Cesium carbonate → 4-chloro-2-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta(4,5)pyrrolo(1,2-a)pyrazin-2-yl)nicotinaldehyde

関与物質

役割	名称	HCID	仕込み量
反応物	Cesium carbonate	HCID 10796	—
反応物	1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)	HCID 636044	—
反応物	7,7-dimethyl-3,4,7,8-tetrahydro-2H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1(6H)-one	HCID 58044202	—
反応物	2-Bromo-4-chloropyridine-3-carbaldehyde	HCID 86683914	—
触媒	Bis(dibenzylideneacetone)palladium	HCID 9811564	—
溶媒	1,4-Dioxane	HCID 31275	—
生成物	4-chloro-2-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta(4,5)pyrrolo(1,2-a)pyrazin-2-yl)nicotinaldehyde	HCID 76854078	31.7%

反応条件

温度	90 °C

反応手順

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 2-bromo-4-chloronicotinaldehyde 103a (3.0 g, 13.6 mmol), 4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one 107e (1.84 g, 9.0 mmol), tris(dibenzylideneacetone)dipalladium(0) (826 mg, 0.9 mmol), XantPhos (1.04 mg, 1.8 mmol), Cs2CO3 (5.8 g, 18.0 mmol), and 1,4-dioxane (40 mL). After three cycles of vacuum/argon flush, the mixture was heated at 90° C. for 5 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was recrystallized from ethyl acetate to afford 108a as a yellow solid (730 mg, purity: 99%; yield: 31.7%). MS: [M+H]+ 344.0.

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US09238655B2
出典データセット	uspto-grants-2016_01
ORD ID	ord-a7b06f0e951d436ebcb209f0a156c7df
出典メモ	uspto-grants-2016_01