3-methylbutan-2-ol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-fluoro-N-(5-isopropylpyridin-2-yl)benzenesulfonamide (203 mg, 0.690 mmol) and 3-methylbutan-2-ol (60.8 mg, 0.690 mmol) in toluene (3 mL) stirred in air at room temperature was added a solution of 2-tributylphosphoranylidene)acetonitrile (166 mg, 0.690 mmol) in toluene (0.5 mL). The reaction vessel was sealed and heated by microwaves to 150° C. for 30 minutes. After cooling, the solvent was evaporated in vacuo and the crude purified by mass directed autoprep (formic acid modifier) to give the title product (32 mg) as a colourless oil. LCMS (2 min, formic) Rt 1.41 min, m/z (ES+) 365 (M+H). The reaction vessel was sealed After cooling the solvent was evaporated in vacuo the crude purified by mass

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-fluoro-N-(5-isopropylpyridin-2-yl)benzenesulfonamide (203 mg, 0.690 mmol) and 3-methylbutan-2-ol (60.8 mg, 0.690 mmol) in toluene (3 mL) stirred in air at room temperature was added a solution of 2-tributylphosphoranylidene)acetonitrile (166 mg, 0.690 mmol) in toluene (0.5 mL). The reaction vessel was sealed and heated by microwaves to 150° C. for 30 minutes. After cooling, the solvent was evaporated in vacuo and the crude purified by mass directed autoprep (formic acid modifier) to give the title product (32 mg) as a colourless oil. LCMS (2 min, formic) Rt 1.41 min, m/z (ES+) 365 (M+H). The reaction vessel was sealed After cooling the solvent was evaporated in vacuo the crude purified by mass

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: DEAD (5.3 ml, 34.1 mmol) is slowly added to a solution of 4-Hydroxy-1H-indole-2-carboxylic acid ethyl ester 79 (5 g, 24.36 mmol), triphenylphosphine (8.95 g, 34.1 mmol) and 3-Methyl-butan-2-ol (3.58 ml, 33.13 mmol) in 50 ml of THF, so that the temperature always remained below 30° C. Stirring is continued for 3 days and the solvent is then evaporated. The crude mixture is purified by chromatography on silicagel using first cyclohexane as eluent, then increasing amounts of EtOAc (from 5% to 50%). the solvent is then evaporated The crude mixture is purified by chromatography on silicagel

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Crotonoyl chloride (21.35 g) in dichloromethane (100 mL) was charged into a 2-L reaction flask and cooled to 0° C. 3-Methyl-butan-2-ol (18 g) was added followed by diisopropylethylamine (31.7 g). The reaction mixture was aged at 0-10° C. for about 30 minutes and poured into dilute hydrochloric acid (33 g in 170 g water). Hexanes were added and the aqueous and organic layers were split. The organic layer was separated and subsequently purified via liquid chromatography to provide but-2-enoic acid 1,2-dimethyl-propyl ester (25.6 g). the aqueous and organic layers were split The organic layer was separated subsequently purified via liquid chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In 4 ml of tetrahydrofuran was suspended 0.10 g of sodium hydride (60% in oil), to which 0.5 ml of a solution containing 0.18 g of 3-methyl-2-butanol was added dropwise at 0° C., followed by stirring for 10 minutes. To this was added dropwise 0.5 ml of tetrahydrofuran containing 0.3 g of 4,6-dichloropyrimidine dissolved therein, followed by stirring at the same temperature for 4 hours. The reaction mixture was then poured into a saturated aqueous ammonium chloride solution, which was extracted three times with t-butyl methyl ether. The combined organic layers were washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel column chromatography to give 0.35 g of 4-chloro-6-(1,2-dimethylpropyloxy)pyrimidine. was added dropwise at 0° C. dissolved by stirring at the same temperature for 4 hours was extracted three times with t-butyl methyl ether The combined organic layers were washed with a saturated aqueous sodium chloride solution dried over anhydrous magnesium sulfate concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1,4-dibromo-n-butane (119.20 g, 0.0903 mol) in hexane (80 ml) was cooled at 0° C. with a sodium hydroxide aqueous solution (150 ml of solution prepared by mixing 75 g of sodium hydroxide and 150 ml of water) and tert-butylammonium bromide (4.4 mol %, 0.68 g, used as phase transfer catalyst), and a solution of 1,2-dimethylpropan-1-ol (1.27 g, 0.022 mol) in hexane (70 ml) was added dropwise over 1 h with vigorous mechanical stirring. The reaction mixture was allowed to warm to room temperature and left stirring for 2 h, the reaction mixture was then heated under reflux for 4 h. The organic layer was collected and dried (MgSO4) and the solvent was removed in vacuo. The crude oil was purified by column chromatography [DCM-petroleum fraction (bp 40-60° C.), 1:51] to give a colourless oil. left the reaction mixture was then heated under reflux for 4 h The organic layer was collected dried (MgSO4) the solvent was removed in vacuo The crude oil was purified by column chromatography [DCM-petroleum fraction (bp 40-60° C.), 1:51] to give a colourless oil

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1,4-dibromo-n-butane (119.20 g, 0.0903 mol) in hexane (80 ml) was cooled at 0° C. with a sodium hydroxide aqueous solution (150 ml of solution prepared by mixing 75 g of sodium hydroxide and 150 ml of water) and tert-butylammonium bromide (4.4 mol %, 0.68 g, used as phase transfer catalyst), and a solution of 1,2-dimethylpropan-1-ol (1.27 g, 0.022 mol) in hexane (70 ml) was added dropwise over 1 h with vigorous mechanical stirring. The reaction mixture was allowed to warm to room temperature and left stirring for 2 h, the reaction mixture was then heated under reflux for 4 h. The organic layer was collected and dried (MgSO4) and the solvent was removed in vacuo. The crude oil was purified by column chromatography [DCM-petroleum fraction (bp 40-60° C.), 1:51] to give a colourless oil. left the reaction mixture was then heated under reflux for 4 h The organic layer was collected dried (MgSO4) the solvent was removed in vacuo The crude oil was purified by column chromatography [DCM-petroleum fraction (bp 40-60° C.), 1:51] to give a colourless oil

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: DEAD (5.3 ml, 34.1 mmol) is slowly added to a solution of 4-Hydroxy-1H-indole-2-carboxylic acid ethyl ester 79 (5 g, 24.36 mmol), triphenylphosphine (8.95 g, 34.1 mmol) and 3-Methyl-butan-2-ol (3.58 ml, 33.13 mmol) in 50 ml of THF, so that the temperature always remained below 30° C. Stirring is continued for 3 days and the solvent is then evaporated. The crude mixture is purified by chromatography on silicagel using first cyclohexane as eluent, then increasing amounts of EtOAc (from 5% to 50%). the solvent is then evaporated The crude mixture is purified by chromatography on silicagel

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: DEAD (5.3 ml, 34.1 mmol) is slowly added to a solution of 4-Hydroxy-1H-indole-2-carboxylic acid ethyl ester 79 (5 g, 24.36 mmol), triphenylphosphine (8.95 g, 34.1 mmol) and 3-Methyl-butan-2-ol (3.58 ml, 33.13 mmol) in 50 ml of THF, so that the temperature always remained below 30° C. Stirring is continued for 3 days and the solvent is then evaporated. The crude mixture is purified by chromatography on silicagel using first cyclohexane as eluent, then increasing amounts of EtOAc (from 5% to 50%). the solvent is then evaporated The crude mixture is purified by chromatography on silicagel

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-methylbutan-2-ol (0.19 mL) in toluene (4 mL) was added sodium hydride (0.14 g), and the resulting mixture was stirred at 70° C. for 15 min under a nitrogen atmosphere. A mixture of tert-butyl 8-chloro-2,3-dihydropyrido[3,2-f][1,4]oxazepine-4(5H)-carboxylate (0.50 g), BINAP (0.033 g), Pd2(dba)3 (0.024 g) and toluene (4 mL) was added, and the resulting mixture was stirred at 100° C. for 2 hr under an argon atmosphere. The reaction solution was poured into water, and the resulting product was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (solvent gradient; 0→40% ethyl acetate/hexane) to give tert-butyl 8-(1,2-dimethylpropoxy)-2,3-dihydropyrido[3,2-f][1,4]oxazepine-4(5H)-carboxylate (0.36 g, 61%) as a yellow oil. was added the resulting mixture was stirred at 100° C. for 2 hr under an argon atmosphere the resulting product was extracted with ethyl acetate The organic layer was washed with water and saturated brine dried the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (solvent gradient; 0→40% ethyl acetate/hexane)