Trifluoroacetic acid → (3S)-3-amino-1-methyl-3-[3-[4-methyl-6-[4-(trifluoromethyl)phenyl]-pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-2-one

HRID 626891Notes

Reaction equation

HRID 626891 reaction equation
FC(F)(F)C(O)=O.[CH3:8][N:9]1[CH2:13][CH2:12][C@@:11]([NH:34]C(=O)OC(C)(C)C)([CH2:14][C:15]#[C:16][C:17]2[N:22]=[C:21]([CH3:23])[CH:20]=[C:19]([C:24]3[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=3)[N:18]=2)[C:10]1=[O:42]>C(Cl)Cl>[NH2:34][C@@:11]1([CH2:14][C:15]#[C:16][C:17]2[N:22]=[C:21]([CH3:23])[CH:20]=[C:19]([C:24]3[CH:25]=[CH:26][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:28][CH:29]=3)[N:18]=2)[CH2:12][CH2:13][N:9]([CH3:8])[C:10]1=[O:42]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90014756tert-butyl N-[(3S)-1-methyl-3-[3-[4-methyl-6-[4-(trifluoromethyl)-phenyl]pyrimidin-2-yl]prop-2-ynyl]-2-oxo-pyrrolidin-3-yl]carbamate

Product 1

HCID 90014870(3S)-3-amino-1-methyl-3-[3-[4-methyl-6-[4-(trifluoromethyl)phenyl]-pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-2-oneYield 89%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (5 mL, 67.31 mmol) was added to a solution of tert-butyl N-[(3S)-1-methyl-3-[3-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]prop-2-ynyl]-2-oxo-pyrrolidin-3-yl]carbamate (3.83 g, 7.84 mmol) (which may be prepared as described in Description 13a) in DCM (50 mL) at 20° C. and the reaction was stirred overnight. The reaction was concentrated and a further portion of trifluoroacetic acid (2 ml) added. Stirring was continued for 3 hrs then solid K2CO3 was added (care: gas evolved) and the mixture was diluted with water. The phases were separated and the organic layer was dried (Na2SO4). The solvent was evaporated to give (3S)-3-amino-1-methyl-3-[3-[4-methyl-6-[4-(trifluoromethyl)phenyl]pyrimidin-2-yl]prop-2-ynyl]pyrrolidin-2-one (D14a) (2.71 g, 6.9775 mmol, 89% yield) as a yellow oil. The NMR was the same as that produced by the R isomer in Description 14 but with some impurities present.

Workup

  1. concentrationThe reaction was concentrated
  2. additiona further portion of trifluoroacetic acid (2 ml) added
  3. stirringStirring
  4. waitwas continued for 3 hrs
  5. additionsolid K2CO3 was added (care: gas evolved)
  6. additionthe mixture was diluted with water
  7. customThe phases were separated
  8. dry with materialthe organic layer was dried (Na2SO4)
  9. customThe solvent was evaporated

Sources & evidence

ORD record
ord-9418069b28fa455d9ff737cc6d1e7339
Source dataset
uspto-grants-2016_04
Patent number
US09309254B2

Reaction notes

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