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

HRID 1526164Notes

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]([CH:30]2[CH2:35][CH2:34][N:33]([C:36]3[CH:42]=[CH:41][C:39]([NH2:40])=[CH:38][CH:37]=3)[CH2:32][CH2:31]2)[CH2:26][CH2:25]1.FC(F)(F)C(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:40][C:39]2[CH:41]=[CH:42][C:36]([N:33]3[CH2:34][CH2:35][CH:30]([N:27]4[CH2:28][CH2:29][N:24]([CH3:23])[CH2:25][CH2:26]4)[CH2:31][CH2:32]3)=[CH:37][CH:38]=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: 150 °C

Procedure

A mixture of 3-chloro-6-ethyl-5-(3-nitrophenoxy)pyrazine-2-carboxamide (400 mg), 4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]aniline (374 mg), trifluoroacetic acid (209 μL), and N-methylpyrrolidone (2.8 mL) was heated at 150° C. for 16 hours. 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-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)-5-(3-nitrophenoxy)pyrazine-2-carboxamide (383 mg) as a brown solid.

Workup

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-6cf4dc9aa9c141d181838dfb98bf076c
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09085540B2

Reaction notes

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