2-sulfanylacetamide

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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: To a solution containing 5.25g (0.025 mole) of (2,4-dichlorophenoxy)acetaldehyde and 5.0g (0.055 mole) of thioglycolamide in 100 ml of anhydrous ether was added 14.2g (0.10 mole) of boron trifluoride etherate. The resulting solution was stirred at ambient temperature for 6 hours, washed with water, dried (MgSO4), and concentrated to dryness. The residual solid was purified by silica chromatography to give 1.4g of 2-(2,4-dichlorophenoxymethyl)-4-thiazolidinone as a white crystalline solid melting at 134°-136°. washed with water dried (MgSO4) concentrated to dryness The residual solid was purified by silica chromatography

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

実験手順: To a solution containing 5.25 g (0.025 mole) of (2,4-dichlorophenoxy)acetaldehyde and 5.0 g (0.055 mole) of thioglycolamide in 100 ml of anhydrous ether was added 14.2 g (0.10 mole) of boron trifluoride etherate. The resulting solution was stirred at ambient temperature for 6 hours, washed with water, dried (MgSO4), and concentrated to dryness. The residual solid was purified by silica chromatography to give 1.4 g of 2-(2,4-dichlorophenoxymethyl)-4-thiazolidinone as a white crystalline solid melting at 134°-136°. washed with water dried (MgSO4) concentrated to dryness The residual solid was purified by silica chromatography

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: Triethylamine (4.55 g) is added to a solution of 2-mercaptoacetamide (8.00 g, Reference compound No. 40-1) in ethanol (70 ml), then phenacyl bromide (17.5 g) is added to the mixture, and the whole is stirred for four hours. The reaction mixture is concentrated under reduced pressure, water and 0.1 N hydrochloric acid are added to the resulting residue, and the whole is extracted with ethyl acetate. The extract is washed with saturated brine and dried over anhydrous magnesium sulfate. The extract is concentrated under reduced pressure. The resulting residue is suspended in ethanol (200 ml), p-toluenesulfonic acid monohydrate (catalytic amount) is added to the suspension, and the mixture is refluxed for five days. The reaction mixture is cooled to room temperature to precipitate crystals. The crystals are filtered off and washed with ethanol to give the titled reference compound (11.6 g). The reaction mixture is concentrated under reduced pressure, water and 0.1 N hydrochloric acid are added to the resulting residue the whole is extracted with ethyl acetate The extract is washed with saturated brine dried over anhydrous magnesium sulfate The extract is concentrated under reduced pressure p-toluenesulfonic acid monohydrate (catalytic amount) is added to the suspension the mixture is refluxed for five days to precipitate crystals The crystals are filtered off washed with ethanol

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

実験手順: Triethylamine (4.55 g) is added to a solution of 2-mercaptoacetamide (8.00 g, Reference compound No. 40-1) in ethanol (70 ml), then phenacyl bromide (17.5 g) is added to the mixture, and the whole is stirred for four hours. The reaction mixture is concentrated under reduced pressure, water and 0.1 N hydrochloric acid are added to the resulting residue, and the whole is extracted with ethyl acetate. The extract is washed with saturated brine and dried over anhydrous magnesium sulfate. The extract is concentrated under reduced pressure. The resulting residue is suspended in ethanol (200 ml), p-toluenesulfonic acid monohydrate (catalytic amount) is added to the suspension, and the mixture is refluxed for five days. The reaction mixture is cooled to room temperature to precipitate crystals. The crystals are filtered off and washed with ethanol to give the titled reference compound (11.6 g). The reaction mixture is concentrated under reduced pressure, water and 0.1 N hydrochloric acid are added to the resulting residue the whole is extracted with ethyl acetate The extract is washed with saturated brine dried over anhydrous magnesium sulfate The extract is concentrated under reduced pressure p-toluenesulfonic acid monohydrate (catalytic amount) is added to the suspension the mixture is refluxed for five days to precipitate crystals The crystals are filtered off washed with ethanol

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of (6′-chloro-5′-cyano-4′-difluoromethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-methyl-carbamic acid tert-butyl ester (1.1 g, 2.74 mmol) potassium carbonate (1.9 g, 13.7 mmol) in DMF (15 mL) was treated with 2-mercaptoacetamide (solution of 1 g, 11 mmol in 10 mL of methanol), and the reaction mixture was heated in a sealed tube at 80° C. overnight. The reaction mixture was then cooled to room temperature and filtered. The filtrate was treated with water (50 mL) and the resulting precipitate was collected by filtration to provide 1.03 g (82.4%) of [1-(3-amino-2-carbamoyl-4-difluoromethyl-thieno[2,3-b]pyridin-6-yl)-piperidin-4-yl]-methyl-carbamic acid tert-butyl ester as a tan solid. The reaction mixture was then cooled to room temperature filtered The filtrate was treated with water (50 mL) the resulting precipitate was collected by filtration

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of (6′-chloro-5′-cyano-4′-difluoromethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-methyl-carbamic acid tert-butyl ester (1.1 g, 2.74 mmol) potassium carbonate (1.9 g, 13.7 mmol) in DMF (15 mL) was treated with 2-mercaptoacetamide (solution of 1 g, 11 mmol in 10 mL of methanol), and the reaction mixture was heated in a sealed tube at 80° C. overnight. The reaction mixture was then cooled to room temperature and filtered. The filtrate was treated with water (50 mL) and the resulting precipitate was collected by filtration to provide 1.03 g (82.4%) of [1-(3-amino-2-carbamoyl-4-difluoromethyl-thieno[2,3-b]pyridin-6-yl)-piperidin-4-yl]-methyl-carbamic acid tert-butyl ester as a tan solid. The reaction mixture was then cooled to room temperature filtered The filtrate was treated with water (50 mL) the resulting precipitate was collected by filtration

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

実験手順: 2-Mercaptoacetamide (10.0 g) and methyl 2-chloroacrylate (13.24 g) were dissolved in warm acetone (100 ml), and potassium carbonate (7.58 g) was added in one portion. Heat was evolved. The mixture was heated to reflux for 2 hours. The red solution was filtered hot using a filter aid, and the residue washed with hot acetone (×2). The filtrate and washings were combined and evaporated to obtain the title compound as a red oil (19.92 g) 1H n.m.r. δ (CDCl3 /DMSO-d6) 3.05-3.18 (4H, overlapping s and d, CH2COR and CH2CH) 3.76 (3H,s,CO2Me), 4.67 (1H,t, J=7Hz, CHCH2), 6.92 (1H, br s, CONH), 7.43 (1H, br s, CONH). Heat The mixture was heated to reflux for 2 hours The red solution was filtered hot the residue washed with hot acetone (×2) evaporated