Trifluoroacetic acid → (3R)-3-Amino-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-1-methyl-pyrrolidin-2-one

HRID 626900Notes

Reaction equation

HRID 626900 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([O:10][C:11]1[CH:12]=[CH:13][C:14]([F:42])=[C:15]([C:17]2[CH:22]=[C:21]([CH3:23])[N:20]=[C:19]([C:24]#[C:25][CH2:26][C@@:27]3([NH:34]C(=O)OC(C)(C)C)[CH2:31][CH2:30][N:29]([CH3:32])[C:28]3=[O:33])[N:18]=2)[CH:16]=1)[CH3:9].C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[NH2:34][C@:27]1([CH2:26][C:25]#[C:24][C:19]2[N:18]=[C:17]([C:15]3[CH:16]=[C:11]([O:10][CH2:8][CH3:9])[CH:12]=[CH:13][C:14]=3[F:42])[CH:22]=[C:21]([CH3:23])[N:20]=2)[CH2:31][CH2:30][N:29]([CH3:32])[C:28]1=[O:33]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 90015138tert-butyl N-[(3R)-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-1-methyl-2-oxo-pyrrolidin-3-yl]carbamate

Product 1

HCID 90015517(3R)-3-Amino-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-1-methyl-pyrrolidin-2-oneYield 93.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (3 mL, 40.39 mmol) was added to a solution of tert-butyl N-[(3R)-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-1-methyl-2-oxo-pyrrolidin-3-yl]carbamate (which may be prepared as described in Description 18) (605 mg, 1.25 mmol) in DCM (15 mL) at 20° C. and the reaction was stirred for 1 hour. Solid K2CO3 was added to quench the TFA present (care: gas evolved) and the resultant solid was filtered off and washed five times with DCM. The solvent was evaporated to give the (3R)-3-amino-3-[3-[4-(5-ethoxy-2-fluoro-phenyl)-6-methyl-pyrimidin-2-yl]prop-2-ynyl]-1-methyl-pyrrolidin-2-one (D19) (447 mg, 1.1688 mmol, 93.2% yield) as a yellow oil.

Workup

  1. customto quench the TFA present (care: gas evolved)
  2. filtrationthe resultant solid was filtered off
  3. washwashed five times with DCM
  4. customThe solvent was evaporated

Sources & evidence

ORD record
ord-93688221b55c4d5499705a4b1349a498
Source dataset
uspto-grants-2016_04
Patent number
US09309254B2

Reaction notes

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