Trifluoroacetic acid → Methyl 2-(2-(2-(2-((2-methyl-4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate

HRID 705776Notes

Reaction equation

HRID 705776 reaction equation
CS([C:5]1[N:10]=[C:9]([CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH2:19][C:20]([O:22][CH3:23])=[O:21])[C:8]([C:24]([F:27])([F:26])[F:25])=[CH:7][N:6]=1)(=O)=O.[NH2:28][C:29]1[CH:34]=[CH:33][C:32]([CH:35]2[CH2:40][CH2:39][N:38](C(OC(C)(C)C)=O)[CH2:37][CH2:36]2)=[CH:31][C:30]=1[CH3:48].C(O)(C(F)(F)F)=O>>[CH3:48][C:30]1[CH:31]=[C:32]([CH:35]2[CH2:36][CH2:37][NH:38][CH2:39][CH2:40]2)[CH:33]=[CH:34][C:29]=1[NH:28][C:5]1[N:10]=[C:9]([CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH2:19][C:20]([O:22][CH3:23])=[O:21])[C:8]([C:24]([F:27])([F:26])[F:25])=[CH:7][N:6]=1

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 68282869Methyl 2-(2-(2-(2-(methylsulfonyl)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetateHCID 68283578Tert-butyl 4-(4-amino-3-methylphenyl)piperidine-1-carboxylate

Product 1

HCID 68283581Methyl 2-(2-(2-(2-((2-methyl-4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate

Procedure

A solution of methyl 2-(2-(2-(2-(methylsulfonyl)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate (I15) (450 mg, 1.11 mmol), tert-butyl 4-(4-amino-3-methylphenyl)piperidine-1-carboxylate (I53) (390 mg, 1.34 mmol) and TFA (0.25 mL) in 2,2,2-TFE (3 mL) was heated at 120° C. under microwave irradiation for 30 minutes. The resulting mixture was adsorbed onto silica gel and chromatographed (0-50% MeOH/DCM) to give the titie compound (I54) (478 mg, 83%) as a viscous liquid; 1H NMR (400 MHz, CDCl3) δ 9.14 (bs, 1H), 8.76 (bs, 1H), 8.51 (s, 1H), 7.58 (d, J=8.2 Hz, 1H), 7.21 (ddt, J=10.7, 7.4, 4.3 Hz, 4H), 7.15-7.06 (m, 1H), 3.65 (s, 2H), 3.60 (d, J=12.6 Hz, 2H), 3.49 (s, 3H), 3.15-3.02 (m, 6H), 2.87-2.71 (m, 1H), 2.32 (s, 3H), 2.07 (d, J=7.8 Hz, 4H). LCMS Method C: rt 5.24 min; m/z 513.2 [M+1]+.

Workup

  1. customchromatographed (0-50% MeOH/DCM)
  2. customto give the titie compound (I54) (478 mg, 83%) as a viscous liquid
  3. customrt 5.24 min

Sources & evidence

ORD record
ord-144d6f00f5384eb0864f6da02815cb34
Source dataset
uspto-grants-2015_11
Patent number
US09174946B2

Reaction notes

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