1,2-Dichloroethane → (S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(2-azido-1-(3-chloro-5-fluorophenyl)ethyl)-2-fluorobenzamide

HRID 596011노트

반응식

HRID 596011 반응식
[NH2:1][C:2]1[C:3]([C:14]2[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[C:16]([F:23])[CH:15]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:6][N:7]=1.[N:24]([CH2:27][C@H:28]([C:30]1[CH:35]=[C:34]([F:36])[CH:33]=[C:32]([Cl:37])[CH:31]=1)[NH2:29])=[N+:25]=[N-:26].CCN(C(C)C)C(C)C.C(Cl)CCl>CN(C=O)C.CCOC(C)=O.O>[NH2:1][C:2]1[C:3]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([NH:29][C@@H:28]([C:30]3[CH:35]=[C:34]([F:36])[CH:33]=[C:32]([Cl:37])[CH:31]=3)[CH2:27][N:24]=[N+:25]=[N-:26])=[O:19])=[C:16]([F:23])[CH:15]=2)=[N:4][C:5]([CH:8]2[CH2:9][CH2:10][O:11][CH2:12][CH2:13]2)=[CH:6][N:7]=1

참가 물질

8

반응물 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 1180447134-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoic acidHCID 118046055(S)-2-azido-1-(3-chloro-5-fluorophenyl)ethanamine

생성물 1

HCID 118046045(S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(2-azido-1-(3-chloro-5-fluorophenyl)ethyl)-2-fluorobenzamide수율 58%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoic acid (126 mg, 0.398 mmol) in DMF (1328 μl) was added (S)-2-azido-1-(3-chloro-5-fluorophenyl)ethanamine (100.0 mg, 0.398 mmol), DIEA (348 μl, 1.991 mmol), EDC (153 mg, 0.797 mmol), and aza-HOBt (81 mg, 0.597 mmol). The reaction mixture was stirred for 15 h. After water was added, the reaction mixture was worked up with EtOAc. The organic layer was dried over Na2SO4, filtered off, and concentrated in vacuo. The crude product was purified by flash chromatography (gradient EtOAc in heptane) to provide (S)-4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(2-azido-1-(3-chloro-5-fluorophenyl)ethyl)-2-fluorobenzamide (118 mg, 58%). LCMS (m/z): 514.2 (MH+), 0.91 min.

후처리

  1. dry with materialThe organic layer was dried over Na2SO4
  2. filtrationfiltered off
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by flash chromatography (gradient EtOAc in heptane)

출처 및 근거

ORD 기록
ord-55f3fedf4c7143c69d924429aeebafb1
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09242996B2

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