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 596011ノート

反応式

HRID 596011 の反応式
[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

参加物

8

反応物 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

生成物 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-fluorobenzamide収率 58%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-55f3fedf4c7143c69d924429aeebafb1
出典データセット
uspto-grants-2016_01
特許番号
US09242996B2

反応ノート

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