Ammonia → (+/-)-5-{6-[(Acetyl-pyrrolidin-3-yl-amino)-methyl]-pyrimidin-4-yloxy}-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

HRID 453188Notes

Reaction equation

HRID 453188 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][CH:10]([N:13]([C:44](=[O:46])[CH3:45])[CH2:14][C:15]2[CH:20]=[C:19]([O:21][C:22]3[CH:23]=[C:24]4[C:28](=[CH:29][CH:30]=3)[N:27]([C:31](=[O:43])[NH:32][C:33]3[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([F:42])([F:41])[F:40])[CH:34]=3)[CH:26]=[CH:25]4)[N:18]=[CH:17][N:16]=2)[CH2:9]1)=O)(C)(C)C.C(Cl)Cl.C(O)(C(F)(F)F)=O.N>CO.C(Cl)Cl>[F:42][C:39]([F:40])([F:41])[C:35]1[CH:34]=[C:33]([NH:32][C:31]([N:27]2[C:28]3[C:24](=[CH:23][C:22]([O:21][C:19]4[CH:20]=[C:15]([CH2:14][N:13]([C:44](=[O:46])[CH3:45])[CH:10]5[CH2:11][CH2:12][NH:8][CH2:9]5)[N:16]=[CH:17][N:18]=4)=[CH:30][CH:29]=3)[CH:25]=[CH:26]2)=[O:43])[CH:38]=[CH:37][CH:36]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 59394656(+/-)-3-(Acetyl-{6-[1-(3-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-pyrimidin-4-ylmethyl}-amino)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 59394774(+/-)-5-{6-[(Acetyl-pyrrolidin-3-yl-amino)-methyl]-pyrimidin-4-yloxy}-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

(±)-3-(Acetyl-{6-[1-(3-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-pyrimidin-4-ylmethyl}-amino)-pyrrolidine-1-carboxylic acid tert-butyl ester (30 mg, 0.056 mmol) is stirred in a solution of DCM (2 mL) and TFA (0.5 mL) overnight. After removal of the solvents, the residue is quenched with saturated aqueous sodium bicarbonate. The mixture is extracted with EtOAc (3×). The combined organic layers are washed with water and brine and the organic layer is dried with Na2SO4, filtered, and condensed. The residue is then separated by FCC (0-10%, 2 mol NH3 in MeOH/DCM) to provide the title compound. MS (ESI) m/z 538.9 (M+1).

Workup

  1. customAfter removal of the solvents
  2. customthe residue is quenched with saturated aqueous sodium bicarbonate
  3. extractionThe mixture is extracted with EtOAc (3×)
  4. washThe combined organic layers are washed with water and brine
  5. dry with materialthe organic layer is dried with Na2SO4
  6. filtrationfiltered
  7. customcondensed

Sources & evidence

ORD record
ord-a048863385e74cba9abc2054f473f5d0
Source dataset
uspto-grants-2013_07
Patent number
US08492393B2

Reaction notes

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