Trifluoroacetic acid → 2-Cyano-4-methylpent-2-enoic acid

HRID 1778438Notes

Reaction equation

HRID 1778438 reaction equation
NC1N=CN=C2N(CC3CN(C(OC(C)(C)C)=O)C3)N=[C:10]([C:11]3[CH:16]=CC(OC4C=CC=CC=4)=C[C:12]=3F)C=12.[C:37]([OH:43])([C:39](F)(F)F)=[O:38].[NH:44]1CC(CN2C3=NC=NC(N)=C3C(C3C=CC(OC4C=CC=CC=4)=CC=3F)=N2)[CH2:45]1>C(Cl)Cl>[C:45]([C:39](=[CH:10][CH:11]([CH3:16])[CH3:12])[C:37]([OH:43])=[O:38])#[N:44]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 90001546HCID 90001546, compoundHCID 90001912HCID 90001912, compound

Product 1

HCID 2925472-Cyano-4-methylpent-2-enoic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 3-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidine-1-carboxylate (780 mg) in DCM (2 mL) was cooled in an ice bath. To this was added TFA (4 mL, 1.59 mmol), the ice bath was removed and the reaction mixture was stirred at room temperature for 1 hour, checking reaction by TLC and LC-MS. After two hours the solvent was removed, and to the residue was added water. The water layer was extracted with by EtOAc and the combined organic layer washed with 2N HCl. The combined aqueous layer was adjusted with NaOH to pH 9-10, extracted with EtOAc, and the combined organic layer washed with brine, dried over Na2SO4 and filtered. The solvent was removed to obtain 2-cyano-4-methyl-pent-2-enoic acid (48.12 mg, 0.350 mmol), 1-(azetidin-3-ylmethyl)-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-amine which was used in the next step without further purification.

Workup

  1. customthe ice bath was removed
  2. customreaction by TLC and LC-MS
  3. customAfter two hours the solvent was removed
  4. additionto the residue was added water
  5. extractionThe water layer was extracted with by EtOAc
  6. washthe combined organic layer washed with 2N HCl
  7. extractionextracted with EtOAc
  8. washthe combined organic layer washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. customThe solvent was removed

Sources & evidence

ORD record
ord-be758d1fd1ab41aa926b6f23f515e6e9
Source dataset
uspto-grants-2016_02
Patent number
US09266895B2

Reaction notes

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