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

HRID 1485181Notes

Reaction equation

HRID 1485181 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C:9](=[O:49])[CH2:10][C:11]1[CH:48]=[CH:47][CH:46]=[CH:45][C:12]=1[CH2:13][CH2:14][C:15]1[C:20]([C:21]([F:24])([F:23])[F:22])=[CH:19][N:18]=[C:17]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([CH:32]3[CH2:37][CH2:36][N:35](C(OC(C)(C)C)=O)[CH2:34][CH2:33]3)=[CH:28][CH:27]=2)[N:16]=1>C(Cl)Cl.C1CCCCC1>[NH:35]1[CH2:36][CH2:37][CH:32]([C:29]2[CH:28]=[CH:27][C:26]([NH:25][C:17]3[N:16]=[C:15]([CH2:14][CH2:13][C:12]4[CH:45]=[CH:46][CH:47]=[CH:48][C:11]=4[CH2:10][C:9]([NH2:8])=[O:49])[C:20]([C:21]([F:24])([F:23])[F:22])=[CH:19][N:18]=3)=[CH:31][CH:30]=2)[CH2:33][CH2:34]1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71209373tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Product 1

HCID 601646962-(2-(2-(2-((4-(Piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 84%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8078CyclohexaneSolvent

Procedure

Trifluoroacetic acid (0.595 mL, 7.78 mmol) was added to a solution of tert-butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I49) (90.8 mg, 0.156 mmol) in dry DCM (5 mL) under an atmosphere of nitrogen. The reaction was stirred at room temperature for 23 hours. The volatiles were removed in vacuo and the residue partitioned between EtOAc (30 mL) and 2M NaOH (30 mL). The two layers were separated and the aqueous layer was extracted with EtOAc (2×30 mL). The combined organic layers were washed with water (30 mL), brine (30 mL), dried over Na2SO4. After filtration the solvent was removed under reduced pressure to give a white solid which was suspended in DCM (2 mL) and cyclohexane (10 mL). The resulting precipitate was filtered to afford title compound (11) (63 mg, 84%) as an off-white solid; 1H NMR (400 MHz, d6-DMSO) δ 10.13 (s, 1H), 8.65 (s, 1H), 7.67-7.64 (m, 2H), 7.44 (s, 1H), 7.27-7.12 (m, 6H), 6.93 (s, 1H), 3.50 (s, 2H), 3.14-3.06 (m, 2H), 3.02-2.99 (m, 4H), 2.62-2.46 (m, peaks obscured by DMSO), 1.67 (d, J=11.4 Hz, 2H), 1.49 (qd, J=12.5, 3.9 Hz, 2H). LCMS Method C: rt 4.84 min; m/z 484 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe residue partitioned between EtOAc (30 mL) and 2M NaOH (30 mL)
  3. customThe two layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×30 mL)
  5. washThe combined organic layers were washed with water (30 mL), brine (30 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationAfter filtration the solvent
  8. customwas removed under reduced pressure
  9. customto give a white solid which
  10. filtrationThe resulting precipitate was filtered

Sources & evidence

ORD record
ord-fa1bc8eecbce43d493041477d0cf511f
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

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