Cesium carbonate → 3-(5-Fluoro-pyridin-3-ylamino)-pyrazine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide

HRID 550575Notes

Reaction equation

Cl.[CH3:2][N:3]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[C:16]([NH2:17])=[N:15][CH:14]=[CH:13][N:12]=2)=[O:10])=[N:4]1.[F:18][C:19]1[CH:20]=[N:21][CH:22]=[C:23](F)[CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH3:2][N:3]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[C:16]([NH:17][C:23]3[CH:22]=[N:21][CH:20]=[C:19]([F:18])[CH:24]=3)=[N:15][CH:14]=[CH:13][N:12]=2)=[O:10])=[N:4]1

Participants

Conditions

Temperature: 180 °C

Procedure

3-Amino-pyrazine-2-carboxylic acid (1-methyl-1H-pyrazol-3-yl)-amide hydrochloride (120 mg, 0.47 mmol), 3,5-difluoropyridine (500 mg, 4.4 mmol), cesium carbonate (610 mg, 1.89 mmol) and 1 mL N,N-dimethylformamide were mixed and stirred under microwave irradiation for 60 minutes at 180° C. The reaction mixture was extracted with sat. NaHCO3— solution and three times ethyl acetate. The combined organic extracts were dried with sodium sulfate, filtered and evaporated. The crude product was purified by flash chromatography on silica gel (heptane/ethyl acetate 90:10->30:70 gradient). The desired compound was obtained as a yellow solid (24 mg, 16%), MS: m/e=314.0 (M+H+).

Workup

extractionThe reaction mixture was extracted with sat. NaHCO3— solution and three times ethyl acetate
dry with materialThe combined organic extracts were dried with sodium sulfate
filtrationfiltered
customevaporated
customThe crude product was purified by flash chromatography on silica gel (heptane/ethyl acetate 90:10->30:70 gradient)

Sources & evidence

ORD record: ord-95cae841b9ad4cc88f669c7296a429bc
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07947685B2

Reaction notes

Loading…