Potassium Cyanide → 4-(4-(2-Carbamoylpyridin-4-yloxy)-3-fluorophenylamino)-2-cyano-N-(2,4-difluorophenyl)pyrimidine-5-carboxamide

HRID 1986107Notes

Reaction equation

[C:1]([C:4]1[CH:9]=[C:8]([O:10][C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]3[C:23]([C:24]([NH:26][C:27]4[CH:32]=[CH:31][C:30]([F:33])=[CH:29][C:28]=4[F:34])=[O:25])=[CH:22][N:21]=[C:20](S(C)(=O)=O)[N:19]=3)=[CH:13][C:12]=2[F:39])[CH:7]=[CH:6][N:5]=1)(=[O:3])[NH2:2].[C-:40]#[N:41].[K+]>CN(C=O)C>[C:1]([C:4]1[CH:9]=[C:8]([O:10][C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]3[C:23]([C:24]([NH:26][C:27]4[CH:32]=[CH:31][C:30]([F:33])=[CH:29][C:28]=4[F:34])=[O:25])=[CH:22][N:21]=[C:20]([C:40]#[N:41])[N:19]=3)=[CH:13][C:12]=2[F:39])[CH:7]=[CH:6][N:5]=1)(=[O:3])[NH2:2]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 4-(4-(2-carbamoylpyridin-4-yloxy)-3-fluorophenylamino)-N-(2,4-difluorophenyl)-2-(methylsulfonyl)pyrimidine-5-carboxamide (200 mg, 0.36 mmol) in DMF (4 mL) was added potassium cyanide (94 mg, 1.44 mmol) and the mixture was heated to 80° C. After 5 h. The mixture was cooled to rt and the solvent was removed in vacuo. The residue was diluted with brine and extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo to give the nitrile (171 mg, 94%) as a solid. MS(ESI+) m/z 506 (M+H)+.

Workup

temperatureThe mixture was cooled to rt
customthe solvent was removed in vacuo
additionThe residue was diluted with brine
extractionextracted with EtOAc
washThe combined organic layers were washed with brine
dry with materialdried over anhydrous MgSO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-6d4bce38c9a24ca5a0f167b0420d5404
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07547782B2

Reaction notes

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