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

HRID 1527319노트

반응식

HRID 1527319 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([C:13]#[N:14])[CH2:10][C@H:9]1[C:15]([OH:17])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:18][C:19]1[C:20]([F:27])=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH2:22][NH2:23].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([C:13]#[N:14])[CH2:10][C@H:9]1[C:15](=[O:17])[NH:23][CH2:22][C:21]1[CH:24]=[CH:25][CH:26]=[C:19]([Cl:18])[C:20]=1[F:27])=[O:7])([CH3:2])([CH3:3])[CH3:4]

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 2773614(3-Chloro-2-fluorophenyl)methanamineHCID 14842641(2S,4S)-1-(tert-butoxycarbonyl)-4-cyanopyrrolidine-2-carboxylic acid

생성물 1

HCID 68283946(2S,4S)-2-(3-Chloro-2-fluoro-benzylcarbamoyl)-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

To a mixture of (2S,4S)-4-cyano-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (700 mg, 2.91 mmol), 3-chloro-2-fluorobenzylamine (558 mg, 3.50 mmol), HBTU (1.66 g, 4.37 mmol) in DMF (15 mL) was added DIPEA (1.5 mL, 8.74 mmol) and the resolution mixture was stirred at RT under nitrogen for 48 h. The mixture was poured in water and extracted with EtOAc (2×). The combined organic extracts were washed with water (1×), dried (Na2SO4), filtered and concentrated. The crude material was purified by flash column chromatography (c-hexane to c-hexane/EtOAc 1:1) to give the desired compound. TLC, Rf (c-hexane/EtOAc 1:1)=0.40; MS: 404.0 [M+Na]+, 380.0 [M−H]−, tR (HPLC conditions a): 3.45 min.

후처리

  1. extractionextracted with EtOAc (2×)
  2. washThe combined organic extracts were washed with water (1×)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by flash column chromatography (c-hexane to c-hexane/EtOAc 1:1)

출처 및 근거

ORD 기록
ord-e6601b86aa814b728a231b9ab0e44bd8
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09085555B2

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