3-sulfanylpropan-1-ol

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:

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 suspension of sodium hydride (0.068 g) in dry tetrahydrofuran (25 ml) was added dropwise a solution of 3-mercaptopropanol (0.14 g) in dry tetrahydrofuran (5 ml). After 15 minutes, a solution of 5-bromo-3-methyl-1-(2-methylpropyl)-6-[(pyridin-3-yl)carbonyl]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (0.60 g, Example 39 step c) in dry tetrahydrofuran (20 ml) was added dropwise and the reaction was stirred for 3 hours at room temperature. The solution was poured into water and extracted with ethyl acetate. The combined extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal-phase HPLC eluting with a gradient of 0-5% ethanol in dichloromethane to give the title compound as a cream solid (0.35 g). extracted with ethyl acetate The combined extracts were dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure The residue was purified by normal-phase HPLC eluting with a gradient of 0-5% ethanol in dichloromethane

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

実験手順: 22.4 g of 1-(4-chloro-phenyl)-2-(3-hydroxymethyl-piperidin-1-yl)-2-methyl-propan-1-one, 8.39 g of 3-mercaptopropanol and 21.0 g of potassium carbonate are mixed in 75 ml of dried dimethylacetamide. After stirring for 18 h at 80° C., the mixture is filtered to remove solids and poured into ice-water. The crude product is extracted with ethyl acetate, washed with saturated NaCl solution and dried over MgSO4. After ethyl acetate is distilled off, the residue is purified by means of column chromatography on silica gel with ethyl acetate-hexane (40:60) as an eluent, and an oily product is obtained. The structure is confirmed by the 1H-NMR spectrum (CDCl3): δ [ppm] 1.02 (m, 1H), 1.29 (s, 3H), 1.30 (s, 3H), 1.52-1.77 (m, 6H), 1.95 (m, 2H), 2.05 (t, 1H), 2.27 (t, 1H), 2.67 (d, 1H), 2.86 (d, 1H), 3.12 (t, 2H), 3.44 (m, 2H), 3.78 (m, 2H), 7.28 (d, 2H), 8.48 (d, 2H). the mixture is filtered to remove solids poured into ice-water The crude product is extracted with ethyl acetate washed with saturated NaCl solution dried over MgSO4 After ethyl acetate is distilled off the residue is purified by means of column chromatography on silica gel with ethyl acetate-hexane (40:60) as an eluent an oily product is obtained

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

実験手順: 6 g (60%) NaH are added in portions to 50 ml of dry N-methylpyrrolidone (NMP), the mixture is stirred for 15 min, 9.5 g (0.11 mol) of 3-hydroxypropylmercaptan are metered in in the course of 20 min and the mixture is stirred again for 30 min until the evolution of gas has ended. A solution of 14.4 g (0.1 mol) of 4-chloro-2,3-dimethylpyridine-N-oxide in 100 ml of NMP is then added dropwise in the course of 20 min, and the reaction mixture is stirred for 1 h at room tempera- ture, then for 1 h at 70° C. and after this additionally for 1 h at 100° C. are metered in in the course of 20 min the mixture is stirred again for 30 min until the evolution of gas the reaction mixture is stirred for 1 h at room tempera- ture for 1 h at 70° C. additionally for 1 h at 100° C.

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

実験手順: A solution of 2.47 g (10.8 mmol) of 5-Bromo-2,4-dichloropyrimidine in 30 ml of acetonitrile at −20° C. is mixed with 1.5 ml (10.8 mmol) of triethylamine and 1.00 g (10.8 mmol) of 3-Mercapto-propan-1-ol. The batch is slowly warmed to room temperature and stirred for 16 hours. The batch is filtrated to remove the solid precipitate. The filtrate is concentrated by evaporation. 2-Methoxy-2-methyl-propane is added to the remaining residue and the batch is stirred for 15 minutes. The batch is filtrated and the solid precipitate is dried. 3.03 g (10.6 mmol, corresponding to 98% of theory) of the product is obtained. The batch is filtrated to remove the solid precipitate The filtrate is concentrated by evaporation 2-Methoxy-2-methyl-propane is added to the remaining residue the batch is stirred for 15 minutes The batch is filtrated the solid precipitate is dried 3.03 g (10.6 mmol, corresponding to 98% of theory) of the product is obtained

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

実験手順: A solution of 2.47 g (10.8 mmol) of 5-Bromo-2,4-dichloropyrimidine in 30 ml of acetonitrile at −20° C. is mixed with 1.5 ml (10.8 mmol) of triethylamine and 1.00 g (10.8 mmol) of 3-Mercapto-propan-1-ol. The batch is slowly warmed to room temperature and stirred for 16 hours. The batch is filtrated to remove the solid precipitate. The filtrate is concentrated by evaporation. 2-Methoxy-2-methyl-propane is added to the remaining residue and the batch is stirred for 15 minutes. The batch is filtrated and the solid precipitate is dried. 3.03 g (10.6 mmol, corresponding to 98% of theory) of the product is obtained. The batch is filtrated to remove the solid precipitate The filtrate is concentrated by evaporation 2-Methoxy-2-methyl-propane is added to the remaining residue the batch is stirred for 15 minutes The batch is filtrated the solid precipitate is dried 3.03 g (10.6 mmol, corresponding to 98% of theory) of the product is obtained