Methanol → 2-[4-((R)-3-dimethylaminopyrrolidin-1-yl)-3-fluorophenyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid methyl ester

関与物質

役割	名称	HCID	仕込み量
反応物	Methanol	HCID 887	—
反応物	Dimethylformamide	HCID 6228	—
反応物	Triethylamine	HCID 8471	—
反応物	Trifluoromethanesulfonic acid 2-[4-((R)-3-dimethylaminopyrrolidin-1-yl)-3-fluorophenyl]-1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl ester	HCID 86635103	—
触媒	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
生成物	2-[4-((R)-3-dimethylaminopyrrolidin-1-yl)-3-fluorophenyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-6-carboxylic acid methyl ester	HCID 68990613	—

反応条件

温度	50 °C

反応手順

Triethylamine (1.0 g) and then Pd(dppf)Cl2 (365 mg) were added to a mixture of trifluoromethanesulfonic acid 2-[4-((R)-3-dimethylaminopyrrolidin-1-yl)-3-fluorophenyl]-1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl ester (2.5 g), DMF (50 mL) and methanol (25 mL). The mixture was heated at 50° C. in an autoclave under a CO atmosphere (5 bar) for 6 hours. The cooled and decompressed reaction mixture was partitioned between water and ethyl acetate. The organic phase was dried over sodium sulfate and concentrated. The residue was purified by preparative HPLC. The product with the molecular weight of 411.48 (C23H26FN3O3) was obtained in this way; MS (ESI): 412 (M+H+).

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US08822495B2
出典データセット	uspto-grants-2014_09
ORD ID	ord-1781d5c5563a47a398986bd54da62b43
出典メモ	uspto-grants-2014_09