Acryloyl chloride → 5-[3-(Acryloylamino)phenoxy]-6-(2-hydroxypropan-2-yl)-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide

HRID 1526266Notes

Reaction equation

HRID 1526266 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:33]=[CH:34][CH:35]=1)[O:5][C:6]1[N:7]=[C:8]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([N:26]3[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]3)=[CH:22][CH:21]=2)[C:9]([C:16]([NH2:18])=[O:17])=[N:10][C:11]=1[C:12]([OH:15])([CH3:14])[CH3:13].C(N(C(C)C)CC)(C)C.[C:45](Cl)(=[O:48])[CH:46]=[CH2:47].C(=O)([O-])O.[Na+].[OH-].[Na+]>O1CCCC1.C(Cl)(Cl)Cl>[C:45]([NH:1][C:2]1[CH:3]=[C:4]([CH:33]=[CH:34][CH:35]=1)[O:5][C:6]1[N:7]=[C:8]([NH:19][C:20]2[CH:21]=[CH:22][C:23]([N:26]3[CH2:27][CH2:28][N:29]([CH3:32])[CH2:30][CH2:31]3)=[CH:24][CH:25]=2)[C:9]([C:16]([NH2:18])=[O:17])=[N:10][C:11]=1[C:12]([OH:15])([CH3:13])[CH3:14])(=[O:48])[CH:46]=[CH2:47]

Participants

8

Reactant 5

HCID 13140Acryloyl chloride3×HCID 14798Sodium HydroxideHCID 81531Diisopropylethylamine2×HCID 516892Sodium BicarbonateHCID 1176673885-(3-Aminophenoxy)-6-(2-hydroxypropan-2-yl)-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide

Product 1

HCID 1176675365-[3-(Acryloylamino)phenoxy]-6-(2-hydroxypropan-2-yl)-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 5-(3-aminophenoxy)-6-(2-hydroxypropan-2-yl)-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (27 mg), diisopropylethylamine (29 μL), and chloroform (5 ml) was added acryloyl chloride (7 μL) under ice-cooling, followed by stirring for 30 minutes. Further acryloyl chloride (7 μL) was added, followed by stirring under ice-cooling for 30 minutes. Diisopropylethylamine (29 μl) and acryloyl chloride (7 μL) were added thereto, followed by stirring for 30 minutes under ice-cooling. A saturated aqueous sodium hydrogen carbonate solution (10 mL) and tetrahydrofuran (20 mL) were added thereto under ice-cooling, followed by stirring for 10 minutes under ice-cooling. To the reaction mixture was added a 1 M aqueous sodium hydroxide solution (2 mL), followed by stirring at room temperature for 30 minutes. The reaction mixture was subjected to liquid separation and to the organic phase was added silica gel. Then, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-200:10:1), washed with ethyl acetate, and the solid was collected by filtration and then dried under reduced pressure to obtain 5-[3-(acryloylamino)phenoxy]-6-(2-hydroxypropan-2-yl)-3-{[4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (18 mg) as a yellow solid.

Workup

  1. temperaturecooling
  2. stirringby stirring under ice-
  3. temperaturecooling for 30 minutes
  4. stirringby stirring for 30 minutes under ice-
  5. temperaturecooling
  6. temperatureunder ice-cooling
  7. stirringby stirring for 10 minutes under ice-
  8. temperaturecooling
  9. stirringby stirring at room temperature for 30 minutes
  10. customThe reaction mixture was subjected to liquid separation and to the organic phase
  11. additionwas added silica gel
  12. customThen, the solvent was evaporated under reduced pressure
  13. customThe residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=1:0:0-200:10:1)
  14. washwashed with ethyl acetate
  15. filtrationthe solid was collected by filtration
  16. customdried under reduced pressure

Sources & evidence

ORD record
ord-2683267da2d644c1aa63cab28dcc4a27
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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