Water → Bms-777607

HRID 1043046Notes

Reaction equation

HRID 1043046 reaction equation
[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

Participants

6

Reactant 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

Product 1

HCID 24794418Bms-777607Yield 74%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

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)+.

Workup

  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)

Sources & evidence

ORD record
ord-5e8c6313814847759c5f6adbe43eb549
Source dataset
uspto-grants-2013_10
Patent number
US08558000B2

Reaction notes

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