1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → (+)-6-(2-Hydroxymethylmorpholin-4-yl)-2-[2-((S)-2-methyl-2,3-dihydroindol-1-yl)-2-oxoethyl]-3H-pyrimidin-4-one

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Reaction Steps

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).

Provenance & Evidence