Potassium Carbonate → 3-Fluoro-4-[(3-{[(1S)-2-hydroxy-1-methylethyl]oxy}-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenyl)oxy]-N,N-dimethylbenzamide

HRID 20530Notes

Reaction equation

C(=O)([O-])[O-].[K+].[K+].[OH:7][C:8]1[CH:9]=[C:10]([CH:20]=[C:21]([O:23][C@@H:24]([CH3:27])[CH2:25][OH:26])[CH:22]=1)[C:11]([NH:13][C:14]1[CH:18]=[CH:17][N:16]([CH3:19])[N:15]=1)=[O:12].[F:28][C:29]1[CH:30]=[C:31]([CH:37]=[CH:38][C:39]=1F)[C:32]([N:34]([CH3:36])[CH3:35])=[O:33]>C(#N)C>[F:28][C:29]1[CH:30]=[C:31]([CH:37]=[CH:38][C:39]=1[O:7][C:8]1[CH:9]=[C:10]([C:11]([NH:13][C:14]2[CH:18]=[CH:17][N:16]([CH3:19])[N:15]=2)=[O:12])[CH:20]=[C:21]([O:23][C@@H:24]([CH3:27])[CH2:25][OH:26])[CH:22]=1)[C:32]([N:34]([CH3:36])[CH3:35])=[O:33]

Participants

Conditions

Temperature: 160 °C

Procedure

Potassium carbonate (276 mg) was added to a solution of 3-hydroxy-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide (291 mg) and 3,4-difluoro-N,N-dimethylbenzamide (204 mg) in acetonitrile (3.5 mL) and the stirred mixture heated at 160° C. in a ‘Smith Creator Microwave’ for 15 h. The mixture was allowed to return to ambient temperature and pressure, the acetonitrile evaporated, and the residue chromatographed on silica, eluting with 0-5% methanol in ethyl acetate, to give the desired compound (63 mg). 1H NMR δ (d6-DMSO): 1.22 (d, 3H), 2.94 (s, 6H), 3.49 (m, 2H), 3.76 (s, 3H), 4.54 (m, 1H), 4.83 (t, 1H), 6.53 (m, 1H), 6.76 (m, 1H), 7.14 (s, 1H), 7.24 (m, 2H), 7.40 (s, 1H), 7.47 (d, 1H), 7.57 (m, 1H), 10.83 (br s, 1H). m/z 457 (M+H)+

Workup

customto return to ambient temperature
custompressure, the acetonitrile evaporated
customthe residue chromatographed on silica
washeluting with 0-5% methanol in ethyl acetate

Sources & evidence

ORD record: ord-5efa07e1659a406b8e519ac35913b755
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07745475B2

Reaction notes

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