Trifluoroacetic acid → 2-(2-(2-(2-((4-(Piperidin-3-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetamide

HRID 1485289Notes

Reaction equation

HRID 1485289 reaction equation
[NH2:1][C:2](=[O:42])[CH2:3][C:4]1[C:5]([CH2:10][CH2:11][C:12]2[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][N:15]=[C:14]([NH:22][C:23]3[CH:28]=[CH:27][C:26]([CH:29]4[CH2:34][CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30]4)=[CH:25][CH:24]=3)[N:13]=2)=[N:6][CH:7]=[CH:8][CH:9]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:31]1[CH2:32][CH2:33][CH2:34][CH:29]([C:26]2[CH:27]=[CH:28][C:23]([NH:22][C:14]3[N:13]=[C:12]([CH2:11][CH2:10][C:5]4[C:4]([CH2:3][C:2]([NH2:1])=[O:42])=[CH:9][CH:8]=[CH:7][N:6]=4)[C:17]([C:18]([F:20])([F:19])[F:21])=[CH:16][N:15]=3)=[CH:24][CH:25]=2)[CH2:30]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71209278tert-Butyl 3-(4-((4-(2-(3-(2-amino-2-oxoethyl)pyridin-2-yl)ethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Product 1

HCID 601649122-(2-(2-(2-((4-(Piperidin-3-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyridin-3-yl)acetamideYield 95.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 3-(4-((4-(2-(3-(2-amino-2-oxoethyl)pyridin-2-yl)ethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I150) (23 mg, 0.039 mmol) in DCM (7 mL) was added TFA (1 mL). The resulting solution was stirred at room temperature for 17 hours then the volatiles were removed in vacuo. The residue was partitioned between ethyl acetate (50 mL) and a 2.0 M solution of NaOH (50 mL) then the organic layer was washed with water (50 mL), brine (50 mL) and dried over MgSO4 before being evaporated in vacuo to give the title compound (39) (18 mg, 94%) as a white solid; 1H NMR (400 MHz, d4-MeOH) δ 8.52 (s, 1H), 8.37 (dd, J=4.9, 1.6 Hz, 1H), 7.67 (dd, J=7.7, 1.6 Hz, 1H), 7.61 (d, J=8.6 Hz, 2H), 7.27-7.17 (m, 3H), 3.68 (s, 2H), 3.39-3.32 (m, 2H), 3.27 (d, J=8.7 Hz, 2H), 3.21-3.14 (m, 2H), 2.82-2.70 (m, 3H), 2.07-1.94 (m, 1H), 1.94-1.83 (m, 1H), 1.80-1.64 (m, 2H). LCMS Method C: rt 4.12 min, m/z=485.1 [M+H]+, 483.1 [M−H]−.

Workup

  1. customthe volatiles were removed in vacuo
  2. customThe residue was partitioned between ethyl acetate (50 mL)
  3. washa 2.0 M solution of NaOH (50 mL) then the organic layer was washed with water (50 mL), brine (50 mL)
  4. dry with materialdried over MgSO4
  5. custombefore being evaporated in vacuo

Sources & evidence

ORD record
ord-abc222607859431ba77d89c5b7760b3a
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

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