Dimethylacetamide → 5-(3-Cyano-5-nitrophenoxy)-6-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide

HRID 1526239Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:31]=[C:32]([N+:34]([O-:36])=[O:35])[CH:33]=1)[O:5][C:6]1[N:7]=[C:8]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([N:24]3[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]3)=[CH:20][CH:19]=2)[C:9]([C:14]([NH2:16])=[O:15])=[N:10][C:11]=1[CH2:12][CH3:13].C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C.[CH3:58][N:59](C)C(=O)C>[Zn].[C-]#N.[Zn+2].[C-]#N.FC(F)(F)C([O-])=O.[Pd+2].FC(F)(F)C([O-])=O.O>[C:58]([C:2]1[CH:3]=[C:4]([CH:31]=[C:32]([N+:34]([O-:36])=[O:35])[CH:33]=1)[O:5][C:6]1[N:7]=[C:8]([NH:17][C:18]2[CH:19]=[CH:20][C:21]([N:24]3[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]3)=[CH:22][CH:23]=2)[C:9]([C:14]([NH2:16])=[O:15])=[N:10][C:11]=1[CH2:12][CH3:13])#[N:59]

Participants

Conditions

Temperature: 100 °C

Procedure

Under an argon atmosphere, to a mixture of 5-(3-bromo-5-nitrophenoxy)-6-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (312 mg), zinc powder (19 mg), biphenyl-2-yl (di-tert-butyl)phosphine (40 mg), zinc (II) cyanide (66 mg), and N,N-dimethylacetamide (6.13 mL) was added palladium trifluoroacetate (II) (20 mg), followed by heating at 100° C. for 4 hours. After leaving to be cooled, to the reactant was added water, followed by extraction with ethyl acetate. The organic phase was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol=1:0-9:1) to obtain 5-(3-cyano-5-nitrophenoxy)-6-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (250 mg) as a red solid.

Workup

customAfter leaving
temperatureto be cooled, to the reactant
extractionfollowed by extraction with ethyl acetate
washThe organic phase was washed with saturated brine
dry with materialdried over anhydrous magnesium sulfate
customthe solvent was evaporated under reduced pressure
customThe obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol=1:0-9:1)

Sources & evidence

ORD record: ord-fcbbf95e2490491c958012854163b072
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09085540B2

Reaction notes

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