Trifluoroacetic acid → (+/-)-5-[6-(Pyrrolidin-3-ylaminomethyl)-pyrimidin-4-yloxy]-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

HRID 45118Notes

Reaction equation

HRID 45118 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][CH:10]([NH:13][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(O)(C(F)(F)F)=O>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][NH:13][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

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59394560(+/-)-3-({6-[1-(3-Trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-pyrimidin-4-ylmethyl}-amino)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 59394310(+/-)-5-[6-(Pyrrolidin-3-ylaminomethyl)-pyrimidin-4-yloxy]-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(±)-3-({6-[1-(3-Trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-pyrimidin-4-ylmethyl}-amino)-pyrrolidine-1-carboxylic acid tert-butyl ester (20 mg, 3.30 mmol) is stirred in a solution of DCM (2 mL) and TFA (0.5 mL) overnight. After removal of solvents, the residue is quenched with saturated aqueous sodium bicarbonate. The mixture is then extracted with EtOAc (3×) and the combined organic layers are washed with water, brine, dried with Na2SO4, filtered, and condensed. The residue is purified by FCC (0-10% 2 M NH3 in MeOH/DCM) to provide the title compound. MS (ESI) m/z 496.8 (M+1); 1H NMR (400 MHz, MeOD) δ ppm 8.65 (s, 1 H), 8.36 (d, J=8.84 Hz, 1 H), 8.06 (s, 1 H), 7.95 (d, J=3.54 Hz, 1 H), 7.88 (s, 1 H), 7.57 (t, J=7.83 Hz, 1 H), 7.44 (d, J=7.83 Hz, 1 H), 7.42 (d, J=2.27 Hz, 1 H), 7.03-7.13 (m, 2 H), 6.75 (d, J=3.79 Hz, 1 H), 3.80-3.85 (m, 2 H), 2.81-3.02 (m, 3 H), 2.52-2.75 (m, 2 H), 2.19-2.35 (m, 2 H).

Workup

  1. customAfter removal of solvents
  2. customthe residue is quenched with saturated aqueous sodium bicarbonate
  3. extractionThe mixture is then extracted with EtOAc (3×)
  4. washthe combined organic layers are washed with water, brine
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. customcondensed
  8. customThe residue is purified by FCC (0-10% 2 M NH3 in MeOH/DCM)

Sources & evidence

ORD record
ord-30051dcbe0fd49f3b1544e466cf1fbb0
Source dataset
uspto-grants-2013_09
Patent number
US08541432B2

Reaction notes

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