1-Hydroxybenzotriazole → 1-Butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl)-4-[methyl(methylsulfonyl)amino]-1H-indole-6-carboxamide

関与物質

役割	名称	HCID	仕込み量
反応物	1-Hydroxybenzotriazole	HCID 75771	—
反応物	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
反応物	1-Butyl-4-[methyl(methylsulfonyl)amino]-1H-indole-6-carboxylic acid	HCID 21085174	—
反応物	(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol	HCID 57487282	—
溶媒	Dichloromethane	HCID 6344	—
溶媒	Triethylamine	HCID 8471	—
生成物	1-Butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl)-4-[methyl(methylsulfonyl)amino]-1H-indole-6-carboxamide	HCID 57508185	53.2%

反応条件

温度	40 °C

反応手順

To a mixture of 1-Butyl-4-[methyl(methylsulfonyl)amino]-1H-indole-6-carboxylic acid (0.2 g) in methylene chloride (15 mL) was added triethylamine (0.156 g), HOBT (0.105 g), and HATU (0.293 g). The mixture was stirred at 39° C. for 10 minutes at which time (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (0.293 g) was added. The mixture was stirred at 40° C. for 4 h then poured into methylene chloride (50 mL), washed with water followed by brine then dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Column chromatography on silica gel (100 mL) using 5% methanol in methylene chloride as eluent to give 0.21 g of the title compound: MS (ESI+) for C34H42F2N4O4S1 m/z 640.8 (M+H).

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US07727997B2
出典データセット	uspto-grants-2010_06
ORD ID	ord-34564fa2bde2476ea7d73a1bc60a19c3
出典メモ	uspto-grants-2010_06