Hydrochloric Acid → {1-[2-(4'-Chloro-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester

関与物質

役割	名称	HCID	仕込み量
反応物	Hydrochloric Acid	HCID 313	—
反応物	Diisopropylethylamine	HCID 81531	—
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	2-((Methoxycarbonyl)amino)-3-methylbutanoic acid	HCID 13821101	—
反応物	2-(4'-Chloro-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester	HCID 66620530	—
溶媒	Methanol	HCID 887	—
溶媒	Dimethylformamide	HCID 6228	—
溶媒	Ethyl Acetate	HCID 8857	—
生成物	{1-[2-(4'-Chloro-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester	HCID 66621197	96.5%

反応条件

温度	50 °C

反応手順

2-(4′-Chloro-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.66 g, 4.14 mmol) was dissolved in methanol (20 mL) and concentrated HCl (4 mL) was added. The mixture was stirred at 50° C. for 80 min then cooled and concentrated. The residue was treated with 2-methoxycarbonylamino-3-methyl-butyric acid (870 mg, 4.97 mmol) and HATU (2.05 g, 5.38 mmol) and brought up in DMF (20 mL). The mixture was cooled to 0° C. and DIPEA (3.60 mL, 20.7 mmol). After 100 min, the reaction mixture was diluted with ethyl acetate (250 mL) and washed with water and brine. The organic phase was dried over magnesium sulfate and concentrated. The resulting residue was purified by silica column chromatography (50% to 80% EtOAc/hexanes) to afford {1-[2-(4′-Chloro-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (1.83 g, 96% over 2 steps).

情報源と証拠

DOI	10.6084/m9.figshare.5104873.v1
特許番号	US08822430B2
出典データセット	uspto-grants-2014_09
ORD ID	ord-5ab1563ea4074a3ab2eb6843f5a4d3ed
出典メモ	uspto-grants-2014_09