Trifluoroacetic acid → (R)-1-(2-chloro-7-methylquinazolin-4-yl)pyrrolidin-3-amine

HRID 2406194Notes

Reaction equation

HRID 2406194 reaction equation
[Cl:1][C:2]1[N:11]=[C:10]([N:12]2[CH2:16][CH2:15][C@@H:14]([NH:17]C(=O)OC(C)(C)C)[CH2:13]2)[C:9]2[C:4](=[CH:5][C:6]([CH3:25])=[CH:7][CH:8]=2)[N:3]=1.FC(F)(F)C(O)=O>ClCCl>[Cl:1][C:2]1[N:11]=[C:10]([N:12]2[CH2:16][CH2:15][C@@H:14]([NH2:17])[CH2:13]2)[C:9]2[C:4](=[CH:5][C:6]([CH3:25])=[CH:7][CH:8]=2)[N:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59758791(R)-tert-butyl 1-(2-chloro-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate

Product 1

HCID 59758793(R)-1-(2-chloro-7-methylquinazolin-4-yl)pyrrolidin-3-amineYield 94.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-tert-butyl 1-(2-chloro-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate (1.17 g, 3.22 mmol) in 50 mL of dichloromethane was added 10 mL of trifluoroacetic acid in portions. The reaction was stirred at RT for 1 hour. The solvent was evaporated, and the residue was dissolved in 20 mL of dichloromethane, cooled to 0° C., and quenched with 1M NaOH until basic. After partitioning between CH2Cl2 and H2O, the mixture was separated and the aqueous layer was twice extracted with CH2Cl2. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification via silica gel chromatography using 0%-10% EtOAc in DCM gave (R)-1-(2-chloro-7-methylquinazolin-4-yl)pyrrolidin-3-amine (800 mg, 94% yield). LC/MS: m/z 262.9 (M+H)+ at 0.79 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue was dissolved in 20 mL of dichloromethane
  3. temperaturecooled to 0° C.
  4. customquenched with 1M NaOH until basic
  5. customAfter partitioning between CH2Cl2 and H2O
  6. customthe mixture was separated
  7. extractionthe aqueous layer was twice extracted with CH2Cl2
  8. dry with materialThe combined organic layers were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-68bf2af63b824b4187b4187e8250dd97
Source dataset
uspto-grants-2014_08
Patent number
US08809353B2

Reaction notes

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