Acryloyl chloride → HCID 71667534, compound

HRID 1526261Notes

Reaction equation

HRID 1526261 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:31]=[CH:32][CH:33]=1)[O:5][C:6]1[N:7]=[C:8]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([N:24]3[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]3)=[CH:20][CH:19]=2)[C:9]([C:14]([NH2:16])=[O:15])=[N:10][C:11]=1[CH2:12][CH3:13].C(N(C(C)C)CC)(C)C.[C:43](Cl)(=[O:46])[CH:44]=[CH2:45]>C(Cl)(Cl)Cl>[C:43]([NH:1][C:2]1[CH:3]=[C:4]([CH:31]=[CH:32][CH:33]=1)[O:5][C:6]1[N:7]=[C:8]([NH:17][C:18]2[CH:19]=[CH:20][C:21]([N:24]3[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]3)=[CH:22][CH:23]=2)[C:9]([C:14]([NH2:16])=[O:15])=[N:10][C:11]=1[CH2:12][CH3:13])(=[O:46])[CH:44]=[CH2:45]

Participants

5

Reactant 3

HCID 13140Acryloyl chloride2×HCID 81531DiisopropylethylamineHCID 117667188HCID 117667188, compound

Product 1

HCID 71667534HCID 71667534, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a mixture of 5-(3-aminophenoxy)-6-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (2 g), diisopropylethylamine (1.53 mL), and chloroform (100 mL) was added acryloyl chloride (508 μL) under ice-cooling, followed by stirring for 1 hour. Acryloyl chloride (363 μL) was added thereto, followed by stirring for 1 hour. The mixture was subject to liquid separation by the addition of chloroform and a saturated aqueous sodium hydrogen carbonate solution, and the organic phase was washed with saturated brine and then dried over anhydrous magnesium sulfate. The solvent was concentrated and the obtained residue was purified by silica gel column chromatography (chloroform:methanol:28% aqueous ammonia=1:0:0-200:10:1). Ethyl acetate was added thereto, the solid was collected by filtration and then dried under reduced pressure to obtain 5-[3-(acryloylamino)phenoxy]-6-ethyl-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (1.6 g) as a pale yellow solid.

Workup

  1. temperaturecooling
  2. stirringby stirring for 1 hour
  3. customThe mixture was subject to liquid separation by the addition of chloroform
  4. washa saturated aqueous sodium hydrogen carbonate solution, and the organic phase was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationThe solvent was concentrated
  7. customthe obtained residue was purified by silica gel column chromatography (chloroform:methanol:28% aqueous ammonia=1:0:0-200:10:1)
  8. additionEthyl acetate was added
  9. filtrationthe solid was collected by filtration
  10. customdried under reduced pressure

Sources & evidence

ORD record
ord-13440209699f49ffbb337fa9b43f392f
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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