Methanesulfonic Acid → 6-Ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-5-(3-nitrophenoxy)pyrazine-2-carboxamide

HRID 1526163Notes

Reaction equation

Cl[C:2]1[C:3]([C:20]([NH2:22])=[O:21])=[N:4][C:5]([CH2:18][CH3:19])=[C:6]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=2)[N:7]=1.[CH3:23][N:24]1[CH2:29][CH2:28][N:27]([C:30]2[CH:36]=[CH:35][C:33]([NH2:34])=[CH:32][CH:31]=2)[CH2:26][CH2:25]1.CS(O)(=O)=O.C(=O)([O-])O.[Na+]>CN1CCCC1=O>[CH2:18]([C:5]1[N:4]=[C:3]([C:20]([NH2:22])=[O:21])[C:2]([NH:34][C:33]2[CH:32]=[CH:31][C:30]([N:27]3[CH2:26][CH2:25][N:24]([CH3:23])[CH2:29][CH2:28]3)=[CH:36][CH:35]=2)=[N:7][C:6]=1[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=1)[CH3:19]

Participants

Conditions

Temperature: 200 °C

Procedure

A mixture of 3-chloro-6-ethyl-5-(3-nitrophenoxy)pyrazine-2-carboxamide (500 mg), 4-(4-methylpiperazin-1-yl)aniline (300 mg), methanesulfonic acid (201 μl), and N-methylpyrrolidone (2 mL) was heated in a microwave reaction device at 200° C. for 1 hour. To the reaction mixture was added 4-(4-methylpiperazin-1-yl)aniline (150 mg) and the mixture was heated at 200° C. for 30 minutes. To the reaction mixture was added a saturated aqueous sodium hydrogen carbonate solution, and the precipitated solid was collected by filtration and then dried. The obtained solid was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-200:10:1) to obtain 6-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-5-(3-nitrophenoxy)pyrazine-2-carboxamide (308 mg) as a yellow solid.

Workup

temperaturethe mixture was heated at 200° C. for 30 minutes
filtrationthe precipitated solid was collected by filtration
customdried
customThe obtained solid was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-200:10:1)

Sources & evidence

ORD record: ord-31df3ccca2a7445ba3e7b655e21a7e80
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09085540B2

Reaction notes

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