Diisopropylethylamine → (2S,4R)-2-(3-Chloro-2-fluoro-5-methoxycarbonyl-benzylcarbamoyl)-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester

참여 물질

역할	이름	HCID	투입량
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	(2S,4R)-1-[(tert-butoxy)carbonyl]-4-fluoropyrrolidine-2-carboxylic acid	HCID 12043048	—
반응물	3-Aminomethyl-5-chloro-4-fluoro-benzoic acid methyl ester	HCID 68283927	—
용매	Dimethylformamide	HCID 6228	—
생성물	(2S,4R)-2-(3-Chloro-2-fluoro-5-methoxycarbonyl-benzylcarbamoyl)-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester	HCID 68283553	—

반응 단계

To a mixture of N-boc-trans-4-fluoro-L-proline (143 mg, 0.61 mmol), 3-aminomethyl-5-chloro-4-fluoro-benzoic acid methyl ester (prepared as described in Part C, 275 mg, 0.61 mmol) and HATU (0.35 g, 0.92 mmol) in DMF (4 mL) was added DIPEA (430 μl, 2.45 mmol) and the resulting solution was stirred overnight at ambient temperature. The reaction mixture was splitted in two batches and the crude product was purified without aqueous workup by RP-preparative HPLC (Waters Sunfire, C18-ODB, 5 μm, 30×100 mm, 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 40 ml/min) to give the title compound. MS (LC-MS): 333.0 [M−100]+; tR (HPLC conditions c): 5.05 min.

출처 및 근거

DOI	10.6084/m9.figshare.5104873.v1
특허 번호	US09085555B2
출처 데이터셋	uspto-grants-2015_07
ORD ID	ord-e823080c978c488c895cb85443b76767
출처 메모	uspto-grants-2015_07