Water → HCID 117666949, compound

HRID 1526234Notes

Reaction equation

HRID 1526234 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].C(N([CH:42]([CH3:44])[CH3:43])CC)(C)C.ClCCl.[C:48](Cl)(=[O:51])[CH:49]=[CH2:50].[OH2:53]>C(Cl)(Cl)Cl>[C:48]([O:32][CH2:31][C@@H:26]1[CH2:25][N:24]([C:21]2[CH:20]=[CH:19][C:18]([NH:17][C:8]3[C:9]([C:14](=[O:15])[NH2:16])=[N:10][C:11]([CH2:12][CH3:13])=[C:6]([O:5][C:4]4[CH:33]=[CH:34][CH:35]=[C:2]([NH:1][C:44](=[O:53])[CH:42]=[CH2:43])[CH:3]=4)[N:7]=3)=[CH:23][CH:22]=2)[CH2:29][CH2:28][N:27]1[CH3:30])(=[O:51])[CH:49]=[CH2:50]

Participants

7

Reactant 5

HCID 962WaterHCID 6344DichloromethaneHCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 117667202HCID 117667202, compound

Product 1

HCID 117666949HCID 117666949, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a mixture of 5-(3-aminophenoxy)-6-ethyl-3-({4-[(3S)-3-(hydroxymethyl)-4-methylpiperazin-1-yl]phenyl}amino)pyrazine-2-carboxamide (210 mg), diisopropylethylamine (301 μL), and dichloromethane (6.3 mL) was added acryloyl chloride (107 μL) under ice-cooling, followed by stirring for 2 hours. To the reactant were added water and chloroform, followed by liquid separation. The organic phase was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol=95:5) to obtain {(2S)-4-[4-({6-[3-(acryloylamino)phenoxy]-3-carbamoyl-5-ethylpyrazin-2-yl}amino)phenyl]-1-methylpiperazin-2-yl}methyl acrylate (228 mg) as an amorphous substance.

Workup

  1. temperaturecooling
  2. customfollowed by liquid separation
  3. washThe organic phase was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol=95:5)

Sources & evidence

ORD record
ord-5473e7d102c1449f86da6748e62d017b
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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