (9.2 ml) was added dropwise and, after a further 1 hour at 4° C., stirring was continued overnight at ambient temperature. The solvent was evaporated in vacuo and the residue partitioned between ethyl acetate and water. The aqueous phase was re-extracted with further ethyl acetate and the combined organic extracts washed with water and brine, then dried (MgSO4) and evaporated. The crystalline residue gave benzyl 4-hydroxyphenylacetate, 17.8 g, as off-white crystals: m.p. 70°-72° C.; NMR (CDCl3) δ 7.32(5H, m), 7.14(2H, d), 6.76(2H, d), 5.12(2H, s), 3.59(2H, s); m/e 242 (M.)+. |
Here is a chemical reaction formula: Reactants are:m3:OC1=CC=C(C=C1)CC(=O)OCC1=CC=CC=C1;m4:BrCC(=O)OC(C)(C)C;m1_m2:[H-].[Na+];m1_m2:CCCCCC, Reagents are:m5:CN(C)C=O, and Products are 0:C(C1=CC=CC=C1)OC(=O)CC1=CC=C(OCC(=O)OC(C)(C)C)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Sodium hydride (50% w/w dispersion in mineral oil, 2.1 g) was treated under argon with repeated washes of hexane. The oil-free residue was suspended in dry DMF (130 ml) and the product from step (i) (10 g) added in three portions to the cooled (4° C.) stirred mixture. Stirring was continued for a further 15 minutes when tertiary butyl bromoacetate (7.0 ml) was added dropwise over 15 minutes. After 1 hour at 4° C., the mixture was stirred for 6 hours at ambient temperature. The solvent was evaporated in vacuo and the residue partitioned between ethyl acetate and water. The aqueous phase was re-extracted with further ethyl acetate and the combined organic phases washed with water and brine, then dried (MgSO4) and evaporated. The residue, after purification by flash chromatography on silica eluting with dichloromethane, gave tertiary butyl 4-(benzyloxycarbonylmethyl)phenoxyacetate, 7.5 g, as a colourless oil: NMR (CDCl3) d 7.31(5H, m), 7.20(2H, m), 6.85(2H, m), 5.12(2H, s), 4.49(2H, s), 3.60(2H, s), 1.48(9H, s); m/e 356 (M.)+. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4_m5:CCOC(=O)/N=N/C(=O)OCC;m1_m2_m3_m4_m5:N1=CC=C(C=C1)N1CCC(CC1)O;m1_m2_m3_m4_m5:OC1=CC=C(OCC(=O)OC)C=C1;m1_m2_m3_m4_m5:C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1, Reagents are:m1_m2_m3_m4_m5:C1CCOC1, and Products are 0:N1=CC=C(C=C1)N1CCC(CC1)OC1=CC=C(OCC(=O)OC)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Diethylazodicarboxylate (0.47 ml) was added dropwise over 30 minutes to a stirred mixture of 1-(4-pyridyl)-4-piperidinol (534 mg), methyl 4-hydroxyphenoxyacetate (546 mg), triphenylphosphine (787 mg) and dry THF (30 ml) in an atmosphere of argon and cooled to 4° C. After 1 hour at 4° C., the mixture was allowed to reach ambient temperature and stirred for 48 hours. The solvent was removed by evaporation and the residue purified by flash chromatography on silica eluting with 5% v/v methanol/dichloromethane. Recrystallisation from ethyl acetate/hexane gave the title compound, 532 mg, as a white solid: m.p. 74°-76° C.; NMR (d6DMSO) δ 8.15(2H, bd), 6.89(6H, m), 4.71(2H, s), 4.50(1H, m), 3.70(2H, m), 3.69(3H, s), 3.23(2H, m), 1.96(2H, m), 1.62(2H, m); m/e 343 (M+H)+ ; calculated for C19H22N2O4 : C, 66.7; H, 6.5; N, 8.2. found: C, 66.2; H, 6.7; N, 8.2%. |
Here is a chemical reaction formula: Reactants are:m2:OC1=CC=C(C=C1)CCC(=O)OC;m1:OCC1CCN(CC1)C1=CC=NC=C1, Reagents are:, and Products are 0:N1=CC=C(C=C1)N1CCC(CC1)COC1=CC=C(C=C1)CCC(=O)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Following the method of Example 96, but starting from 4-(4-hydroxymethylpiperidin-1-yl)pyridine and methyl 3-(4-hydroxyphenyl)propionate, the title compound was prepared in 14% yield: m.p. 96.5°-98.5° C.; NMR (d6DMSO) δ 8.13(2H, d), 7.11(2H, d), 6.83(4H, m), 3.97(2H, dm), 3.81(2H, d), 3.56(3H, s), 2.87(2H, dr), 2.77(2H, t), 2.57(2H, t), 2.01(1H, m), 1.84(2H, m), 1.30(2H, m); m/e 355 (M+H)+ ; calculated for C21H26 N2O3.0.75H2O: C, 68.5; H, 7.2; N, 7.8. found: C, 68.5; H, 7.5; N, 7.6%. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m5:C(C)(=O)Cl;m1_m2_m3_m5:NC1CCN(CC1)CC1=CC=CC=C1;m1_m2_m3_m5:C(C)N(CC)CC;m4:O, Reagents are:m1_m2_m3_m5:ClCCl, and Products are 0:C(C)(=O)NC1CCN(CC1)CC1=CC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Acetyl chloride (3.95 ml) was added dropwise to a stirred solution of 4-amino1-benzylpiperidine (10.0 g) and triethylamine (7.7 ml) in dry dichloromethane (100 ml) at 4° C. The mixture was allowed to reach ambient temperature and stirred for 16 hours. Water was then added, the organic phase separated and dried (MgSO4), and removal of the solvent by evaporation gave 4-acetylamino-1-benzylpiperidine, 10.23 g, as a light brown solid which was used without further purification: NMR (CDCl3) δ 7.29(5H,m), 5.29(1H,b), 3.79(1H,m), 3.49(2H,s), 2.80(2H,dm), 2.12(2H,dt), 1.95(3H,s), 191(2H,dm), 1.46(2H,dq); m/e 233 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m5_m1_m2_m6:C(C)(=O)NC1CCN(CC1)CC1=CC=CC=C1;m5_m1_m2_m6:Cl;m3:[H][H];m4:C, Reagents are:m5_m1_m2_m6:[Pd];m5_m1_m2_m6:CO, and Products are 0:Cl.C(C)(=O)NC1CCNCC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 10% w/w Palladium on charcoal (1.5 g) was added to a solution of the product from step (i) (10.0 g), 1 molar hydrochloric acid (21.5 ml) and methanol (150 ml) and the mixture hydrogenated at room temperature and pressure until the theoretical amount of hydrogen had been taken up. Charcoal was added, the mixture stirred for 1 hour then filtered through diatomaceous earth and the filtrate evaporated to dryness giving 4-acetylaminopiperidine hydrochloride, 8.64 g, as a sticky foam: NMR (CDCl3 +d6DMSO). δ 9,72(1H,b), 9.02(1H,b), 7.40(1H,bd), 3.87(1H,m), 3.30(2H,m), 2.81(2H,m), 1.86(4H,m), 1.80(3H,s); m/e 143 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4:Cl.C(C)(=O)NC1CCNCC1;m1_m2_m3_m4:Cl.ClC1=CC=NC=C1;m1_m2_m3_m4:C(O)([O-])=O.[Na+], Reagents are:m1_m2_m3_m4:CC(CCO)C, and Products are 0:C(C)(=O)NC1CCN(CC1)C1=CC=NC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of the product from step (ii) (1.79 g), 4-chloropyridine hydrochloride (1.50 g), sodium hydrogen carbonate (2.86 g) in 3-methyl 1-butanol (25 ml) was heated at reflux temperature for 16 hours. The cooled mixture was filtered and the filtrate concentrated in vacuo. Purification of the residue by flash chromatography on silica, eluting with methanol/dichloromethane (1:2 v/v) gave 4-acetylamino-1-(4-pyridyl)piperidine as a foam, 0.69 g: NMR(d6DMSO) δ 8.10(2H,d), 7.80(1H,bd), 6.80(2H,dd), 3.82(3H,m), 2.93(2H,dt), 1.78(3H,s), 1.77(2H,m), 1.33(2H,dq); m/e 220 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m1_m2:C(C)(=O)NC1CCN(CC1)C1=CC=NC=C1;m1_m2:Cl, Reagents are:, and Products are 0:O.Cl.Cl.Cl.NC1CCN(CC1)C1=CC=NC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: The product from step (iii) (0.52 g) in 1 molar hydrochloric acid (11.9 ml) was heated at 95° C. for 5 hours. The solvent was evaporated and the residue, on drying over potassium hydroxide in vacuo gave 4-amino-1-(4-pyridyl)piperidine trihydrochloride hydrate, 0.70 g as a light brown solid: m.p. >300° C.; NMR (d6DMSO) δ 8.28(4H,m), 7.22(2H,d), 4.27(2H,bd), 3.5 to 3.15(3H +H2O), 2.09(2H,m), 1.59(2H,dq); m/e 178(M+H)+ ; calculated for C10 H15N3. 3HCl. 0.75 H2O: C, 40.0; H, 6.5; N, 14.0. found: C, 40.4; H, 6.3; N, 13.5%. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:CC(C(=O)C1=CC=C(OCC(=O)OC)C=C1)(C)Br;m1_m2_m3:N1=CC=C(C=C1)N1CCNCC1, Reagents are:m1_m2_m3:C(C)#N, and Products are 0:N1=CC=C(C=C1)N1CCN(CC1)C(C(=O)C1=CC=C(OCC(=O)OC)C=C1)(C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Methyl 4-(2,2-dimethylbromoacetyl)phenoxyacetate (1.58 g) was added to a stirred solution of 1-(4-pyridyl)piperazine (1.63 g) in acetonitrile (40 ml). After 34 days, the solid formed was removed by filtration and the filtrate evaporated to give an oil. Purification by flash chromatography on silica, eluting with 0.5 to 4.0% v/v methanol/dichloromethane gave the title compound, 240 mg, as a white foam: NMR (d6DMSO) δ 8.49 (2H, d), 8.12 (2H, d), 6.96 (2H, d), 6.77 (2H, d), 4.87 (2H, s), 3.69 (3H, s), 3.28 (4H, t), 2.58 (4H, t), 1.25 (6H, s); m/e 398 (M+H)+ ; calculated for C22H27N3O4.0.25H2O: C, 65.7; H, 6.8; N, 10.4. found: C, 65.3; H, 6.9; N, 10.4%. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:BrBr;m1_m2_m3:CC(C(=O)C1=CC=C(OCC(=O)OC)C=C1)C, Reagents are:m1_m2_m3:C(Cl)(Cl)(Cl)Cl, and Products are 0:BrC(C(=O)C1=CC=C(OCC(=O)OC)C=C1)(C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Bromine (2.09 ml) was added dropwise over ten minutes to a stirred solution of the product of step (i) above (9.44 g) in carbon tetrachloride (200 ml). The solution was stirred for 16 hours, then the solvent was evaporated in vacuo to give an orange oil. A solution of this oil, in a small volume of dichloromethane, was filtered through silica and the clear filtrate, on evaporation, gave methyl 4-(2-bromo-2,2-dimethylacetyl)phenoxyacetate, 11.3 g, as a white crystalline solid: m.p. 46°-50° C.; NMR (d6DMSO) δ 8.09 (2H, d), 7.05 (2H, d), 4.92 (2H, s), 3.72 (3H, s), 2.0(6H, s). |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:CC(C(=O)C1=CC=C(OCC(=O)OC)C=C1)(C)Br;m1_m2_m3:N1=CC=C(C=C1)N1CCNCC1, Reagents are:m1_m2_m3:C(C)#N, and Products are 0:N1=CC=C(C=C1)N1CCN(CC1)CC(C(=O)C1=CC=C(OCC(=O)OC)C=C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred mixture of methyl 4-(2,2-dimethylbromoacetyl)-phenoxyacetate (3.15 g), and 1-(4-pyridyl)piperazine (3.26 g) in acetonitrile (200 ml) was heated at reflux temperature for 4 days. The solvent was removed in vacuo and the residue partioned between dichloromethane/water. The organic phase was dried (MgSO4), evaporated and then purified by flash chromatography on silica, eluting with 2 to 5% v/v methanol/dichloromethane. Further purification by flash chromatography on neutral alumina, eluting with dichloromethane, gave the title compound, 350 mg, as a clear oil: NMR (d6DMSO) δ 8.12 (2H, d), 7.98 (2H, d), 7.04 (2H, d), 6.75 (2H, d), 4.9 (2H, s), 3.86 (1H,m), 3.71 (3H, s), 3.19 (4H, t), 2.70 (1H, q), 2.49 (DMSO+4H), 2.36 (1H, q), 1.09 (3H, s), trace of dichloromethane; m/e 398 (M+H)+ ; calculated for C22 H27N3O4.0.1 CH2Cl2 : C, 65.3; H, 6.7; N, 10.3. found: C, 65.1; H, 6.9; N, 10.1%. |
Here is a chemical reaction formula: Reactants are:m2_m4:BrCC1=CC=C(C=C1)CCCC(=O)OC;m1_m3:N1=CC=C(C=C1)N1CCNCC1, Reagents are:m2_m4:C(C)#N;m1_m3:C(C)#N, and Products are 0:N1=CC=C(C=C1)N1CCN(CC1)CC1=CC=C(C=C1)CCCC(=O)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: 1-(4-Pyridyl)piperazine (1.63 g) was dissolved in warm acetonitrile (25 ml), the solution cooled to 30° C. and with stirring, a solution of methyl 4-(4-bromomethylphenyl)butyrate in acetonitrile (5 ml) added. After 30 minutes the resulting precipitate was removed by filtration and the filtrate concentrated in vacuo to give a yellow oil. Purification by flash chromatography on silica, eluting with 0 to 4% v/v methanol/dichloromethane gave a solid. Trituration with ether and removal of the insoluble solid gave a clear solution. Concentration of this solution gave the title compound, 0.90 g, as a white fluffy solid: m.p. 126°-127° C.; NMR (d6DMSO) δ 8.14 (2H, d), 7.24 (2H, d), 7.14 (2H, d), 6.77 (2H, d), 3.59 (3H, s), 3.48 (2H, s), 3.30 (4H, t), 2.59 (2H, t), 2.47 (4H, t), 2.32 (2H, t), 1.63 (2H, m); m/e 354 (M+H)+ ; calculated for C21H27N3O2.0.25H2O: C, 70.4; H, 7.7; N, 11.7. found: C, 70.6; H, 7.6; N, 11.7%. |
Here is a chemical reaction formula: Reactants are:m1_m2:FC(C(=O)O)(F)F;m1_m2:N1=CC=C(C=C1)N(C(=O)OC(C)(C)C)C1=CC=C(OCCCCCC(=O)OCC)C=C1, Reagents are:m3:ClCCl, and Products are 0:N1=CC=C(C=C1)NC1=CC=C(OCCCCCC(=O)OCC)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Trifluoroacetic acid (3 ml) was added to a stirred solution of ethyl 6-[4-[N-(4-pyridyl)-N-tertiary-butyloxycarbonylamino]-phenoxy]hexanoate (260 mg) dissolved in dichloromethane (3 ml). After 18 hours the solvents were removed in vacuo and the residual gum dissolved in dichloromethane. This solution was treated with a saturated solution of sodium hydrogen carbonate. The organic phase was washed with water, dried and evaporated. Trituration of the residue with hexane gave the title compound, 120 mg, as a white solid: m.p. 104°-106° C.; NMR (CDCl3) δ 8.22 (2H, d), 7.12 (2H, d), 6.90 (2H, d), 6.64 (2H, dd), 5.82 (1H, s), 4.13 (2H, q), 3.97 (2H, t), 2.34 (2H, t), 1.80 (2H, m), 1.70 (2H, m), 1.53 (2H, m), 1.27 (3H, t); m/e 329 (M+H)+ ; calculated for C19 H24N2O3. 0.25H2O:C, 68.6; H, 7.4; N, 8.4. found: C, 68.8; H, 7.3; N, 8.2%. |
Here is a chemical reaction formula: Reactants are:m1_m2:Cl.ClC1=CC=NC=C1;m1_m2:COC1=CC=C(N)C=C1, Reagents are:m3:ClCCl, and Products are 0:N1=CC=C(C=C1)NC1=CC=C(C=C1)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A stirred mixture of 4-chloropyridine hydrochloride (2 g) and 4-methoxyaniline (4.9 g) was heated at 140° C. for 5 hours. After cooling the residue was dissolved in dichloromethane (250 ml), the solution extracted with water (2×100 ml). The aqueous extracts were treated with sodium hydroxide solution and then extracted with ethyl acetate (4×100 ml). The combined organic extracts were washed with water, and saturated sodium chloride solution, then dried and the solvent evaporated. Purification by flash chromatography on silica, eluting with 10% v/v methanol/dichloromethane gave 4-(4-pyridylamino)-methoxybenzene, 2 g, as a fawn solid: m.p. 159°-160° C.; NMR (d6DMSO) δ8.47 (1H, s), 8.09 (2H, d), 7.10 (2H, d), 6.92 (2H, d), 6.70 (2H, dd), 3.73 (3H, s); m/e 201 (M+H)+ ; calculated for C12H12 N2O3 : C, 72.0; H, 6.0; N, 14.0. found: C, 71.4; H, 6.1; N, 13.8%. |
Here is a chemical reaction formula: Reactants are:m3:BrCCCCCC(=O)OCC;m1_m2_m4:[H-].[Na+];m1_m2_m4:N1=CC=C(C=C1)N(C(=O)OC(C)(C)C)C1=CC=C(C=C1)O, Reagents are:m1_m2_m4:CN(C)C=O, and Products are 0:N1=CC=C(C=C1)N(C(=O)OC(C)(C)C)C1=CC=C(OCCCCCC(=O)OCC)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Sodium hydride (50% w/w dispersion in mineral oil, 55 mg) was added under argon to a stirred solution of the product from step (iii) above (300 mg) in dry DMF (5 ml). After five minutes, ethyl 6-bromohexanoate (0.20 ml) was added and the mixture stirred for 16 hours. The DMF was evaporated in vacuo and the residue partitioned between dichloromethane and water. The aqueous phase was extracted with further dichloromethane. The combined organic extracts were washed with water then dried, and evaporated. The residue was purified by chromatography on alumina, eluting with dichloromethane and then 1% v/v methanol/dichloromethane. Evaporation of the appropriate fractions gave ethyl 6-[4-[N-(4-pyridyl)-N-tertiary-butyloxycarbonylamino]phenoxy]hexanoate, 260 mg, as a yellow gum: NMR (CDCl3) δ 8.40 (2H, dd), 7.16 (2H, dd), 7.07 (2H, m), 6.90 (2H, m), 4.13 (2H, q), 3.98 (2H, t), 2.34 (2H, t), 1.78 (4H, m), 1.57 (2H, m), 1.44 (9H, s), 1.26 (3H, t); m/e 429 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m6_m3_m5_m4:CN(C)C(=[N+](C)C)ON1C2=C(C=CC=C2)N=N1.F[P-](F)(F)(F)(F)F;m6_m3_m5_m4:C(C)(C)N(CC)C(C)C;m6_m3_m5_m4:CN(C)C=O;m1_m2:N1=CC=C(C=C1)C1N(CCNC1)C1=CC=C(C(=O)O)C=C1;m1_m2:C=1C=CC2=C(C1)N=NN2O, Reagents are:m6_m3_m5_m4:O, and Products are 0:N1=CC=C(C=C1)C1N(CCNC1)C1=CC=C(C(=O)N(CC(=O)OCC)C)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a stirred mixture of 4-[(4-pyridyl)piperazin-1-yl]benzoic acid (prepared as in Example 30(i)) (311 mg), HOBt.H2O (170 mg) and HBTU (416 mg) in DMF (5 ml) at 0°-5° C. under argon was added diisopropylethylamine (0.75 ml). The ice-bath was removed and the reaction mixture was stirred at room temperature for 15 minutes before solid sarcosine, ethyl ester hydrochloride (154 mg) was added. The reaction mixture was stirred at room temperature under argon overnight then diluted with dichloromethane (30 ml) and water (30 ml). The organic layer was separated and the aqueous layer was re-extracted with dichloromethane (30 ml). The combined organic extracts were washed with water, saturated sodium bicarbonate solution, water, dried (MgSO4) and evaporated. The residue was purified by filtration through a short bed of activated (grade II) alumina by elution with ethyl acetate/methanol, 5:1, to give ethyl N-(4-[(4-pyridyl)piperazin-1-yl]benzoyl)-N-methylglycinate (92 mg) as an amorphous solid: NMR (d6 -DMSO+CD3CO2D) δ 1.18 (3H, t), 2.98 (3H, s), 3.44 (4H, m), 3.79 (4H, m), 4.11 (4H, m), 6.94 (2H, d), 7.12 (2H, d), 7.31 (2H, br, d), 8.19 (2H, d); m/Z 383 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m1_m3_m2:NC1=CC=C(C=C1)N1CCN(CC1)C1=CC=NC=C1;m1_m3_m2:C1(CCC(=O)O1)=O;m1_m3_m2:CN(C)C=O, Reagents are:, and Products are 0:O=C(CC(C(=O)O)N)C1=CC=C(C=C1)N1CCN(CC1)C1=CC=NC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 1-(4-aminophenyl)-4-(4-pyridyl)piperazine (100 mg) in DMF (8 ml) was added succinic anhydride (79 mg). The reaction mixture was stirred at room temperature for 2.5 hr and a precipitate was collected, washed with DMF and ethanol, then dried to give the title compound (106 mg) as a beige-coloured solid: m.p. 263°-264° C.; NMR (d6 -DMSO+CF3CO2H) δ 2.68 (4H, m), 3.80 (4H, m), 4.19 (4H, m), 7.20 (2H, d), 7.56 (2H, d), 7.82 (2H, d), 8.21 (2H, d), 9.62 (1H, s); m/Z 355 (M+H)+ ; calculated for C19H22N4 O3. 0.4 H2O: C, 63.1%; H, 6.36%; N, 15.5%; found: C, 63.1%; H, 6.4%; N, 15.7%. |
Here is a chemical reaction formula: Reactants are:m1_m2:N1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(OCCCC(=O)O)C=C1;m1_m2:CO;m3:Cl.N1=CC=CC=C1, Reagents are:m4:C(C)(=O)OCC, and Products are 0:Cl.N1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(OCCCC(=O)O)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of the product from Example 26 (1.5 g) and methanol (80 ml) was heated to reflux with stirring, and solid pyridine hydrochloride (0.5 g) was added. Heating was stopped and ethyl acetate (10 ml) was added. The reaction mixture was evaporated until a slight turbidity was observed. On further cooling, a precipitate formed which was collected, washed with ethyl acetate and dried to give the title compound (1.33 g) as a beige solid: m.p.>240° C. (dec); NMR (d6 -DMSO) δ 1.90 (2H, m), 2.36 (2H, t), 3.17 (4H, m), 3.83 (4H, m), 3.91 (2H, t), 6.89 (4H, q), 7.26 (2H, d), 8.25 (2H, d), 12.1 (1H, br), 13.75 (1H, br); m/Z 342 (M+H)+ ; calculated for C19H23N3O3. 1.0 HCl: C, 60.4%; H, 6.4%; N, 11.1%; found: C, 60.0%; H, 6.4%, N, 10.8%. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4_m5:N1(C(CNCC1)=O)CC(=O)C1=CC=C(OCC(=O)OC)C=C1;m1_m2_m3_m4_m5:Cl.ClC1=CC=NC=C1;m1_m2_m3_m4_m5:C(C)N(CC)CC, Reagents are:m1_m2_m3_m4_m5:O;m1_m2_m3_m4_m5:O1CCOCC1, and Products are 0:Cl.N1=CC=C(C=C1)N1CC(N(CC1)CC(=O)C1=CC=C(OCC(=O)O)C=C1)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of methyl 4-[2-(piperazin-2-one-1-yl)acetyl]-phenoxyacetate (0.347 g), 4-chloropyridine hydrochloride (0.19 g) and triethylamine (0.178 g) in water (8 ml) and dioxan (1 ml) was heated on a steam bath for 2 hours and then evaporated to dryness. The residue was triturated with water (2 ml) and filtered. The solid thus obtained was recrystallised from water to give the title compound (0.187 g), m.p. 275°-277° C.; NMR(d6DMSO δ 8.33(2H,d), 8.0(2H,d), 7.21(2H,d), 7.1(2H,d), 4.97(2H,s), 4.81(2H,s), 3.94(2H,m), 3.59(2H,m); m/e 370(H+H)+ ; calculated for C19H20N3O5Cl. 0.75 H2O: C, 54.4; H, 5.0; N, 10.0. Found: C, 54.5; H, 5.3; N, 9.5%. |
Here is a chemical reaction formula: Reactants are:m2:[H-].[Na+];m3:C(C)OC(CC(CBr)C)=O;m1_m4:N1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(C=C1)O, Reagents are:m1_m4:CN(C)C=O, and Products are 0:CC(CC(=O)OCC)COC1=CC=C(C=C1)N1CCN(CC1)C1=CC=NC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a stirred suspension of 4-[4-(4-pyridyl)piperazin-1-yl]phenol (1.02 g) in dry DMF (10 ml) was added sodium hydride (60% dispersion in mineral oil, 0.16 g) and the mixture stirred for 1 hour at room temperature. To the resulting solution was added ethyl-4-bromo-3-methylbutyrate and the mixture stirred for 16 hours. Solvent was evaporated and the residue partitioned between water and dichloromethane. Insoluble material was removed by centrifugation. The organic layer was filtered through phase separating paper (Whatman IPS) and the residue was purified by flash chromatography on silica gel by elution with methanol/dichloromethane/concentrated ammonia (50/950/5) to give ethyl 3-methyl-4-[4-[4-(4-pyridyl)piperazin-1-yl]phenoxy]butyrate (0.27 g) which was hydrolysed in methanol (3 ml) and aqueous sodium hydroxide (1N, 2 ml) for 2 hours at room temperature. The solution was evaporated and the residue purified by reverse phase h.p.l.c (water/acetonitrile/0.1% TFA gradient) to give a glass which crystallised on trituration with ether to give the title compound (0.08 g): m.p. 169°-171° C.; NMR(d6DMSO) δ 13.45(1H,broad), 2.07(1H,broad) 8.27(2H,d), 7.28(2H,d), 6.9(4H,m), 3.80(6H,m), 3.16(4H,t), 2.45(1H,m), 2.37(1H,m), 2.12(1H,m), 1.0(3H,d); m/e 356(M+H)+ ; calculated for C22 H25N3O4F3. 0.5 H2O: C, 55.2; H, 5.6; N, 8.9. Found: C, 55.3; H, 5.6; N, 8.7%. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C(=C)C1CC(=O)OC1;m1_m2_m3:C(C)(=O)[O-].[Na+];m1_m2_m3:CO, Reagents are:, and Products are 0:OCC(CC(=O)OC)C=C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of RS 3-vinylbutyrolactone (3.5 g) and sodium acetate (2.56 g) in methanol (30 ml) was kept for 20 hours. Solvent was evaporated and the residue was partitioned between water and ether. The aqueous layer was extracted twice more with ether and the extracts combined, filtered through phase separating paper and evaporated. The residue was purified by filtration chromatography on silica gel (Merck 7736) starting with 1/9 ethyl acetate/hexane and progressing to 4/6 ethyl acetate/hexane as eluent to give methyl 4-hydroxy-3-vinylbutyrate as an oil; NMR(CDCl3) δ 5.73(1H,m), 5.15(2H,m), 3.68(3H,s), 3.60(2H,t), 2.76(1H,m), 2.48(2H,m), 1.69(1H,t); m/e 145(M+H)+. |
Here is a chemical reaction formula: Reactants are:m2_m6:N1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(C=C1)O;m4:N(=NC(=O)OCC)C(=O)OCC;m5:COC(CC(CO)C=C)=O;m3:C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1, Reagents are:m2_m6:ClCCl, and Products are 0:[OH-].[NH4+];0:N1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(OCC(CC(=O)OC)C=C)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a stirred suspension of 4-[4-(4-pyridyl)piperazin-1-yl]phenol (1.98 g) in dichloromethane (30 ml) at 15° C. was added triphenylphosphine (2.04 g) followed by dropwise addition of diethyl azodicarboxylate (1.35 g). The mixture was stirred until complete solution was obtained. Methyl-4-hydroxy-3-vinylbutyrate (1.12 g) was added dropwise and the mixture stirred for 4 hours. The solid which had precipitated during the reaction was the starting phenol and was filtered off. The filtrate was evaporated and the residue treated with ethyl acetate (20 ml) and filtered. The filtrate was extracted with 2N hydrochloric acid (2×10 ml) and the aqueous layer separated and basified with 0.89 S.G. ammonium hydroxide. The precipitate was extracted twice into ethyl acetate and the combined extracts filtered through phase separating paper and evaporated. The residue was purified by flash chromatography on silica gel, eluting with methanol/dichloromethane/0.89 S. G. ammonium hydroxide v:v:v 7.5/92.5/0.75 to give RS methyl 4-[4-[4-(4-pyridyl)piperazin-1-yl]-phenoxy]-3-vinylbutyrate (0.29 g); NMR(CDCl3) δ 8.3(2H,d), 6.88(4H,m), 6.70(2H,d), 5.85(1H,m), 5.20(2H,m), 3.90(2H,m), 3.67(3H,s), 3.48(2H,m), 3.18(2H,m), 3.06(1H,m), 2.68(1H,m), 2.47(1H,m), 1.80(1H,br); m/e 382 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m1_m2:C(C=C)OC1=CC=C(C=C1)N1CCN(CC1)C1=CC=NC=C1;m1_m2:C1(=CC=CC=C1)OC1=CC=CC=C1, Reagents are:m3:CCOCC, and Products are 0:C(C=C)C1=C(C=CC(=C1)N1CCN(CC1)C1=CC=NC=C1)O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: The product from step (i) (5 g) was heated under argon in gently refluxing diphenyl ether (15 g) for 21/2 hours. The mixture was cooled to room temperature and ether (70 ml) was added. The solid material was filtered and purified by flash chromatography on silica gel, eluting with methanol/dichloromethane (1/4 v/v) to give 2-allyl-4-[4-(4-pyridyl)piperazin-1-yl]phenol (0.88 g) as a solid, m.p. 180°-182° C.; NMR (d6 -DMSO) δ 8.88(1H,s), 8.19(2H,dd), 6.87(2H,dd), 6.7(3H,m), 5.88-6.03(1H,m), 5.0(2H,m), 3.44(4H,t), 3.28(2H,d), 3.05(4H,t); m/e 296 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m2:[H][H];m1:C(C=C)C1=C(C=CC(=C1)N1CCN(CC1)C1=CC=NC=C1)O, Reagents are:m4:Cl;m3:C(C)O;m5:[Pd], and Products are 0:C(CC)C1=C(C=CC(=C1)N1CCN(CC1)C1=CC=NC=C1)O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: The product from Example 134, step (ii) (0.74 g) in ethanol (25 ml) and 1N hydrochloric acid (2.5 ml) was hydrogenated at room temperature and atmospheric pressure over 10% palladium charcoal (0.15 g) until uptake of hydrogen was complete. Catalyst was removed by filtration through diatomaceous earth and the filtrate evaporated. The residue was triturated with a mixture of ethyl acetate (25 ml) and saturated sodium bicarbonate solution (25 ml) and the insoluble solid was filtered and washed with water and ethyl acetate. The aqueous layer of the filtrate was extracted twice with dichloromethane and the combined organic extracts evaporated. The residue was combined with the ethyl acetate-insoluble material and treated with boiling ethanol (40 ml), unsoluble material being removed by filtration. Evaportion of the filtrate gave 2-n-propyl-4-[4-(4-pyridyl)piperazin-1-yl]phenol (0.7 g) as a solid NMR (d6DMSO) δ 8.84-8.68(1H,m), 8.18(2H,d), 6.82(2H,m), 6.7(3H,m), 4.1(1H,m), 3.42(4H,t), 3.17(3H,s), 3.05(4H,t), 2.48(DMSO), 1.55(2H,m), 0.89(3H,t). |
Here is a chemical reaction formula: Reactants are:m1_m2:C(C)(C)(C)OC(=O)NC(C(=O)OC)CCOC1=CC=C(C=C1)N1CCN(CC1)C1=CC=NC=C1, Reagents are:m1_m2:C(=O)(C(F)(F)F)O, and Products are 0:NC(C(=O)OC)CCOC1=CC=C(C=C1)N1CCN(CC1)C1=CC=NC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: The compound of Example 140 (0.96 g) in TFA (10 ml) was kept at room temperature for 2 hours. The solution was evaporated and the residue dissolved in water (15 ml) and the solution basified with sodium carbonate. The mixture was extracted three times with dichloromethane. Evaporation of the combined extracts gave the title compound (0.56 g); m.p. 125°-127° C.; NMR(d6DMSO) δ 8.2(2H,d), 6.92(6H,m), 4.0(2H,m), 3.64(3H,s), 3.46(4H,t), 3.15(4H,t), 2.04(2H,m), 1.84(1H, m); m/e 371(M+H)+. Calculated for C20H26N4 O3. 0.75 H2O: C, 62.5; H, 7.17; N, 14.6. Found: C, 62.8; H, 6.8; N, 14.3%. |
Here is a chemical reaction formula: Reactants are:m2_m3:S(=O)(Cl)Cl;m2_m3:C(C)O;m1:N1=CC=C(C=C1)N1CC(N(CC1)CC(=O)C1=CC=C(OCC(=O)O)C=C1)=O, Reagents are:, and Products are 0:N1=CC=C(C=C1)N1CC(N(CC1)CC(=O)C1=CC=C(OCC(=O)OCC)C=C1)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A crude sample of the product of Example 36 (3.4 g) was treated with a solution, at 0° C., made by adding thionyl chloride (2.25 g) dropwise to ethanol (45 ml) with stirring at below 0° C. The mixture was stirred at room temperature for 2 hours, heated at gentle reflux for 21/2 hours, and evaporated. The residue was treated with water and adjusted to pH6 with aqueous sodium bicarbonate solution. The gum which precipitated was separated and the aqueous solution was adjusted to pH8 and extracted with dichloromethane, (2×50 ml). The combined extracts were washed with brine, dried and evaporated. The residue was purified by chromatography using a 10 g. Mega Bond Elut silica gel column, eluting with 5% methanol/dichloromethane/0.5% triethylamine to give the title product as a solid (0.2 g); m.p. 163°-165° C.; NMR(CDCl3) δ 8.34(2H,m), 7.97(2H,m), 6.98(2H,m), 6.63(2H,m), 4.89(2H,s), 4.7(2H,s), 4.29(2H,q), 4.1(2H,s), 3.7(2H, m), 3.6(2H,m), 1.31(3H,t); m/e 398(M+H)+ ; calculated for C21H23N3 O5 : C, 63.5; M, 5.83; N, 10.6. Found: C, 61.5; H, 5.9; N, 10.5%. |
Here is a chemical reaction formula: Reactants are:m4:C([O-])([O-])=O.[Na+].[Na+];m2:Br;m3:O;m1_m5:C(C1=CC=CC=C1)C1CC(=O)OC1;m1_m5:C(C)O, Reagents are:, and Products are 0:C(C1=CC=CC=C1)CC(CC(=O)OCC)Br, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of RS 3-benzylbutyrolactone (1.14 g) in ethanol (20 ml) was stirred at 5° C. and gassed for 4 hours with a slow stream of hydrogen bromide. The solution was kept at 5° C. for 20 hours and water (70 ml) added followed by sodium carbonate to neutralise the acid. The mixture was extracted with ethyl acetate and the organic layer filterd through phase separating paper and evaporated to give ethyl 4-benzyl-3-bromobutyrate as an oil; NMR(CDCl3) δ 7.24(5H,m), 4.13(2H,q); 3.45(2H,m), 2.62(2H,d), 2.44(3H,m), 1.25(3H,t); m/e 285(M+H)+. |
Here is a chemical reaction formula: Reactants are:m4:C(C1=CC=CC=C1)OC1=CC=C(C=C1)Br;m3:[H-].[K+];m2_m5:N1=CC=C(C=C1)N1CC(NCC1)=O, Reagents are:m6_m7:O;m6_m7:[Cl-].[Na+].O;m8:[Cu]I;m2_m5:CN(C=O)C, and Products are 0:N;0:C(C1=CC=CC=C1)OC1=CC=C(C=C1)N1C(CN(CC1)C1=CC=NC=C1)=O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a stirred suspension of 4-(4-pyridyl) piperazin-2-one (880 mg) in dimethyl formamide (20 ml) was added potassium hydride (1.0 ml of a 20% dispersion) and the mixture stirred for 0.5 hr, after which time was added copper (I) iodide (1.0 g). After 0.25 hr there was added 4-benzyloxybromobenzene (1.2 g) and the mixture stirred at 140° C. in an argon atmosphere for 2 hr. The reaction mixture was diluted with water and brine and extracted with dichloromethane (3×40 ml); the combined extracts were washed with water and brine, dried (PS paper) and evaporated to give crude product as a pasty solid (2.0 g). This was purified by flash chromatography on silica, eluting with dichloromethane/methanol/conc. ammonia (97:2.5:0.5 v/v) to give 4-benzyloxy [4-(4-pyridyl)piperazin-2-one-1-yl]benzene as a colourless solid (1.1 g) NMR δ (d6DMSO): 3.7-3.9 (4H,m); 4.1 (2H,s); 5.1 (2H,s); 6.85 (2H,d); 7.05 (2H,d); 7.25 (2H,d); 7.3-7.6 (5H,m); 8.2 (2H,d); m/e 360 (M+H)+. |
Here is a chemical reaction formula: Reactants are:m1_m2_m4:[H-].[Na+];m1_m2_m4:N1=CC=C(C=C1)N1CCN(CC1)C1=CC=C(C=C1)O;m3:C[C@H](CC(=O)OC(C)(C)C)COS(=O)(=O)C1=CC=C(C=C1)C, Reagents are:m1_m2_m4:CN(C)C=O, and Products are 0:C[C@H](CC(=O)OC(C)(C)C)COC1=CC=C(C=C1)N1CCN(CC1)C1=CC=NC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Sodium hydride (60% dispersion in mineral oil, 2.44 g) was added to a stirred suspension of 4-[4-(4-pyridyl)piperazin-1-yl]phenol (15.5 g) in dry DMF (120 ml) and the mixture was stirred for 45 minutes at room temperature. tert-Butyl (3R)-3-methyl-4-(p-toluene-sulphonyloxy)butyrate (20 g) was added and the mixture was stirred at room temperature for 20 hours. The mixture was evaporated and the residue was partitioned between dichloromethane and water. The organic layer was washed with water, filtered through phase separating paper (Whatman IPS) and evaporated. The residue was triturated under diethyl ether. The solid so obtained was recrystallised from ethyl acetate to give tert-butyl (3R)-3-methyl-4-[4-[4-(4-pyridyl)piperazin-1-yl]phenoxy]butyrate (10.6 g), m.p. 112°-113° C.; [alpha]D =-5.5° (conc.=1 g/100 ml of methanol; 20° C.); NMR (CDCl3) δ 8.3(2H,d), 6.89(4H,m), 6.7(2H,m), 3.79(2H,d), 3.46(4H,m), 3.28(4H,m), 2.31-2.53(2H,m), 2.08.2.21(1H,m), 1.44(9H, s), 1.07(3H,d). |
Here is a chemical reaction formula: Reactants are:m1_m2:C[C@H](CC(=O)OC(C)(C)C)C(=O)[O-];m1_m2:C1CCOC1, Reagents are:m3:CO, and Products are 0:OC[C@@H](CC(=O)OC(C)(C)C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: Borane-dimethyl sulphide complex (10M, 10.3 ml) was added during 15 minutes to a stirred mixture of 1-tert-butyl (3R)-3-methylsuccinate (12.9 g) and THF (200 ml) which had been cooled to -10° C. and placed under an atmosphere of argon. The mixture was stirred at -10° C. for 30 minutes. The mixture was allowed to warm to room temperature and was stirred for 1 hour. The mixture was recooled to 5° C. and methanol (50 ml) was added portionwise. The mixture was allowed to warm to room temperature and was stirred for 30 minutes. The mixture was evaporated and the residue was partitioned between dichloromethane (100 ml) and water (100 ml). The organic phase was filtered through phase separating paper and evaporated to give tert-butyl (3R)-4-hydroxy-3-methylbutyrate as an oil (11 g); NMR(CDCl3) δ 3.55(2H,m), 2.1-2.4(3H,m), 1.46(9H,s), 0.98(3H,d). |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4:C1(=CC=C(C=C1)S(=O)(=O)Cl)C;m1_m2_m3_m4:OC[C@@H](CC(=O)OC(C)(C)C)C;m1_m2_m3_m4:C(C)N(CC)CC, Reagents are:m1_m2_m3_m4:ClCCl, and Products are 0:C[C@H](CC(=O)OC(C)(C)C)COS(=O)(=O)C1=CC=C(C=C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: p-Toluenesulphonyl chloride (13.2 g) was added portionwise to a stirred mixture of tert-butyl (3R)-4-hydroxy-3-methylbutyrate (11 g), triethylamine (21 ml) and dichloromethane (120 ml) and the mixture was stirred at room temperature for 20 hours. The mixture was washed in turn with water and with a dilute aqueous sodium carbonate solution. The organic solution was filtered through phase separating paper and evaporated to give tert-butyl (3R)-3-methyl-4-(p-toluenesulphonyloxy)-butyrate as an oil (20 g): NMR(CDCl3) δ 7.6(2H,d), 7.33(2H,d), 3.92(2H,d), 2.45(3H,s), 2.18.2.47(2H,m), 2.0-2.15(1H,m), 1.42(9H,s), 0.95(3H,d). |
Here is a chemical reaction formula: Reactants are:m4:[Cl-].[NH4+];m3:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1OC1=CC(=CC=C1)OC)Cl;m1_m5_m2:N1=C(C=CC=C1)CO;m1_m5_m2:[H-].[Na+], Reagents are:m1_m5_m2:CC(=O)N(C)C, and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1OC1=CC(=CC=C1)OC)OCC1=NC=CC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a stirred solution of pyridine-2-methanol (130 mg) in dimethylacetamide (0.5 ml) is added gradually with stirring sodium hydride (62.7% dispersion-type, 60 mg) under ice-cooling, and thereto is added 4-tert-butyl-N-{6-chloro-5-(3-methoxyphenoxy)pyrimidin-4-yl}benzenesulfonamide (100 mg). The mixture is reacted at 100° C. for 30 minutes, and cooled. The pH value of the mixture is adjusted to pH 8 with saturated aqueous ammonium chloride solution. The mixture is extracted with ethyl acetate, and the extract is washed, dried, and concentrated to dryness under reduced pressure. The residue is crystallized from ethyl acetate to give 4-tert-butyl-N-{5-(3-methoxyphenoxy)-6-(2-pyridinylmethoxy)pyrimidin-4-yl}benzenesulfonamide (110 mg) as crystals. |
Here is a chemical reaction formula: Reactants are:m1_m2:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1OC1=CC(=CC=C1)OC)Cl;m1_m2:NCCO;m3:Cl, Reagents are:, and Products are 0:Cl.NCCOC1=C(C(=NC=N1)NS(=O)(=O)C1=CC=C(C=C1)C(C)(C)C)OC1=CC(=CC=C1)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: After treating 4-tert-butyl-N-{6-chloro-5-(3-methoxyphenoxy)-pyrimidin-4-yl}benzenesulfonamide and 2-aminoethanol in the same manner as in Example 1, the precipitated crystals are converted into a hydrochloride thereof to give N-{6-(2-aminoethoxy)-5-(3-methoxyphenoxy)pyrimidin-4-yl}-4-tert-butylbenzenesulfonamide hydrochloride (Compound A). |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m4:Cl.NCCOC1=C(C(=NC=N1)NS(=O)(=O)C1=CC=C(C=C1)C(C)(C)C)OC1=CC(=CC=C1)OC;m1_m2_m3_m4:ClC1=NC=CC=N1;m1_m2_m3_m4:C([O-])([O-])=O.[K+].[K+];m1_m2_m3_m4:CC(=O)N(C)C, Reagents are:m5:[Cl-].[NH4+], and Products are 0:O.C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1OC1=CC(=CC=C1)OC)OCCNC1=NC=CC=N1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of Compound A (150 mg), 2-chloropyrimidine (61 mg), potassium carbonate (122 mg) and dimethylacetamide (1.5 ml) is heated with stirring at 100° C. for three days. The reaction solution is diluted with aqueous ammonium chloride solution, and extracted with ethyl acetate. The extract is washed and dried. The solvent is evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; chloroform/methanol=100:1) and further recrystallized from ethyl acetate/n-hexane to give 4-tert-butyl-N-[5-(3-methoxyphenoxy)-6-{2-(2-pyrimidinylamino)ethoxy}-pyrimidin-4-yl]benzenesulfonamide hydrate (135 mg) as crystals. |
Here is a chemical reaction formula: Reactants are:m1_m5_m2:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1OC1=CC(=CC=C1)OC)NCCO;m1_m5_m2:[H-].[Na+];m4:[Cl-].[NH4+];m3:ClC1=NC=CC=N1, Reagents are:m1_m5_m2:CC(=O)N(C)C, and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1OC1=CC(=CC=C1)OC)NCCOC1=NC=CC=N1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of Compound B (116 mg) obtained in Example 19-(1) in dimethylacetamide (2 ml) is added sodium hydride (60% dispersion-type, 33 mg), and thereto is added 2-chloropyrimidine (40 mg). The reaction solution is stirred at room temperature overnight, and the mixture is treated with saturated aqueous ammonium chloride solution, and extracted with ethyl acetate. The ethyl acetate layer is washed, dried, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; chloroform/methanol=20:1), and crystallized from chloroform/diisopropyl ether to give 4-tert-butyl-N-[5-(3-methoxyphenoxy)-6-{2-(pyrimidin-2-yloxy)ethylamino}pyrimidin-4-yl]benzenesulfonamide (125 mg) as crystals. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3_m5_m4:BrC=1C=NC(=NC1)OCCOC1=C(C(=NC=N1)N)C1=CC=C(C=C1)C;m1_m2_m3_m5_m4:C(C)(C)(CC)C1=CC=C(C=C1)S(=O)(=O)Cl;m1_m2_m3_m5_m4:[OH-].[K+];m1_m2_m3_m5_m4:C1(=CC=CC=C1)C, Reagents are:m1_m2_m3_m5_m4:S(=O)(=O)(O)[O-].C(CCC)[N+](CCCC)(CCCC)CCCC;m6:[Cl-].[NH4+], and Products are 0:C(C)(C)(CC)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=NC=C(C=C1)Br, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 6-[2-(5-bromopyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-amine (150 mg), 4-tert-amylbenzenesulfonyl chloride (184 mg), 96% potassium hydroxide (powder, 300 mg), tetrabutylammonium hydrogen sulfate (34 mg) and toluene (10 ml) is stirred at room temperature overnight. The mixture is diluted with saturated aqueous ammonium chloride solution, and extracted with ethyl acetate. The ethyl acetate layer is washed, dried, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; chloroform/ethyl acetate=5:1), and recrystallized from hexane/ethyl acetate to give 4-tert-amyl-N-{6-[2-(5-bromopyridin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzenesulfonamide (188 mg). |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1OC1=CC(=CC=C1)OC)OCCOC1=NC(=NC=C1)SC, Reagents are:m1_m2_m3:[Ni];m1_m2_m3:C(C)O, and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1OC1=CC(=CC=C1)OC)OCCOC1=NC=NC=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 4-tert-butyl-N-[5-(3-methoxyphenoxy)-6-{2-(2-methylthiopyrimidin-4-yloxy)ethoxy}pyrimidin-4-yl]benzenesulfonamide (250 mg), Raney-nickel (W-2) (2 g) and ethanol (5 ml) is stirred at room temperature overnight, and the mixture is refluxed for four hours. Raney-nickel is removed by filtration, and washed with ethanol and acetic acid. The filtrate is concentrated under reduced pressure, and the residue is extracted with ethyl acetate. The ethyl acetate layer is washed, dried, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; chloroform/methanol=10:1), and recrystallized from ethyl acetate/n-hexane to give 4-tert-butyl-N-[5-(3-methoxyphenoxy)-6-{2-(pyrimidin-4-yloxy)ethoxy}pyrimidin-4-yl]benzenesulfonamide (76 mg) as crystals. |
Here is a chemical reaction formula: Reactants are:m1_m4_m2_m3_m5:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1OC1=CC(=CC=C1)OC)OCCOC=1N=NC(=CC1)Cl;m1_m4_m2_m3_m5:C(C)N(CC)CC;m1_m4_m2_m3_m5:CO, Reagents are:m1_m4_m2_m3_m5:[C].[Pd];m1_m4_m2_m3_m5:O1CCCC1, and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1OC1=CC(=CC=C1)OC)OCCOC=1N=NC=CC1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 4-tert-butyl-N-[6-{2-(6-chloropyridazin-3-yloxy)ethoxy}-5-(3-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide (150 mg), 10% palladium-carbon (30 mg), triethylamine (52 mg), methanol (8 ml) and tetrahydrofuran (6 ml) is stirred at room temperature for five hours under hydrogen atmosphere (1 atm), and the mixture is filtered to remove the catalyst. The filtrate is concentrated to dryness under reduced pressure. The residue is treated with aqueous citric acid solution, and extracted with chloroform. The extract is washed, dried and evaporated to remove the solvent. The residue is recrystallized from ethyl acetate/diisopropyl ether to give 4-tert-butyl-N-[5-(3-methoxyphenoxy)-6-{2-(pyridazin-3-yloxy)ethoxy}pyrimidin-4-yl]benzenesulfonamide (111 mg) as crystals. |
Here is a chemical reaction formula: Reactants are:m3:C(O)([O-])=O.[Na+];m1_m2_m4:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1OC1=CC(=CC=C1)OC)OCCOC1=NC=C(C=N1)C(=C)OCC;m1_m2_m4:Cl, Reagents are:m1_m2_m4:CC(=O)C, and Products are 0:C(C)(=O)C=1C=NC(=NC1)OCCOC1=C(C(=NC=N1)NS(=O)(=O)C1=CC=C(C=C1)C(C)(C)C)OC1=CC(=CC=C1)OC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 4-tert-butyl-N-[6-{2-(5-(1-ethoxyethenyl)pyrimidin-2-yloxy)ethoxy}-5-(3-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide (1.022 g), 10% hydrochloric acid (1 ml) and acetone (20 ml) is reacted at room temperature for four hours. The pH value of the reaction solution is adjusted to pH 6 with aqueous sodium hydrogen carbonate solution, and the mixture is evaporated to remove the solvent. To the residue are added aqueous ammonium chloride solution and ethyl acetate, and the ethyl acetate layer is collected. The ethyl acetate layer is washed, dried, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; ethyl acetate/n-hexane=1:1~ethyl acetate), and recrystallized from ethyl acetate/n-hexane to give N-[6-{2-(5-acetylpyrimidin-2-yloxy)ethoxy}-5-(3-methoxyphenoxy)pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide (849 mg). |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C(C)(=O)C=1C=NC(=NC1)OCCOC1=C(C(=NC=N1)NS(=O)(=O)C1=CC=C(C=C1)C(C)(C)C)OC1=CC(=CC=C1)OC;m1_m2_m3:O1CCCC1;m1_m2_m3:C(C)(C)O;m5:[BH4-].[Na+];m4:[BH4-].[Na+], Reagents are:m6:O, and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1OC1=CC(=CC=C1)OC)OCCOC1=NC=C(C=N1)C(C)O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a mixture of N-[6-{2-(5-acetylpyrimidin-2-yloxy)ethoxy}-5-(3-methoxyphenoxy)pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide (756 mg), tetrahydrofuran (10 ml) and isopropyl alcohol (10 ml) is added with stirring sodium borohydride (48 mg) under ice-cooling, and the mixture is stirred for 40 minutes under ice-cooling. To the reaction solution is further added sodium borohydride (14 mg), and the mixture is stirred for 30 minutes. The mixture is diluted with water, and extracted with ethyl acetate. The ethyl acetate layer is washed, dried, and concentrated to dryness under reduced pressure. The residue is purified by silica gel column chromatography (solvent; chloroform/methanol=40:1~20:1), and recrystallized from ethyl acetate/n-hexane to give 4-tert-butyl-N-[6-{2-(5-(1-hydroxyethyl)pyrimidin-2-yloxy)ethoxy}-5-(3-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide (571 mg) as crystals. |
Here is a chemical reaction formula: Reactants are:m1_m3_m2:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1OC1=CC(=CC=C1)OC)OCCOC1=NC=C(C=N1)C(C)O;m1_m3_m2:S(=O)(Cl)Cl, Reagents are:m1_m3_m2:C(Cl)Cl, and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1OC1=CC(=CC=C1)OC)OCCOC1=NC=C(C=N1)CC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 4-tert-butyl-N-[6-{2-(5-(1-hydroxyethyl)pyrimidin-2-yloxy)ethoxy}-5-(3-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide (150 mg) in methylene chloride (3 ml) is added thionyl chloride (90 mg), and the mixture is reacted at room temperature for 0.5 hour. The reaction solution is concentrated to dryness under reduced pressure, and to the residue are added 10% palladium-carbon (30 mg), triethylamine (76 mg) and ethanol (3 ml), and the mixture is stirred at room temperature for two hours under hydrogen atmosphere (1 atm). The catalyst is removed by filtration, and the filtrate is concentrated to dryness under reduced pressure. The residue is extracted with ethyl acetate, and the ethyl acetate layer is washed, dried, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; chloroform/ethyl acetate=10:1), and recrystallized from ethyl acetate/n-hexane to give 4-tert-butyl-N-[6-{2-(5-ethylpyrimidin-2-yloxy)ethoxy}-5-(3-methoxyphenoxy)pyrimidin-4-yl]benzenesulfonamide (137 mg) as crystals. |
Here is a chemical reaction formula: Reactants are:m1_m2:BrC=1C=NC(=NC1)OCCOC1=C(C(=NC=N1)NS(=O)(=O)C1=CC=C(C=C1)C(C)(C)C)C1=CC=C(C=C1)C;m1_m2:C(C1=CC=CC=C1)=O, Reagents are:, and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=NC=C(C=N1)C(C1=CC=CC=C1)O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: N-[6-{2-(5-Bromopyrimidin-2-yloxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide and benzaldehyde are treated in the same manner as in Example 129 to give 4-tert-butyl-N-[6-{2-(5-(α-hydroxybenzyl)primidin-2-yloxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl]-benzenesulfonamide. |
Here is a chemical reaction formula: Reactants are:m3_m4_m8_m5:BrC1=CC=C(OCCOC2=C(C(=NC=N2)NS(=O)(=O)C2=CC=C(C=C2)C(C)(C)C)C2=CC=C(C=C2)C)C=C1;m3_m4_m8_m5:C(C)OC(=C)[Sn](CCCC)(CCCC)CCCC;m3_m4_m8_m5:O1CCOCC1;m6:[F-].[K+], Reagents are:m3_m4_m8_m5:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3.C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3.Cl[Pd]Cl;m7:C(C)(=O)OCC, and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=CC=CC=C1;0:C(C)(=O)C1=CC=C(OCCOC2=C(C(=NC=N2)NS(=O)(=O)C2=CC=C(C=C2)C(C)(C)C)C2=CC=C(C=C2)C)C=C1;0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=CC=C(C=C1)C(=O)OCC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of N-[6-{2-(4-bromophenoxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide (600 mg), (1-ethoxyvinyl)tributyltin (680 mg), bis(triphenylphosphine)palladium (II) chloride (35.5 mg) and dioxane (24 ml) is refluxed for 18 hours. The mixture is diluted with ethyl acetate, and thereto is added 10% aqueous potassium fluoride solution, and the precipitated crystals are removed by filtration. The filtrate is extracted with ethyl acetate, and the ethyl acetate layer is washed, dried, and concentrated to dryness under reduced pressure. The residue is purified by silica gel column chromatography (solvent; n-hexane/ethyl acetate=5:1~3:1~1:1), and the obtained compounds are each recrystallized from ethyl acetate/diisopropyl ether to give 4-tert-butyl-N-{5-(4-methylphenyl)-6-(2-phenoxyethoxy)pyrimidin-4-yl}benzenesulfonamide (Compound A) (42 mg), N-[6-{2-(4-acetylphenoxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl]-4-tert-butylbenzenesulfonamide (Compound B) (242 mg) and 4-tert-butyl-N-[6-{2-(4-ethoxycarbonylphenoxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl]benzenesulfonamide (Compound C) (58 mg), respectively. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=NC=C(C=C1)[N+](=O)[O-], Reagents are:m1_m2_m3:C(C)(C)O.O1CCCC1;m1_m2_m3:[C].[Pd], and Products are 0:NC=1C=CC(=NC1)OCCOC1=C(C(=NC=N1)NS(=O)(=O)C1=CC=C(C=C1)C(C)(C)C)C1=CC=C(C=C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 4-tert-butyl-N-{5-(4-methylphenyl)-6-{2-(5-nitropyridin-2-yloxy)ethoxy}pyrimidin-4-yl}benzenesulfonamide (975 mg) in isopropanol/tetrahydrofuran (1:1) (20 ml) is added 10% palladium-carbon (200 mg), and the mixture is stirred at room temperature for 1.5 hour under hydrogen atmosphere (1 atm). The catalyst is removed by filtration, and the filtrate is concentrated under reduced pressure. The residue is purified by silica gel column chromatography (solvent; chloroform/ethyl acetate=2:1), and recrystallized from ethyl acetate/n-hexane to give N-{6-{2-(5-aminopyridin-2-yl-oxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl}-4-tert-butylbenzenesulfonamide (829 mg) as crystals. |
Here is a chemical reaction formula: Reactants are:m3:Cl;m1_m4_m2_m5:NC=1C=CC(=NC1)OCCOC1=C(C(=NC=N1)NS(=O)(=O)C1=CC=C(C=C1)C(C)(C)C)C1=CC=C(C=C1)C;m1_m4_m2_m5:C(C1=CC=CC=C1)(=O)Cl, Reagents are:m1_m4_m2_m5:N1=CC=CC=C1;m1_m4_m2_m5:C(Cl)Cl, and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=C(C(=NC=N1)OCCOC1=CC=C(C=N1)NC(C1=CC=CC=C1)=O)C1=CC=C(C=C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of N-{6-{2-(5-aminopyridin-2-yloxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl}-4-tert-butylbenzenesulfonamide (150 mg) in pyridine (2 ml) is added a solution of benzoyl chloride (43 mg) in methylene chloride (0.4 ml), and the mixture is stirred at room temperature for two hours. To the reaction solution is added 10% hydrochloric acid, and the mixture is extracted with ethyl acetate. The ethyl acetate layer is washed, dried and evaporated to remove the solvent. The residue is recrystallized from ethyl acetate/n-hexane to give N-(6-[2-{6-(4-tert-butylphenylsulfonylamino)-5-(4-methylphenyl)pyrimidin-4-yloxy}ethoxy]pyridin-3-yl)benzamide (161 mg) as crystals. |
Here is a chemical reaction formula: Reactants are:m1_m2:NC=1C=CC(=NC1)OCCOC1=C(C(=NC=N1)NS(=O)(=O)C1=CC=C(C=C1)C(C)(C)C)C1=CC=C(C=C1)C;m1_m2:C(C)(=O)OC(C)=O, Reagents are:, and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=C(C(=NC=N1)OCCOC1=CC=C(C=N1)NC(C)=O)C1=CC=C(C=C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: N-{6-{2-(5-Aminopyridin-2-yloxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl}-4-tert-butylbenzenesulfonamide and acetic anhydride are treated in the same manner as in Example 135 to give N-[6-[2-{6-(4-tert-butylphenylsulfonylamino)-5-(4-methylphenyl)pyrimidin-4-yloxy}ethoxy]pyridin-3-yl]-acetamide. |
Here is a chemical reaction formula: Reactants are:m1_m2:NC=1C=CC(=NC1)OCCOC1=C(C(=NC=N1)NS(=O)(=O)C1=CC=C(C=C1)C(C)(C)C)C1=CC=C(C=C1)C;m1_m2:C(C(C)(C)C)(=O)Cl, Reagents are:, and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=C(C(=NC=N1)OCCOC1=CC=C(C=N1)NC(C(C)(C)C)=O)C1=CC=C(C=C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: N-{6-{2-(5-Aminopyridin-2-yloxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl}-4-tert-butylbenzenesulfonamide and pivaloyl chloride are treated in the same manner as in Example 135 to give N-[6-[2-{6-(4-tert-butylphenylsulfonylamino)-5-(4-methylphenyl)pyrimidin-4-yloxy}ethoxy]pyridin-3-yl]pivalamide. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=CC=C(C=C1)OCC1=CC=CC=C1, Reagents are:m1_m2_m3:[C].[Pd];m1_m2_m3:C(C)O.O1CCCC1, and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=CC=C(C=C1)O, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 4-tert-butyl-N-{6-[2-(4-benzyloxyphenoxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzensulfonamide (3.95 g), 10% palladium-carbon (1.5 g) and ethanol-tetrahydrofuran (80 ml-80 ml) is subjected to catalytic hydrogenation at room temperature under hydrogen atmosphere (1 atm) for 24 hours. The catalyst is removed by filtration, and the filtrate is concentrated. The residue is crystallized from ethyl acetate/diisopropyl ether to give 4-tert-butyl-N-{6-[2-(4-hydroxyphenoxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzenesulfonamide (3.31 g). |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=CC=C(C=C1)[N+](=O)[O-], Reagents are:m1_m2_m3:[C].[Pd];m1_m2_m3:C(C)O.O1CCCC1, and Products are 0:NC1=CC=C(OCCOC2=C(C(=NC=N2)NS(=O)(=O)C2=CC=C(C=C2)C(C)(C)C)C2=CC=C(C=C2)C)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 4-tert-butyl-N-{5-(4-methylphenyl)-6-[2-(4-nitrophenoxy)ethoxy]pyrimidin-4-yl}benzenesulfonamide (383 mg), 10% palladium-carbon (50 mg) and ethanol-tetrahydrofuran (6 ml-3 ml) is subjected to catalytic hydrogenation at room temperature under hydrogen atmosphere (1 atm) for two hours. The catalyst is removed by filtration, and the filtrate is concentrated. The residue is purified by silica gel column chromatography (solvent; chloroform/ethyl acetate=10:1), and recrystallized from ethyl acetate/diisopropyl ether to give N-{6-[2-(4-aminophenoxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}-4-tert-butylbenzenesulfonamide (358 mg). |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=CC=C(C=C1)C#N;m1_m2_m3:C(CCC)[Sn](CCCC)(CCCC)N=[N+]=[N-];m1_m2_m3:C1(=CC=CC=C1)C;m5_m4:[F-].[K+], Reagents are:m5_m4:C(C)(=O)OCC, and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=CC=C(C=C1)C1=NN=NN1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 4-tert-butyl-N-{6-[2-(4-cyanophenoxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzensulfonamide (1.31 g), tributyltin azide (1.60 g) and toluene (13 ml) is refluxed under argon atmosphere for 24 hours. After cooling, ethyl acetate and 10% aqueous potassium fluoride solution are added to the reaction solution. The insoluble materials are removed by filtration, and the ethyl acetate layer is concentrated to dryness under reduced pressure. To the residue are added 10% aqueous sodium hydroxide solution and diethyl ether, and the mixture is stirred at room temperature for 20 minutes. The aqueous layer is washed with diethyl ether, and acidified with 10% hydrochloric acid under ice-cooling. The mixture is extracted with ethyl acetate, and the ethyl acetate layer is washed, dried and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent:chloroform:methanol=100:0~20:1), and crystallized from ethyl acetate to give 4-tert-butyl-N-{5-(4-methylphenyl)-6-[2-(4-(5-tetrazolyl)phenoxy)ethoxy]-pyrimidin-4-yl}benzensulfonamide (1.26 g). |
Here is a chemical reaction formula: Reactants are:m1_m4_m2_m3:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=C(C(=NC=N1)OCCOC1=CC=C(OCC(=O)OC(C)(C)C)C=C1)C1=CC=C(C=C1)C;m1_m4_m2_m3:C1(=CC=CC=C1)OC;m1_m4_m2_m3:FC(C(=O)O)(F)F, Reagents are:m1_m4_m2_m3:ClCCl, and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=C(C(=NC=N1)OCCOC1=CC=C(OCC(=O)O)C=C1)C1=CC=C(C=C1)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of tert-butyl 4-{2-{6-(4-tert-butylbenzenesulfonylamino)-5-(4-methylphenyl)pyrimidin-4-yloxy]ethoxy}phenoxyacetate (1.25 g) in dichloromethane (120 ml) are added anisole (2.09 g) and trifluoroacetic acid (20 ml) under ice-cooling. The mixture is stirred at room temperature for five hours, washed with water, and extracted with 10% aqueous sodium hydroxide solution. The aqueous layer is washed with chloroform, and acidified with 10% hydrochloric acid under ice-cooling. The mixture is extracted with ethyl acetate, and the extract is washed, dried, and evaporated to remove the solvent. The residue is crystallized from ethyl acetate/diisopropyl ether to give 4-{2-[6-(4-tert-butylbenzenesulfonylamino)-5-(4-methylphenyl)pyrimidin-4-yl-oxy]ethoxy}phenoxyacetic acid (1.14 9). |
Here is a chemical reaction formula: Reactants are:m1_m4_m2:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=NC=C(C=N1)C=O;m1_m4_m2:[BH4-].[Na+];m3:[Cl-].[NH4+], Reagents are:m1_m4_m2:O1CCCC1.C(C)(C)O, and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=NC=C(C=N1)CO, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of 4-tert-butyl-N-[6-{2-(5-formylpyrimidin-2-yloxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl]benzenesulfonamide (143 mg) in tetrahydrofuran-isopropanol (4 ml-4 ml) is added sodium borohydride (13 mg) under ice-cooling, and the mixture is reacted for two hours. The mixture is treated with aqueous ammonium chloride solution, and extracted with ethyl acetate. The ethyl acetate layer is washed, dried, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; chloroform/methanol=200:1~50:1), and crystallized from diethyl ether to give 4-tert-butyl-N-[6-{2-(5-hydroxymethylpyrimidin-2-yloxy)ethoxy}-5-(4-methylphenyl)pyrimidin-4-yl]benzenesulfonamide (96 mg). |
Here is a chemical reaction formula: Reactants are:m1_m4:[H-].[Na+];m2_m5_m6:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC(=NC(=C1C1=CC=C(C=C1)C)OCCO)CCC;m3:ClC1=NC=C(C=N1)Br, Reagents are:m1_m4:O1CCCC1;m2_m5_m6:CC(=O)N(C)C;m2_m5_m6:O1CCCC1, and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC(=NC(=C1C1=CC=C(C=C1)C)OCCOC1=NC=C(C=N1)Br)CCC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a suspension of sodium hydride (0.25 g) in tetrahydrofuran (5 ml) is added dropwise a solution of 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(4-methylphenyl)-2-n-propylpyrimidin-4-yl]benzenesulfonamide (1.00 g) in dimethylacetamide (3 ml) and tetrahydrofuran (10 ml) at room temperature, and thereto is added 2-chloro-5-bromopyrimidine (0.56 g), and the mixture is stirred at room temperature for 2.5 hours. The reaction mixture is acidified with ice-cold diluted hydrochloric acid, and extracted with ethyl acetate. The extract is washed, dried, and evaporated to remove the solvent. The resulting oily product is purified by silica gel column chromatography (solvent; chloroform), and crystallized from n-hexane to give 4-tert-butyl-N-[6-{2-(5-bromopyrimidin-2-yloxy)ethoxy}-5-(4-methylphenyl)-2-n-propylpyrimidin-4-yl]benzenesulfonamide (1.21 g) as crystals. |
Here is a chemical reaction formula: Reactants are:m4:[F-].[K+];m1_m2_m6_m3:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC(=NC(=C1C1=CC=C(C=C1)C)OCCOC1=NC=C(C=N1)Br)CCC;m1_m2_m6_m3:S1C(=CC=C1)[Sn](CCCC)(CCCC)CCCC;m1_m2_m6_m3:O1CCOCC1, Reagents are:m5:C(C)(=O)OCC;m1_m2_m6_m3:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3.C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3.Cl[Pd]Cl, and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC(=NC(=C1C1=CC=C(C=C1)C)OCCOC1=NC=C(C=N1)C=1SC=CC1)CCC, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 4-tert-butyl-N-[6-{2-(5-bromopyrimidin-2-yloxy)ethoxy}-5-(4-methylphenyl)-2-n-propylpyrimidin-4-yl]benzenesulfonamide (300 mg), 2-thienyltributyltin (670 mg), bis(triphenylphosphine)palladium (II) chloride (16 mg) and dioxane (5 ml) is refluxed for 80 minutes. After cooling, the reaction solution is diluted with ethyl acetate, and thereto is added 10% aqueous potassium fluoride solution. The mixture is stirred at room temperature for one hour, and the reaction solution is washed, dried, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; n-hexane/ethyl acetate=30:1~10:1), and crystallized from methylene chloride/n-hexane to give 4-tert-butyl-N-[6-{2-(5-(2-thienyl)pyrimidin-2-yloxy)ethoxy}-5-(4-methylphenyl)-2-n-propylpyrimidin-4-yl]-benzenesulfonamide (209 mg) as crystals. |
Here is a chemical reaction formula: Reactants are:m1_m2_m5_m3:ClC1=C(C(=NC(=N1)C1=NC=CC=N1)NS(=O)(=O)C1=CC=C(C=C1)C(C)(C)C)OC1=C(C=CC=C1)OC;m1_m2_m5_m3:C(C)(=O)C1=CC=C(OCCO)C=C1;m1_m2_m5_m3:[H-].[Na+];m4:Cl, Reagents are:m1_m2_m5_m3:CC(=O)N(C)C, and Products are 0:C(C)(=O)C1=CC=C(OCCOC2=C(C(=NC(=N2)C2=NC=CC=N2)NS(=O)(=O)C2=CC=C(C=C2)C(C)(C)C)OC2=C(C=CC=C2)OC)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: To a solution of N-{6-chloro-2-(2-pyrimidyl)-5-(2-methoxyphenoxy)pyrimidin-4-yl}-4-tert-butylbenzenesulfonamide (1.05 g) and 2-(4-acetylphenoxy)ethanol (728 mg) in dimethylacetamide (12 ml) is added sodium hydride (240 mg) under ice-cooling, and the mixture is stirred at room temperature overnight. The reaction solution is acidified with 10% hydrochloric acid, and extracted with ethyl acetate. The extract is washed, dried, and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; chloroform/acetonitrile=2:1), and recrystallized from ethyl acetate/n-hexane to give N-[6-{2-(4-acetylphenoxy)ethoxy}-2-(2-pyrimidyl)-5-(2-methoxyphenoxy)pyrimidin-4-yl}-4-tert-butylbenzenesulfonamide (482 mg) as crystals. |
Here is a chemical reaction formula: Reactants are:m1_m2:ClC1=C(C(=NC(=N1)C1=NC=CC=N1)NS(=O)(=O)C1=CC=C(C=C1)C(C)(C)C)OC1=C(C=CC=C1)OC;m1_m2:BrC1=CC=C(OCCO)C=C1, Reagents are:, and Products are 0:BrC1=CC=C(OCCOC2=C(C(=NC(=N2)C2=NC=CC=N2)NS(=O)(=O)C2=CC=C(C=C2)C(C)(C)C)OC2=C(C=CC=C2)OC)C=C1, please give me the reaction condition of this formula. | The condition of this chemical reaction is: N-{6-Chloro-2-(2-pyrimidyl)-5-(2-methoxyphenoxy)pyrimidin-4-yl}-4-tert-butylbenzenesulfonamide and 2-(4-bromophenoxy)ethanol are treated in the same manner as in Example 192-(1) to give N-{6-{2-(4-bromophenoxy)ethoxy}-2-(2-pyrimidyl)-5-(2-methoxyphenoxy)pyrimidin-4-yl}-4-tert-butylbenzenesulfonamide. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=NC=C(C=N1)S(=O)C, Reagents are:m1_m2_m3:FC(C(=O)OC(C(F)(F)F)=O)(F)F;m1_m2_m3:C(Cl)Cl, and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=NC=C(C=N1)S, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A solution of 4-tert-butyl-N-{6-[2-(5-methylsulfinylpyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzenesulfonamide (471 mg) in trifluoroacetic anhydride (5 ml) and methylene chloride (5 ml) is refluxed for 30 minutes, and the mixture is evaporated to remove the solvent. The residue is dissolved in methanol/triethylamine (1:1) (20 ml), and concentrated to dryness under reduced pressure. The residue is dissolved in chloroform, washed with saturated aqueous ammonium chloride solution and brine, dried over sodium sulfate, and filtered. The filtrate is concentrated under reduced pressure to give 4-tert-butyl-N-{6-[2-(5-mercaptopyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzenesulfonamide as pale yellow foam (529 mg). |
Here is a chemical reaction formula: Reactants are:m1_m4_m5_m2:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=NC=C(C=N1)Br;m1_m4_m5_m2:CN1C(N(CC1)C)=O, Reagents are:m1_m4_m5_m2:[C-]#N.[Zn+2].[C-]#N;m1_m4_m5_m2:C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1;m3:[Cl-].[NH4+], and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=NC=C(C=N1)C#N, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 4-tert-butyl-N-{6-[2-(5-bromopyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzenesulfonamide (1.00 g), zinc cyanide (784 mg), tetrakis(triphenylphosphine)palladium (250 mg) and 1,3-dimethyl-2-imidazolidinone (40 ml) is stirred at 80° C. for 6 hours under argon atmosphere. The mixture is cooled to room temperature, and diluted with saturated aqueous ammonium chloride solution. The mixture is extracted with ethyl acetate, and the organic layer is washed with water (twice) and brine, dried over sodium sulfate, and filtered. The filtrate is concentrated under reduced pressure, and the residue is purified by silica gel column chromatography (solvent; chloroform/ethyl acetate=10:1) and recrystallized from tetrahydrofuran/ethyl acetate to give 4-tert-butyl-N-{6-[2-(5-cyanopyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzenesulfonamide (590 mg) as colorless crystalline powder. |
Here is a chemical reaction formula: Reactants are:m1_m2_m6_m7_m3_m4:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=NC=C(C=N1)Br;m1_m2_m6_m7_m3_m4:C[Si](C)(C)C#C;m1_m2_m6_m7_m3_m4:C(C)N(CC)CC;m1_m2_m6_m7_m3_m4:CN(C=O)C, Reagents are:m5:[Cl-].[NH4+];m1_m2_m6_m7_m3_m4:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3.C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3.Cl[Pd]Cl;m1_m2_m6_m7_m3_m4:[Cu]I, and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=NC=C(C=N1)C#C[Si](C)(C)C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 4-tert-butyl-N-{6-[2-(5-bromopyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzenesulfonamide (1.00 g), trimethylsilylacetylene (330 mg), bis(triphenylphosphine)palladium (II) chloride (58 mg), copper (I) iodide (32 mg), triethylamine (420 mg) and dimethylformamide (5 ml) is stirred at 50° C. for three hours under argon atmosphere, and cooled to room temperature. The mixture is diluted with saturated aqueous ammonium chloride solution, and extracted with ethyl acetate. The organic layer is washed with water and brine, and dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (solvent; chloroform/ethyl acetate=40:1), and recrystallized from ethyl acetate/n-hexane to give 4-tert-butyl-N-{6-[2-(5-trimethylsilylethynylpyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzenesulfonamide (837 mg) as colorless crystalline powder. |
Here is a chemical reaction formula: Reactants are:m1_m2_m3:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=NC=C(C=N1)C#C[Si](C)(C)C;m1_m2_m3:C([O-])([O-])=O.[K+].[K+];m1_m2_m3:CO, Reagents are:m4:[Cl-].[NH4+], and Products are 0:C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1C1=CC=C(C=C1)C)OCCOC1=NC=C(C=N1)C#C, please give me the reaction condition of this formula. | The condition of this chemical reaction is: A mixture of 4-tert-butyl-N-{6-[2-(5-trimethylsilylethynylpyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}benzenesulfonamide (667 mg), potassium carbonate (299 mg) and dry methanol (13 ml) is stirred at 0° C. for two hours, and diluted with saturated aqueous ammonium chloride solution, and extracted with ethyl acetate. The organic layer is washed with water and brine, dried over sodium sulfate, and filtered. The filtrate is concentrated under reduced pressure, and the residue is purified by silica gel column chromatography (solvent; chloroform/ethyl acetate=30:1) to give 4-tert-butyl-N-{6-[2-(5-ethynylpyrimidin-2-yloxy)ethoxy]-5-(4-methylphenyl)pyrimidin-4-yl}-benzenesulfonamide (502 mg) as colorless crystalline powder. |