Water → Bms-777607

HRID 408041

반응식

HRID 408041 반응식
[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

참가 물질

6

반응물 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

생성물 1

HCID 24794418Bms-777607수율 74%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

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)+.

후처리

  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)

출처 및 근거

ORD 기록
ord-6d4add3394c643faa07068f763f1feb6
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08754230B2

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