Acryloyl chloride → HCID 117667603, compound

HRID 1526271Notes

Reaction equation

HRID 1526271 reaction equation
[OH:1][CH2:2][CH2:3][N:4]1[CH:8]=[C:7]([NH:9][C:10]2[C:11]([C:25]([NH2:27])=[O:26])=[N:12][C:13]([CH:22]([CH3:24])[CH3:23])=[C:14]([O:16][C@@H:17]3[CH2:21][CH2:20][NH:19][CH2:18]3)[N:15]=2)[CH:6]=[N:5]1.C(N(C(C)C)CC)(C)C.[C:37](Cl)(=[O:40])[CH:38]=[CH2:39]>C(Cl)(Cl)Cl>[C:37]([N:19]1[CH2:20][CH2:21][C@@H:17]([O:16][C:14]2[N:15]=[C:10]([NH:9][C:7]3[CH:6]=[N:5][N:4]([CH2:3][CH2:2][OH:1])[CH:8]=3)[C:11]([C:25]([NH2:27])=[O:26])=[N:12][C:13]=2[CH:22]([CH3:23])[CH3:24])[CH2:18]1)(=[O:40])[CH:38]=[CH2:39]

Participants

5

Reactant 3

HCID 13140Acryloyl chlorideHCID 81531DiisopropylethylamineHCID 117666841HCID 117666841, compound

Product 1

HCID 117667603HCID 117667603, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a mixture of 3-{[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]amino}-6-isopropyl-5-[(3R)-pyrrolidin-3-yloxy]pyrazine-2-carboxamide (476 mg), chloroform (5 mL), and diisopropylethylamine (867 μL) was added acryloyl chloride (226 μL) at 0° C., followed by stirring at the same temperature for 1 hour. The solvent of the reactant was evaporated, and then to the obtained residue were added tetrahydrofuran (5 mL) and a 1 M aqueous sodium hydroxide solution (5 mL), followed by stirring at 50° C. for 4 hours. After leaving to be cooled, the mixture was extracted by the addition of chloroform, and the organic phase was dried over anhydrous sodium sulfate. After concentration under reduced pressure, the obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=980:18:2-90:9:1), and then washed with diisopropyl ether to obtain 5-{[(3R)-1-acryloylpyrrolidin-3-yl]oxy}-3-{[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]amino}-6-isopropylpyrazine-2-carboxamide (343 mg) as a yellow solid.

Workup

  1. customThe solvent of the reactant was evaporated
  2. additionto the obtained residue were added tetrahydrofuran (5 mL)
  3. stirringby stirring at 50° C. for 4 hours
  4. customAfter leaving
  5. temperatureto be cooled
  6. extractionthe mixture was extracted by the addition of chloroform
  7. dry with materialthe organic phase was dried over anhydrous sodium sulfate
  8. concentrationAfter concentration under reduced pressure
  9. customthe obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol:28% aqueous ammonia=980:18:2-90:9:1)
  10. washwashed with diisopropyl ether

Sources & evidence

ORD record
ord-44aa676a24984ebe90af6438012f9860
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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