Tetrahydrofuran → N~2~-{2-Chloro-4-[(4-Methylpiperazin-1-Yl)carbonyl]phenyl}-N~2~,N~8~-Dimethyl-4,5-Dihydrothieno[3,2-D][1]benzoxepine-2,8-Dicarboxamide

関与物質

役割	名称	HCID	仕込み量
反応物	Tetrahydrofuran	HCID 8028	—
反応物	1,8-Diazabicyclo(5.4.0)undec-7-ene	HCID 81184	—
反応物	8-bromo-N-(2-chloro-4-(4-methylpiperazine-1-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide	HCID 56834369	—
触媒	Molybdenum carbonyl (Mo(CO)6)	HCID 98885	—
触媒	trans-Bis(acetato)bis[2-[bis(2-methylphenyl)phosphino]benzyl]dipalladium(II)	HCID 11104995	—
溶媒	Methylamine	HCID 6329	—
溶媒	Ethyl Acetate	HCID 8857	—
生成物	N~2~-{2-Chloro-4-[(4-Methylpiperazin-1-Yl)carbonyl]phenyl}-N~2~,N~8~-Dimethyl-4,5-Dihydrothieno[3,2-D][1]benzoxepine-2,8-Dicarboxamide	HCID 44242776	32%

反応条件

温度	150 °C

反応手順

To a solution containing 8-bromo-N-(2-chloro-4-(4-methylpiperazine-1-carbonyl)phenyl)-N-methyl-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamide (0.075 g, 0.13 mmol) in tetrahydrofuran (1.50 mL, 18.5 mmol), 2.00 M of methylamine in tetrahydrofuran (0.196 mL) was added molybdenumhexacarbonyl (34.4 mg, 0.130 mmol), trans-di(mu-acetato)bis[o-(di-o-tolylphosphino)benzyl]dipalladium (II) (18.3 mg, 0.0196 mmol) then 1,8-diazabicyclo[5.4.0]undec-7-ene (9.75 uL, 0.0652 mmol) and capped quickly to prevent CO gas from escaping. The reaction mixture was heated in a microwave at 150° C. for 20 min. The reaction mixture was diluted with EtOAc then filtered thru celite. The combined organics were dried (Na2SO4), filtered and concentrated. The crude was submitted for RP HPLC to give 181 (yield 32%). MS: (ESI+) 553.2

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US08846762B2
出典データセット	uspto-grants-2014_09
ORD ID	ord-8309b2d57e7d4087b4811b7d5ede439e
出典メモ	uspto-grants-2014_09