Acetonitrile → HCID 71667533, compound

HRID 1526263Notes

Reaction equation

HRID 1526263 reaction equation
Cl.[CH3:2][N:3]([CH3:10])[CH2:4]/[CH:5]=[CH:6]/[C:7](O)=[O:8].C(#N)C.C(Cl)(=O)C(Cl)=O.[NH2:20][C:21]1[CH:22]=[C:23]([CH:50]=[CH:51][CH:52]=1)[O:24][C:25]1[N:26]=[C:27]([NH:36][C:37]2[CH:42]=[CH:41][C:40]([N:43]3[CH2:48][CH2:47][N:46]([CH3:49])[CH2:45][CH2:44]3)=[CH:39][CH:38]=2)[C:28]([C:33]([NH2:35])=[O:34])=[N:29][C:30]=1[CH2:31][CH3:32]>C(OCC)(=O)C.CN1CCCC1=O.CN(C)C=O>[CH3:2][N:3]([CH3:10])[CH2:4]/[CH:5]=[CH:6]/[C:7]([NH:20][C:21]1[CH:22]=[C:23]([CH:50]=[CH:51][CH:52]=1)[O:24][C:25]1[N:26]=[C:27]([NH:36][C:37]2[CH:38]=[CH:39][C:40]([N:43]3[CH2:44][CH2:45][N:46]([CH3:49])[CH2:47][CH2:48]3)=[CH:41][CH:42]=2)[C:28]([C:33]([NH2:35])=[O:34])=[N:29][C:30]=1[CH2:31][CH3:32])=[O:8]

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 65578Oxalyl chlorideHCID 45358758(2E)-4-(Dimethylamino)-2-butenoic acid hydrochlorideHCID 117667188HCID 117667188, compound

Product 1

HCID 71667533HCID 71667533, compoundYield 45.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a mixture of trans-4-dimethylaminocrotonic acid hydrochloride (113 mg) and acetonitrile (1.9 mL) were added oxalyl dichloride (55 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-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (190 mg) and N-methylpyrrolidone (3.8 mL) was added a solution of the acid chloride prepared above under ice-cooling, followed by stirring at room temperature overnight. The reaction mixture was diluted with ethyl acetate, and then washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine. The organic phase was dried over anhydrous magnesium sulfate and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-100:10:1). Ethyl acetate was added thereto and the precipitated solid was collected by filtration and then dried under reduced pressure to obtain 5-(3-{[(2E)-4-(dimethylamino)buta-2-enoyl]amino}phenoxy)-6-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (107 mg) as a pale yellow solid.

Workup

  1. temperaturecooling
  2. customprepared above under ice-
  3. temperaturecooling
  4. stirringby stirring at room temperature overnight
  5. washwashed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine
  6. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-100:10:1)
  9. additionEthyl acetate was added
  10. filtrationthe precipitated solid was collected by filtration
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-9b823344106846078ef3bf011ec23928
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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