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

HRID 1527361노트

반응식

HRID 1527361 반응식
[C:1]([N:8]1[CH2:15][C@H:14]([F:16])[CH2:13][C@H:9]1[C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:17][O:18][C:19](=[O:30])[C:20]1[CH:25]=[C:24]([Cl:26])[C:23]([F:27])=[C:22]([CH2:28][NH2:29])[CH:21]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:4]([O:3][C:1]([N:8]1[CH2:15][C@H:14]([F:16])[CH2:13][C@H:9]1[C:10](=[O:12])[NH:29][CH2:28][C:22]1[CH:21]=[C:20]([C:19]([O:18][CH3:17])=[O:30])[CH:25]=[C:24]([Cl:26])[C:23]=1[F:27])=[O:2])([CH3:5])([CH3:6])[CH3:7]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12043048(2S,4R)-1-[(tert-butoxy)carbonyl]-4-fluoropyrrolidine-2-carboxylic acidHCID 682839273-Aminomethyl-5-chloro-4-fluoro-benzoic acid methyl ester

생성물 1

HCID 68283553(2S,4R)-2-(3-Chloro-2-fluoro-5-methoxycarbonyl-benzylcarbamoyl)-4-fluoro-pyrrolidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  1. customThe reaction mixture was splitted in two batches
  2. customthe 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)

출처 및 근거

ORD 기록
ord-e823080c978c488c895cb85443b76767
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09085555B2

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