Potassium Carbonate → 5-(3-Amino-2-fluorophenoxy)-6-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide

HRID 1526173Notes

Reaction equation

[NH2:1][C:2]1[C:3]([F:9])=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.Cl[C:11]1[N:12]=[C:13]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]3)=[CH:25][CH:24]=2)[C:14]([C:19]([NH2:21])=[O:20])=[N:15][C:16]=1[CH2:17][CH3:18].C(=O)([O-])[O-].[K+].[K+].CN1CCCC1=O>O>[NH2:1][C:2]1[C:3]([F:9])=[C:4]([CH:5]=[CH:6][CH:7]=1)[O:8][C:11]1[N:12]=[C:13]([NH:22][C:23]2[CH:24]=[CH:25][C:26]([N:29]3[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]3)=[CH:27][CH:28]=2)[C:14]([C:19]([NH2:21])=[O:20])=[N:15][C:16]=1[CH2:17][CH3:18]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 3-amino-2-fluorophenol (50 mg), 5-chloro-6-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (162 mg), potassium carbonate (65 mg), and N-methylpyrrolidone (1 mL) was stirred at 100° C. for 2 hours. To the reaction mixture was added water-saturated brine (1:1), followed by extraction with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; chloroform:methanol=1:0-9:1) to obtain 5-(3-amino-2-fluorophenoxy)-6-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (126 mg) as a yellow solid.

Workup

extractionfollowed by extraction with ethyl acetate
dry with materialThe organic phase was dried over anhydrous sodium sulfate
customthe solvent was evaporated under reduced pressure
customThe residue was purified by silica gel column chromatography (eluent; chloroform:methanol=1:0-9:1)

Sources & evidence

ORD record: ord-e720b5555b944d75a77999c0704ec0ed
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09085540B2

Reaction notes

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