2-bromocyclohexan-1-one

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

実験手順: A mixture of 2-bromocyclohexanone (6.23 g, 0.035 mol) and urea (2.1 g, 0.035 mol) is refluxed in a solution of ammonium acetate (10 g), acetic acid (15 mL) and water (50 mL) for 4 h. Upon cooling slowly to room temp, white crystals form in the reaction vessel. The solid is collected by suction filtration, washed thoroughly with water and ether, and dried in vacuo to afford 4,5,6,7-tetrahydro-2-benzimidazolone (Compound 7). The solid is collected by suction filtration washed thoroughly with water and ether dried in vacuo

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

実験手順: Under the conditions of Example 59, 2-bromocyclohexanone is reacted with the methyl ester of N-methylanthranilic acid. After recrystallization from methanol, the methyl ester of 9-methyl-5,6,7,8-tetrahydrocarbazole-1-carboxylic acid is obtained in a 15% yield, m.p. 56° C. After recrystallization from methanol

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

実験手順: Under the conditions of Example 60, 2-bromocyclohexanone is reacted with the methyl ester of 2-amino-5-methylbenzoic acid; after recrystallization from cyclohexane, the methyl ester of 3-methyl-5,6,7,8-tetrahydrocarbazole-1-carboxylic acid is obtained in a 55% yield, m.p. 111° C. after recrystallization from cyclohexane

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

実験手順: Under the conditions of Example 60, 2-bromocyclohexanone is reacted with the methyl ester of 2-amino-5-methylbenzoic acid; after recrystallization from cyclohexane, the methyl ester of 3-methyl-5,6,7,8-tetrahydrocarbazole-1-carboxylic acid is obtained in a 55% yield, m.p. 111° C. after recrystallization from cyclohexane

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

実験手順: 2-Bromocyclohexan-1-one (K. Tanemura, T. Suzuki, Y. Nishida, K. Satsumabayashi, T. Horaguchi, Chem. Commun. 2004, 470-471) (0.55 g, 3.11 mmol) was dissolved in DMSO (3 mL). Sodium azide (1.00 g, 15.5 mmol) was added, and the resulting mixture was stirred for 2 h. The solution was then diluted with water (50 mL) and extracted with diethyl ether (2×20 mL). The organic layers were combined, washed with water (2×20 mL), dried over Na2SO4(s), filtered, and concentrated under reduced pressure. The resulting oil was found to be pure by NMR analysis and was used without further purification (0.40 g, 2.87 mmol, 92% yield). extracted with diethyl ether (2×20 mL) washed with water (2×20 mL) dried over Na2SO4(s) filtered concentrated under reduced pressure was used without further purification (0.40 g, 2.87 mmol, 92% yield)

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a nitrogen atmosphere at −5° C., 260 ml of 2.6M n-butyllithium in hexane was added to a mixture of 58 g of 1,1,1,3,3,3-hexafluoro-2-propanol and 260 g of tetrahydrofuran, followed by one hour of stirring at 5° C. Then 59 g of 2-bromocyclohexanone was added at 5° C. The mixture was stirred for 10 hours, after which dilute hydrochloric acid was added to quench the reaction and neutralize the reaction mixture. Then 310 g of a 10% aqueous solution of sodium hydroxide was added to the reaction mixture, from which an aqueous layer was separated. It was made acidic by adding 150 g of 20% dilute hydrochloric acid and combined with 250 g of toluene, after which separatory operation was performed to separate an organic layer. The organic layer was concentrated and purified by recrystallization from hexane, obtaining 58 g of the product (yield 72%). The mixture was stirred for 10 hours to quench the reaction was separated by adding 150 g of 20% dilute hydrochloric acid to separate an organic layer The organic layer was concentrated purified by recrystallization from hexane

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a nitrogen atmosphere at −5° C., 260 ml of 2.6M n-butyllithium in hexane was added to a mixture of 58 g of 1,1,1,3,3,3-hexafluoro-2-propanol and 260 g of tetrahydrofuran, followed by one hour of stirring at 5° C. Then 59 g of 2-bromocyclohexanone was added at 5° C. The mixture was stirred for 10 hours, after which dilute hydrochloric acid was added to quench the reaction and neutralize the reaction mixture. Then 310 g of a 10% aqueous solution of sodium hydroxide was added to the reaction mixture, from which an aqueous layer was separated. It was made acidic by adding 150 g of 20% dilute hydrochloric acid and combined with 250 g of toluene, after which separatory operation was performed to separate an organic layer. The organic layer was concentrated and purified by recrystallization from hexane, obtaining 58 g of the product (yield 72%). The mixture was stirred for 10 hours to quench the reaction was separated by adding 150 g of 20% dilute hydrochloric acid to separate an organic layer The organic layer was concentrated purified by recrystallization from hexane

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

実験手順: A mixture of 2-[(2,6-di-(1-pyrrolidinyl)pyrimidin-4-yl)amino]ethanol (VI, Example1, 5.55 g), 2-bromocyclohexanone (3.54 g), N,N-diisopropylethylamine (2.65 g) and acetonitrile (60 mL) is heated at reflux for 44 hr. The reaction mixture is cooled to 20°-25° and concentrated under reduced pressure. The residue is partitioned between methylene chloride and aqueous sodium bicarbonate solution. The organic phase is dried over sodium sulfate, filtered, and concentrated. Chromatography (silica gel, 2.5% acetone/chloroform) gives the title compound, NMR (CDCl3) 7.64, 4.05, 3.91, 3.67, 3.55, 2.72, 2.56, 2.0-1.7 δ; MS (m/z) calc'd=355.2372, found=355.2368. is heated at reflux for 44 hr The reaction mixture is cooled to 20°-25° concentrated under reduced pressure The residue is partitioned between methylene chloride and aqueous sodium bicarbonate solution The organic phase is dried over sodium sulfate filtered concentrated

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

実験手順: To a solution of ammonium dithiocarbamate (1.4 g, 12.4 mmol) in 25 mL of ethanol was added 2-bromocyclohexanone (2.2 g, 12.4 mmol). The reaction was stirred at rt overnight. The next morning the reaction was heated at 70° C. for 1 h. The solvent was removed under reduced pressure. The product was subjected to flash chromatography (3:1 hexane/ethyl acetate) to recover a yellow solid. Recrystallization from ethyl acetate afforded 0.54 g of 2-mercapto-4,5,6,7-tetrahydrobenzothiazole. The next morning the reaction was heated at 70° C. for 1 h The solvent was removed under reduced pressure to recover a yellow solid Recrystallization from ethyl acetate

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

実験手順: To a solution of ammonium dithiocarbamate (1.4 g, 12.4 mmol) in 25 mL of ethanol was added 2-bromocyclohexanone (2.2 g, 12.4 mmol). The reaction was stirred at rt overnight. The next morning the reaction was heated at 70° C. for 1 h. The solvent was removed under reduced pressure. The product was subjected to flash chromatography (3:1 hexane/ethyl acetate) to recover a yellow solid. Recrystallization from ethyl acetate afforded 0.54 g of 2-mercapto-4,5,6,7-tetrahydrobenzothiazole. The next morning the reaction was heated at 70° C. for 1 h The solvent was removed under reduced pressure to recover a yellow solid Recrystallization from ethyl acetate

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

実験手順: A mixture of 2-bromocyclohexanone (6.23 g, 0.035 mol) and urea (2.1 g, 0.035 mol) is refluxed in a solution of ammonium acetate (10 g), acetic acid (15 mL) and water (50 mL) for 4 h. Upon cooling slowly to room temp, white crystals form in the reaction vessel. The solid is collected by suction filtration, washed thoroughly with water and ether, and dried in vacuo to afford 4,5,6,7-tetrahydro-2-benzimidazolone (Compound 7). The solid is collected by suction filtration washed thoroughly with water and ether dried in vacuo

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

実験手順: A mixture of 2-bromocyclohexanone (6.23 g, 0.035 mol) and urea (2.1 g, 0.035 mol) is refluxed in a solution of ammonium acetate (10 g), acetic acid (15 mL) and water (50 mL) for 4 h. Upon cooling slowly to room temp, white crystals form in the reaction vessel. The solid is collected by suction filtration, washed thoroughly with water and ether, and dried in vacuo to afford 4,5,6,7-tetrahydro-2-benzimidazolone (Compound 7). The solid is collected by suction filtration washed thoroughly with water and ether dried in vacuo