Trifluoroacetic acid → 2-cyano-3-(4-(7-pivaloyl-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)phenyl)acrylamide

HRID 716033Notes

Reaction equation

HRID 716033 reaction equation
[C:1]([C:3](=[CH:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]2[N:16]=[C:17]3[C:23]([C:24](=[O:29])[C:25]([CH3:28])([CH3:27])[CH3:26])=[CH:22][N:21](COCC[Si](C)(C)C)[C:18]3=[N:19][CH:20]=2)=[CH:10][CH:9]=1)[C:4]([NH2:6])=[O:5])#[N:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:1]([C:3](=[CH:7][C:8]1[CH:9]=[CH:10][C:11]([NH:14][C:15]2[N:16]=[C:17]3[C:23]([C:24](=[O:29])[C:25]([CH3:27])([CH3:26])[CH3:28])=[CH:22][NH:21][C:18]3=[N:19][CH:20]=2)=[CH:12][CH:13]=1)[C:4]([NH2:6])=[O:5])#[N:2]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 710142392-cyano-3-(4-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)phenyl)acrylamide

Product 1

HCID 710142842-cyano-3-(4-(7-pivaloyl-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)phenyl)acrylamideYield 25.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a 25 ml one necked round bottom flask 2-cyano-3-(4-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)phenyl)acrylamide (0.1 g, 0.0002 mole) was taken in CH2Cl2 (10 ml). To this reaction mixture TFA (2.0 ml) was added dropwise at 0° C. After completion of the addition, the reaction mixture was warmed up to RT and then stirred for 16 hr. After completion of the reaction, CH2Cl2 was distilled out and the pH was adjusted to 8 to 9 using saturated NaHCO3 solution at 5° C. The reaction mixture was stirred for 15 min, solid was filtered, washed with n-pentane and dried. In a 25 ml RBF, dried solid was taken in ethanol and NaOAc. 3H2O (0.27 g, 0.002 mole) was added at RT. The reaction mixture was stirred for 20 hr at RT, diluted with ethyl acetate and distilled out under vacuum. To the resultant residual solid water was added, the mixture was stirred for 15 min, filtered, wash with water and n-pentane was added. The product was filtered and dried under vacuum to yield 20 mg of 2-cyano-3-(4-(7-pivaloyl-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)phenyl)acrylamide.

Workup

  1. additionAfter completion of the addition
  2. distillationwas distilled out
  3. customwas adjusted to 8 to 9 using saturated NaHCO3 solution at 5° C
  4. stirringThe reaction mixture was stirred for 15 min
  5. filtrationsolid was filtered
  6. washwashed with n-pentane
  7. customdried
  8. customIn a 25 ml RBF, dried solid
  9. addition3H2O (0.27 g, 0.002 mole) was added at RT
  10. stirringThe reaction mixture was stirred for 20 hr at RT
  11. additiondiluted with ethyl acetate
  12. distillationdistilled out under vacuum
  13. additionTo the resultant residual solid water was added
  14. stirringthe mixture was stirred for 15 min
  15. filtrationfiltered
  16. washwash with water and n-pentane
  17. additionwas added
  18. filtrationThe product was filtered
  19. customdried under vacuum

Sources & evidence

ORD record
ord-18b81e13e99747c189f87dfce67f116c
Source dataset
uspto-grants-2015_11
Patent number
US09187487B2

Reaction notes

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