Water → METHYL (2S,4R)-1-{2-[4-(4-CHLORO-PHENYL)-PIPERAZIN-1-YL]-5-OXO-6,7-DIHYDRO-5H-5lambda4-THIENO [3,2-D]PYRIMIDIN-4-YL}-4-HYDROXY-PYRROLIDINE-2-CARBOXYLATE

https://huagongshe.com/ja/reaction/70098

関与物質

役割	名称	HCID	仕込み量
反応物	Water	HCID 962	—
反応物	Diisopropylethylamine	HCID 81531	—
反応物	(4R)-4-Hydroxy-L-proline methyl ester	HCID 7015125	—
反応物	4-Chloro-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-6,7-dihydro-thieno[3,2-d]pyrimidine 5-oxide	HCID 59475895	—
溶媒	Dichloromethane	HCID 6344	—
溶媒	1,4-Dioxane	HCID 31275	—
生成物	METHYL (2S,4R)-1-{2-[4-(4-CHLORO-PHENYL)-PIPERAZIN-1-YL]-5-OXO-6,7-DIHYDRO-5H-5lambda4-THIENO [3,2-D]PYRIMIDIN-4-YL}-4-HYDROXY-PYRROLIDINE-2-CARBOXYLATE	HCID 59708424	—

反応条件

温度	120 °C

反応手順

500 mg 4-chloro-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-6,7-dihydro-thieno[3,2-d]pyrimidine 5-oxide (cf Example 124), 284.19 mg methyl (2S,4R)-4-hydroxy-pyrrolidine-2-carboxylate and 691.65 μl diisopropylethylamine are placed in 8 ml dioxane, heated to 120° C. in the microwave for 0.3 hours. Then the reaction mixture is combined with water and dichloromethane and extracted. The organic phase is separated off using a phase separation cartridge and evaporated to dryness. The diastereomers are separated by preparative HPLC (method B). 200 mg of Diastereomer I (Example 125) and 160 mg of a Diastereomer 2 (Example 126) are obtained as powders. Analytical HPLC-MS (method A): Diastereomer 1, RT=2.51 min, Diastereomer 2, RT=2.57 min.

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US08822474B2
出典データセット	uspto-grants-2014_09
ORD ID	ord-0985aff65b9b4c70a322c66845821bed
出典メモ	uspto-grants-2014_09