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Trifluoroacetic acid → 3-{[4-(4-Methylpiperazin-1-yl)phenyl]amino}-5-(3-nitrophenoxy)-6-(prop-1-en-2-yl)pyrazine-2-carboxamide

HRID 1526174
Notes
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Reaction equation

HRID 1526174 reaction equation
Cl[C:2]1[C:3]([C:22]([NH2:24])=[O:23])=[N:4][C:5]([C:18](O)([CH3:20])[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.[CH3:25][N:26]1[CH2:31][CH2:30][N:29]([C:32]2[CH:38]=[CH:37][C:35]([NH2:36])=[CH:34][CH:33]=2)[CH2:28][CH2:27]1.FC(F)(F)C(O)=O.CN1CCCC1=O>O>[CH3:25][N:26]1[CH2:27][CH2:28][N:29]([C:32]2[CH:38]=[CH:37][C:35]([NH:36][C:2]3[C:3]([C:22]([NH2:24])=[O:23])=[N:4][C:5]([C:18]([CH3:20])=[CH2:19])=[C:6]([O:8][C:9]4[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=4)[N:7]=3)=[CH:34][CH:33]=2)[CH2:30][CH2:31]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 13387N-methyl-2-pyrrolidoneHCID 7372534-(4-Methylpiperazin-1-yl)anilineHCID 1176669023-Chloro-6-(2-hydroxypropan-2-yl)-5-(3-nitrophenoxy)pyrazine-2-carboxamide

Product 1

HCID 1176672673-{[4-(4-Methylpiperazin-1-yl)phenyl]amino}-5-(3-nitrophenoxy)-6-(prop-1-en-2-yl)pyrazine-2-carboxamide
Yield 56%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 3-chloro-6-(2-hydroxypropan-2-yl)-5-(3-nitrophenoxy)pyrazine-2-carboxamide (1.48 g), 4-(4-methylpiperazin-1-yl)aniline (883 mg), trifluoroacetic acid (385 μL), and N-methylpyrrolidone (14.8 mL) was heated to 160° C. for 5 hours. To the reaction mixture were added water and 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=1:0:0-30:1:0.1) and washed with ethyl acetate to obtain 3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}-5-(3-nitrophenoxy)-6-(prop-1-en-2-yl)pyrazine-2-carboxamide (1.15 g) as an orange solid.

Workup

  1. filtrationa saturated aqueous sodium hydrogen carbonate solution, and the precipitated solid was collected by filtration
  2. customdried
  3. customThe obtained solid was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-30:1:0.1)
  4. washwashed with ethyl acetate

Sources & evidence

ORD record
ord-0fcfb17e470d4b1c802ef4718dfb8600
Source dataset
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09085540B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes