(2S)-2-methyl-2,3-dihydro-1H-indole

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

実験手順: In a three-necked flask under argon, 0.35 g of the sodium salt of (−)-[4-(2-hydroxymethylmorpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetic acid (example 31b, step 2b) is placed in 5 ml of pyridine and 5 ml of DMF whitish heterogeneous solution. N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride is added at ambient temperature, 0.18 g of (S)-2-methylindoline (CAS 22160-09-4) is added, and the mixture is stirred at ambient temperature for 72 hours. 25 ml of water are added, extraction is carried out with 3 times approximately 25 ml of dichloromethane, washing is carried out with 25 ml of water, washing is carried out with twice approximately 15 ml of 1M hydrochloric acid solution, washing is carried out with 25 ml of water, washing is carried out with 25 ml of saturated NaCl solution, drying is carried out over MgSO4, filtration is carried out through a VF filter, and the resulting product is concentrated under vacuum. The compound obtained is chromatographed on silica gel (40-63 μm), elution being carried out with a mixture of dichloromethane and ethanol (95/5, v/v). The fractions containing the expected compound are combined and evaporated. The compound obtained is triturated from dichloromethane and diisopropyl ether, filtered, and dried at ambient temperature (20° C.). (+)-6-(2-Hydroxymethylmorpholin-4-yl)-2-[2-((S)-2-methyl-2,3-dihydroindol-1-yl)-2-oxoethyl]-3H-pyrimidin-4-one is isolated (0.11 g). extraction washing washing washing washing drying is carried out over MgSO4, filtration filter the resulting product is concentrated under vacuum The compound obtained is chromatographed on silica gel (40-63 μm), elution being carried out with a mixture of dichloromethane and ethanol (95/5 The fractions containing the expected compound evaporated The compound obtained is triturated from dichloromethane and diisopropyl ether filtered dried at ambient temperature (20° C.)

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a three-necked flask under argon, 0.5 g of the sodium salt of [4-(2-fluoromethylmorpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetic acid previously obtained (example 30b, step 3b) is placed in 7 ml of pyridine and 7 ml of dimethylformamide, and then N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride is added at ambient temperature, followed by 0.25 g of (S)-2-methylindoline (CAS 22160-09-4). The reaction medium is stirred at ambient temperature (20° C.) for 72 hours. 25 ml of water are added, extraction is carried out with 3 times approximately 25 ml of dichloromethane, washing is carried out with 25 ml of water, washing is carried out with twice approximately 15 ml of 1M hydrochloric acid solution, washing is carried out with 25 ml of water, washing is carried out with 25 ml of saturated NaCl solution, drying is carried out over MgSO4, filtration is carried out through a VF filter, and the resulting product is concentrated under vacuum. The compound obtained is chromatographed on silica gel (40-63 μm), elution being carried out with a mixture of dichloromethane and ethanol (95/5, v/v). The fractions containing the expected compound are combined and evaporated. The compound obtained is triturated from 1 ml of dichloromethane and 10 ml of diisopropyl ether, filtered, and dried at ambient temperature (20° C.). (+)-6-(2-Fluoromethylmorpholin-4-yl)-2-[2-((S)-2-methyl-2,3-dihydroindol-1-yl)-2-oxoethyl]-3H-pyrimidin-4-one is isolated (0.315 g). extraction washing washing washing washing drying is carried out over MgSO4, filtration filter the resulting product is concentrated under vacuum The compound obtained is chromatographed on silica gel (40-63 μm), elution being carried out with a mixture of dichloromethane and ethanol (95/5 The fractions containing the expected compound evaporated The compound obtained is triturated from 1 ml of dichloromethane and 10 ml of diisopropyl ether filtered dried at ambient temperature (20° C.)

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a three-necked flask under argon, 0.5 g of the sodium salt of [4-(2-fluoromethylmorpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetic acid previously obtained (example 30b, step 3b) is placed in 7 ml of pyridine and 7 ml of dimethylformamide, and then N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride is added at ambient temperature, followed by 0.25 g of (S)-2-methylindoline (CAS 22160-09-4). The reaction medium is stirred at ambient temperature (20° C.) for 72 hours. 25 ml of water are added, extraction is carried out with 3 times approximately 25 ml of dichloromethane, washing is carried out with 25 ml of water, washing is carried out with twice approximately 15 ml of 1M hydrochloric acid solution, washing is carried out with 25 ml of water, washing is carried out with 25 ml of saturated NaCl solution, drying is carried out over MgSO4, filtration is carried out through a VF filter, and the resulting product is concentrated under vacuum. The compound obtained is chromatographed on silica gel (40-63 μm), elution being carried out with a mixture of dichloromethane and ethanol (95/5, v/v). The fractions containing the expected compound are combined and evaporated. The compound obtained is triturated from 1 ml of dichloromethane and 10 ml of diisopropyl ether, filtered, and dried at ambient temperature (20° C.). (+)-6-(2-Fluoromethylmorpholin-4-yl)-2-[2-((S)-2-methyl-2,3-dihydroindol-1-yl)-2-oxoethyl]-3H-pyrimidin-4-one is isolated (0.315 g). extraction washing washing washing washing drying is carried out over MgSO4, filtration filter the resulting product is concentrated under vacuum The compound obtained is chromatographed on silica gel (40-63 μm), elution being carried out with a mixture of dichloromethane and ethanol (95/5 The fractions containing the expected compound evaporated The compound obtained is triturated from 1 ml of dichloromethane and 10 ml of diisopropyl ether filtered dried at ambient temperature (20° C.)

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

実験手順: The product is prepared by following the procedure described in example 1a (step 5a) using 88 mg of sodium (5-fluoro-1-methyl-4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetate described in step 2a and 40 mg of (S)-2-methyl-2,3-dihydro-1H-indole (which can be prepared according to Krasnov, V. P. et al. (Mendeleev Commun. (2002), 12(1), 27-28). After silica column purification: eluent 98/02 dichloromethane/methanol, 60 mg of 5-fluoro-3-methyl-2-[2-((S)-2-methyl-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one are obtained in the form of a solid, the characteristics of which are the following: The product is prepared can be prepared After silica column purification

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

実験手順: The product is prepared by following the procedure described in example 1a (step 5a) using 88 mg of sodium (5-fluoro-1-methyl-4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetate described in step 2a and 40 mg of (S)-2-methyl-2,3-dihydro-1H-indole (which can be prepared according to Krasnov, V. P. et al. (Mendeleev Commun. (2002), 12(1), 27-28). After silica column purification: eluent 98/02 dichloromethane/methanol, 60 mg of 5-fluoro-3-methyl-2-[2-((S)-2-methyl-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one are obtained in the form of a solid, the characteristics of which are the following: The product is prepared can be prepared After silica column purification