Trifluoroacetic acid → HCID 59394688, compound

HRID 45071Notes

Reaction equation

HRID 45071 reaction equation
C(O)(C(F)(F)F)=O.C(OC([N:15]1[CH2:24][CH2:23][C:22]2[C:21]([O:25][C:26]3[CH:27]=[C:28]4[C:32](=[CH:33][CH:34]=3)[N:31]([C:35](=[O:48])[NH:36][C:37]3[CH:42]=[C:41]([C:43]([F:46])([F:45])[F:44])[CH:40]=[CH:39][C:38]=3[F:47])[CH:30]=[CH:29]4)=[N:20][CH:19]=[N:18][C:17]=2[CH2:16]1)=O)(C)(C)C>C(Cl)Cl>[F:47][C:38]1[CH:39]=[CH:40][C:41]([C:43]([F:44])([F:45])[F:46])=[CH:42][C:37]=1[NH:36][C:35]([N:31]1[C:32]2[C:28](=[CH:27][C:26]([O:25][C:21]3[C:22]4[CH2:23][CH2:24][NH:15][CH2:16][C:17]=4[N:18]=[CH:19][N:20]=3)=[CH:34][CH:33]=2)[CH:29]=[CH:30]1)=[O:48]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 46224308HCID 46224308, compound

Product 1

HCID 59394688HCID 59394688, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (1 mL, 13.0 mmol) is added to a solution of 4-[1-(2-fluoro-5-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-5,8-dihydro-6H-pyrido[3,4-d]pyrimidine-7-carboxylic acid tert-butyl ester (0.125 g, 0.219 mmol) and DCM (2.5 mL). After 1 h the solution is concentrated in vacuo. The residue is taken up in MeOH and neutralized to pH 7 by the addition of NH4OH and the solution is separated via semi-prep HPLC (C18; 10-100% I/H2O with 0.1% NH4OH) to give 5-(5,6,7,8-Tetrahydro-pyrido[3,4-d]pyrimidin-4-yloxy)-indole-1-carboxylic acid (2-fluoro-5-trifluoromethyl-phenyl)-amide. MS (ESI) m/z 472.1 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 8.40 (s, 1 H), 8.25 (d, J=8.8 Hz, 1 H), 8.07 (d, J=3.8 Hz, 1 H), 8.03-8.07 (m, 1 H), 7.67-7.75 (m, 1 H), 7.56-7.64 (m, 1 H), 7.45 (d, J=2.5 Hz, 1 H), 7.11 (dd, J=9.0, 2.4 Hz, 1 H), 6.79 (d, J=3.5 Hz, 1 H), 3.83 (s, 2 H), 3.04 (t, J=5.8 Hz, 2 H), 2.73 (t, J=5.6 Hz, 2 H).

Workup

  1. concentrationAfter 1 h the solution is concentrated in vacuo
  2. additionThe residue is taken up in MeOH and neutralized to pH 7 by the addition of NH4OH
  3. customthe solution is separated via semi-prep HPLC (C18; 10-100% I/H2O with 0.1% NH4OH)

Sources & evidence

ORD record
ord-1304d761de434af288bae63405b4d7ef
Source dataset
uspto-grants-2013_09
Patent number
US08541432B2

Reaction notes

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