Dichloromethane → HCID 117666927, compound

HRID 1526270Notes

Reaction equation

HRID 1526270 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:17][C:18]2[CH:23]=[CH:22][C:21]([N:24]3[CH2:29][CH2:28][N:27]([CH3:30])[C@@H:26]([CH2:31][OH:32])[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].ClCCl.C(N(C(C)C)CC)(C)C.[C:48](Cl)(=[O:51])[CH:49]=[CH2:50]>C(Cl)(Cl)Cl.O>[C:48]([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:17][C:18]2[CH:19]=[CH:20][C:21]([N:24]3[CH2:29][CH2:28][N:27]([CH3:30])[C@@H:26]([CH2:31][OH:32])[CH2:25]3)=[CH:22][CH:23]=2)[C:9]([C:14]([NH2:16])=[O:15])=[N:10][C:11]=1[CH2:12][CH3:13])(=[O:51])[CH:49]=[CH2:50]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 117667464HCID 117667464, compound

Product 1

HCID 117666927HCID 117666927, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

To a mixture of 5-(3-aminophenoxy)-6-ethyl-3-({4-[(3R)-3-(hydroxymethyl)-4-methylpiperazin-1-yl]phenyl}amino)pyrazine-2-carboxamide (227 mg), dichloromethane (6.8 mL), and diisopropylethylamine (326 μL) was added acryloyl chloride (116 μL) at 0° C., followed by stirring at the same temperature for 2 hours. To the mixture were added water and chloroform, followed by liquid separation. The separated organic phase was washed with saturated brine and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the obtained residue were added tetrahydrofuran (4.5 mL) and a 1 M aqueous sodium hydroxide solution (1.1 mL), followed by stirring at room temperature overnight. The mixture was neutralized by the addition of 1 M hydrochloric acid, and extracted with a mixed solvent of chloroform:methanol (9:1) three times. The separated organic phase was washed with saturated brine and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol=9:1). A mixed solution of hexane:ethyl acetate (19:1) was added thereto, and the solid was collected by filtration, then washed, and dried under reduced pressure to obtain 5-[3-(acryloylamino)phenoxy]-6-ethyl-3-({4-[(3R)-3-(hydroxymethyl)-4-methylpiperazin-1-yl]phenyl}amino)pyrazine-2-carboxamide (27 mg) as a yellow solid.

Workup

  1. customfollowed by liquid separation
  2. washThe separated organic phase was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationAfter concentration under reduced pressure
  5. additionthe obtained residue were added tetrahydrofuran (4.5 mL)
  6. stirringby stirring at room temperature overnight
  7. additionThe mixture was neutralized by the addition of 1 M hydrochloric acid
  8. extractionextracted with a mixed solvent of chloroform:methanol (9:1) three times
  9. washThe separated organic phase was washed with saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. concentrationAfter concentration under reduced pressure
  12. customthe obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol=9:1)
  13. additionA mixed solution of hexane:ethyl acetate (19:1) was added
  14. filtrationthe solid was collected by filtration
  15. washwashed
  16. customdried under reduced pressure

Sources & evidence

ORD record
ord-51ee38cb7ec64dddb97aac360c8f56a0
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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