Oxalyl chloride → 5-(3-{[(2E)-4-chlorobuta-2-enoyl]amino}phenoxy)-6-isopropyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide

HRID 1526262Notes

Reaction equation

HRID 1526262 reaction equation
Br[CH2:2]/[CH:3]=[CH:4]/[C:5]([OH:7])=O.C(Cl)(=O)C([Cl:11])=O.[NH2:14][C:15]1[CH:16]=[C:17]([CH:45]=[CH:46][CH:47]=1)[O:18][C:19]1[N:20]=[C:21]([NH:31][C:32]2[CH:37]=[CH:36][C:35]([N:38]3[CH2:43][CH2:42][N:41]([CH3:44])[CH2:40][CH2:39]3)=[CH:34][CH:33]=2)[C:22]([C:28]([NH2:30])=[O:29])=[N:23][C:24]=1[CH:25]([CH3:27])[CH3:26].C(=O)([O-])O.[Na+]>CN1CCCC1=O.CN(C)C=O.C(#N)C>[Cl:11][CH2:2]/[CH:3]=[CH:4]/[C:5]([NH:14][C:15]1[CH:16]=[C:17]([CH:45]=[CH:46][CH:47]=1)[O:18][C:19]1[N:20]=[C:21]([NH:31][C:32]2[CH:33]=[CH:34][C:35]([N:38]3[CH2:39][CH2:40][N:41]([CH3:44])[CH2:42][CH2:43]3)=[CH:36][CH:37]=2)[C:22]([C:28]([NH2:30])=[O:29])=[N:23][C:24]=1[CH:25]([CH3:26])[CH3:27])=[O:7]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 64364114-Bromocrotonic acidHCID 1176670485-(3-Aminophenoxy)-6-isopropyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide

Product 1

HCID 1176675045-(3-{[(2E)-4-chlorobuta-2-enoyl]amino}phenoxy)-6-isopropyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a mixture of 4-bromocrotonic acid (632 mg) and acetonitrile (11 mL) were added oxalyl dichloride (308 μL) and N,N-dimethylformamide (2 droplets) under ice-cooling, followed by stirring at room temperature for 2 hours. To a mixture of 5-(3-aminophenoxy)-6-isopropyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (1.1 g) and N-methylpyrrolidone (22 mL) was added a solution of the acid chloride prepared above under ice-cooling, followed by stirring at room temperature overnight. To the reaction mixture was added a saturated aqueous sodium hydrogen carbonate solution, and the precipitated solid was collected by filtration and dried under reduced pressure. The obtained solid was purified by silica gel column chromatography (eluent; chloroform:methanol=1:0-9:1) to obtain 5-(3-{[(2E)-4-chlorobuta-2-enoyl]amino}phenoxy)-6-isopropyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (125 mg) as a solid.

Workup

  1. temperaturecooling
  2. customprepared above under ice-
  3. temperaturecooling
  4. stirringby stirring at room temperature overnight
  5. filtrationthe precipitated solid was collected by filtration
  6. customdried under reduced pressure
  7. customThe obtained solid was purified by silica gel column chromatography (eluent; chloroform:methanol=1:0-9:1)

Sources & evidence

ORD record
ord-e976c7567dbe40a1a734a39e7a32bcdb
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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