Water → Bms-777607

HRID 408041

反応式

HRID 408041 の反応式
[Cl:1][C:2]1[C:3](C(N)=O)=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]2[C:19](=[O:34])[N:20]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)[CH:21]=[CH:22][C:23]=2OCC)=[O:17])=[CH:11][C:10]=1[F:35].O.[C:40]([OH:43])(=O)[CH3:41].C(O)(=O)C.IC1C=CC=CC=1.CC#[N:57]>CCOC(C)=O>[NH2:57][C:3]1[C:2]([Cl:1])=[C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]3[C:19](=[O:34])[N:20]([C:27]4[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=4)[CH:21]=[CH:22][C:23]=3[O:43][CH2:40][CH3:41])=[O:17])=[CH:11][C:10]=2[F:35])[CH:6]=[CH:5][N:4]=1

参加物

6

反応物 4

HCID 962WaterHCID 6342AcetonitrileHCID 12217721Iodo benzene diacetateHCID 252319783-Chloro-4-(4-(4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamido)-2-fluorophenoxy)picolinamide

生成物 1

HCID 24794418Bms-777607収率 74%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

To a mixture of 3-chloro-4-(4-(4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamido)-2-fluorophenoxy)picolinamide (13.9 g, 25.7 mmol) in EtOAc (200 mL), MeCN (200 mL), and water (100 mL) at 0° C. was added iodobenzene diacetate (9.93 g, 30.8 mmol). The reaction mixture was slowly warmed to room temperature and stirred for 1 h. The resulting precipitate was filtered and washed with ethyl acetate. The combined filtrates were washed with saturated aqueous sodium bicarbonate solution and the organic phase was dried over anhydrous sodium sulfate and concentrated in vacuo. This residue and the original precipitate were combined and purified by flash chromatography (SiO2, 0-2% methanol/chloroform gradient elution) to give N-(4-(2-Amino-3-chloropyridin-4-yloxy )-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (9.8 g, 74%) as an off-white solid. 1H NMR (DMSO-d6) δ 10.57 (s, 1H), 7.83-7.79 (m, 2H), 7.67 (d, 1H, J=5.6 Hz), 7.41-7.38 (m, 3H), 7.36-7.22 (m, 3H), 6.44 (d, 1H, J=7.6 Hz), 6.36 (br s, 2H), 5.86 (d, 1H, J=6.0 Hz), 4.18 (q, 2H, J =7.2 Hz), 1.23 (t, 3H, J=7.2 Hz); MS (ESI+) m/z 513.09 (M+H)+.

後処理

  1. filtrationThe resulting precipitate was filtered
  2. washwashed with ethyl acetate
  3. washThe combined filtrates were washed with saturated aqueous sodium bicarbonate solution
  4. dry with materialthe organic phase was dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. custompurified by flash chromatography (SiO2, 0-2% methanol/chloroform gradient elution)

出典と根拠

ORDレコード
ord-6d4add3394c643faa07068f763f1feb6
出典データセット
uspto-grants-2014_06
特許番号
US08754230B2

関連ノート

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