Cesium carbonate → 4-(4-(Dimethylcarbamoyl)-3-fluorophenoxy)-N-(1-methyl-1H-pyrazol-3-yl)benzofuran-6-carboxamide

HRID 1643783Notes

Reaction equation

C([O-])([O-])=O.[Cs+].[Cs+].C(O[C:10]([C:12]1[CH:20]=[C:19]([OH:21])[C:15]2[CH:16]=[CH:17][O:18][C:14]=2[CH:13]=1)=[O:11])C.[F:22][C:23]1[CH:33]=[C:32](F)[CH:31]=[CH:30][C:24]=1[C:25]([N:27]([CH3:29])[CH3:28])=[O:26].[CH3:35][N:36]1[CH:40]=[CH:39][C:38]([NH2:41])=[N:37]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH3:28][N:27]([CH3:29])[C:25]([C:24]1[CH:30]=[CH:31][C:32]([O:21][C:19]2[C:15]3[CH:16]=[CH:17][O:18][C:14]=3[CH:13]=[C:12]([C:10]([NH:41][C:38]3[CH:39]=[CH:40][N:36]([CH3:35])[N:37]=3)=[O:11])[CH:20]=2)=[CH:33][C:23]=1[F:22])=[O:26]

Participants

Conditions

Temperature: 150 °C

Procedure

Cs2CO3 (0.806 g, 2.47 mmol) was added to a solution of ethyl 4-hydroxy-benzofuran-6-carboxylate (8a) (0.256 g, 1.24 mmol) and 2,4-difluoro-N,N-dimethylbenzamide (0.287 g, 1.55 mmol) in DMF (5 mL). The mixture was stirred at 150° C. for 8 hours and then cooled to room temperature. 1-Methyl-1H-pyrazol-3-amine (0.21 g, 2.11 mmol) and then HATU (0.71 g, 1.87 mmol) were added. The reaction mixture was stirred at 50° C. for one hour and then filtered. Purification by HPLC gave a solid (200 mg, 39% yield) as the expected product. 1H NMR (400 MHz, DMSO-d6) δ 10.95 (s, 1 H) 8.22 (s, 1 H) 8.16 (m, 1 H)) 7.62-7.36 (s, 1 H) 7.60-7.61 (m, 1 H) 7.39-7.43 (m, 1 H) 7.08-7.11 (m, 1 H) 6.95-6.97 (m, 1 H) 6.89 (s, 1 H) 6.59-6.60 (m, 1 H) 3.78 (s, 3 H) 2.99 (s, 3 H) 2.88 (m, 3 H). LCMS for C22H19FN4O4 m/z 423.10 (M+H)+.

Workup

temperaturecooled to room temperature
stirringThe reaction mixture was stirred at 50° C. for one hour
filtrationfiltered
customPurification by HPLC

Sources & evidence

ORD record: ord-e468cd9a5002472b9179fa729b9162f5
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08119624B2

Reaction notes

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