Potassium Carbonate → tert-butyl 5-(2-(3-((R)-pyrrolidine-2-carboxamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate

HRID 1808404Notes

Reaction equation

HRID 1808404 reaction equation
FC(F)(F)C([N:5]1[CH2:9][CH2:8][CH2:7][C@@H:6]1[C:10]([NH:12][C:13]1[CH:14]=[C:15]([C:19]2[N:28]=[C:27]([NH:29][C:30]3[CH:31]=[C:32]4[C:36](=[CH:37][CH:38]=3)[N:35]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[N:34]=[CH:33]4)[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:20]=2)[CH:16]=[CH:17][CH:18]=1)=[O:11])=O.C([O-])([O-])=O.[K+].[K+]>CO.O>[NH:5]1[CH2:9][CH2:8][CH2:7][C@@H:6]1[C:10]([NH:12][C:13]1[CH:14]=[C:15]([C:19]2[N:28]=[C:27]([NH:29][C:30]3[CH:31]=[C:32]4[C:36](=[CH:37][CH:38]=3)[N:35]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[N:34]=[CH:33]4)[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:20]=2)[CH:16]=[CH:17][CH:18]=1)=[O:11]

Participants

5

Reactant 2

HCID 11430Potassium CarbonateHCID 59361903tert-butyl 5-(2-(3-((R)-1-(2,2,2-trifluoroacetyl)pyrrolidine-2-carboxamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate

Product 1

HCID 59361907tert-butyl 5-(2-(3-((R)-pyrrolidine-2-carboxamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a suspension of tert-butyl 5-(2-(3-((R)-1-(2,2,2-trifluoroacetyl)-pyrrolidine-2-carboxamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate (100 mg, 0.15 mmol) in MeOH (5.7 mL) and H2O (345 mL) was added K2CO3 (108 mg, 0.78 mmol). Reaction mixture was refluxed for 2 h. Cooled to RT temperature and concentrated in vacuo. The residue was dissolved in EtOAc and extracted with H2O (3×). Dried the organic layer under Na2SO4 and concentrated in vacuo. The aqueous layer was basicified with 1 N NaOH, extracted with CHCl3 (3×), dried under Na2SO4 and concentrated in vacuo. The two organic layers were combined to afford tert-butyl 5-(2-(3-((R)-pyrrolidine-2-carboxamido)phenyl)quinazolin-4-ylamino)-1H-indazole-1-carboxylate. (65 mg, 79%).

Workup

  1. customReaction mixture
  2. temperaturewas refluxed for 2 h
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in EtOAc
  5. extractionextracted with H2O (3×)
  6. customDried the organic layer under Na2SO4
  7. concentrationconcentrated in vacuo
  8. extractionextracted with CHCl3 (3×)
  9. customdried under Na2SO4
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b1e796ecaf73466b8c9c9bc878a6cb1c
Source dataset
uspto-grants-2013_01
Patent number
US08357693B2

Reaction notes

Loading…