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

https://huagongshe.com/ko/reaction/79801

참여 물질

역할	이름	HCID	투입량
반응물	Hydrochloric Acid	HCID 313	—
반응물	Diisopropylethylamine	HCID 81531	—
반응물	Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)	HCID 9886157	—
반응물	2-((Methoxycarbonyl)amino)-3-methylbutanoic acid	HCID 13821101	—
반응물	2-(4'-Chloro-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester	HCID 66620530	—
용매	Methanol	HCID 887	—
용매	Dimethylformamide	HCID 6228	—
용매	Ethyl Acetate	HCID 8857	—
생성물	{1-[2-(4'-Chloro-biphenyl-3-ylcarbamoyl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester	HCID 66621197	96.5%

반응 조건

온도	50 °C

반응 단계

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).

출처 및 근거

DOI	10.6084/m9.figshare.5104873.v1
특허 번호	US08841278B2
출처 데이터셋	uspto-grants-2014_09
ORD ID	ord-0ea17b0d604d483e988ce873a5e64265
출처 메모	uspto-grants-2014_09