Trifluoroacetic acid → HCID 77981604, compound

HRID 716060Notes

Reaction equation

HRID 716060 reaction equation
[C:1]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([CH:23]=[C:24]([C:27]4[S:28][CH:29]=[CH:30][N:31]=4)[C:25]#[N:26])=[CH:19][CH:18]=3)[N:14]=2)[N:9](COCC[Si](C)(C)C)[CH:8]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].C(O)(C(F)(F)F)=O.C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(O)C>[C:1]([C:7]1[C:15]2[C:10](=[N:11][CH:12]=[C:13]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([CH:23]=[C:24]([C:27]4[S:28][CH:29]=[CH:30][N:31]=4)[C:25]#[N:26])=[CH:19][CH:18]=3)[N:14]=2)[NH:9][CH:8]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 77981592HCID 77981592, compound

Product 1

HCID 77981604HCID 77981604, compoundYield 50.7%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a 25 ml one necked round bottom flask, 3-(4-(7-pivaloyl-5-((2-(trimethylsilyl)-ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)phenyl)-2-(thiazol-2-yl)acrylonitrile (0.09 g, 0.000161 mol) was taken in CH2Cl2 (10 ml) followed by dropwise addition of TFA (2.0 ml) at 0°-5° C. and the reaction was allowed to stir at room temperature for 24 hr. After completion of the reaction, the pH of the solution was adjusted to neutral by the addition of saturated sodium bicarbonate solution and the product was extracted with CH2Cl2. The combined organic layer was dried over anhy. sodium sulphate and concentrated to obtain crude mixture which was dissolved in ethanol (10 ml) and NaOAc.3H2O (0.219 g, 0.00161 moles) was added and the reaction mixture was stirred it at room temperature for 20 hr. Ethanol was removed and the reaction mixture was diluted with water, followed by extraction with ethyl acetate. The combined organic layers were dried over sodium sulphate, concentrated to afford crude product which was purified using column purification by eluting the compound with 50% ethyl acetate in hexanes to yield 35.0 mg of 3-(4-(7-pivaloyl-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)phenyl)-2-(thiazol-2-yl)acrylonitrile.

Workup

  1. customAfter completion of the reaction
  2. extractionthe product was extracted with CH2Cl2
  3. customThe combined organic layer was dried over anhy
  4. concentrationsodium sulphate and concentrated
  5. customto obtain crude mixture which
  6. stirringthe reaction mixture was stirred it at room temperature for 20 hr
  7. customEthanol was removed
  8. additionthe reaction mixture was diluted with water
  9. extractionfollowed by extraction with ethyl acetate
  10. dry with materialThe combined organic layers were dried over sodium sulphate
  11. concentrationconcentrated
  12. customto afford crude product which
  13. customwas purified
  14. customcolumn purification
  15. washby eluting the compound with 50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-704e7a55c5d44f63a616fb5957a57519
Source dataset
uspto-grants-2015_11
Patent number
US09187487B2

Reaction notes

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