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

HRID 1485187Notes

Reaction equation

HRID 1485187 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C:9](=[O:50])[CH:10]([C:12]1[CH:49]=[CH:48][CH:47]=[CH:46][C:13]=1[CH2:14][CH2:15][C:16]1[C:21]([C:22]([F:25])([F:24])[F:23])=[CH:20][N:19]=[C:18]([NH:26][C:27]2[CH:32]=[CH:31][C:30]([CH:33]3[CH2:38][CH2:37][N:36](C(OC(C)(C)C)=O)[CH2:35][CH2:34]3)=[CH:29][CH:28]=2)[N:17]=1)[CH3:11].C1CCCCC1>C(Cl)Cl.CCOC(C)=O>[NH:36]1[CH2:37][CH2:38][CH:33]([C:30]2[CH:29]=[CH:28][C:27]([NH:26][C:18]3[N:17]=[C:16]([CH2:15][CH2:14][C:13]4[CH:46]=[CH:47][CH:48]=[CH:49][C:12]=4[CH:10]([CH3:11])[C:9]([NH2:8])=[O:50])[C:21]([C:22]([F:25])([F:24])[F:23])=[CH:20][N:19]=3)=[CH:32][CH:31]=2)[CH2:34][CH2:35]1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 8078CyclohexaneHCID 68283002tert-Butyl 4-(4-((4-(2-(1-amino-1-oxopropan-2-yl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Product 1

HCID 682824902-(2-(2-(2-((4-(Piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)propanamideYield 47%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Trifluoroacetic acid (0.417 mL, 5.46 mmol) was added to a solution of tert-butyl 4-(4-((4-(2-(1-amino-1-oxopropan-2-yl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I55) (65.2 mg, 0.109 mmol) in dry DCM (8 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 (20 mL) and 2 M NaOH (20 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic layers were washed with water (20 mL), brine (20 mL), dried over Na2SO4. After filtration the solvent was removed under reduced pressure to give a pale yellow solid which was dissolved in EtOAc (2 mL) to which was added cyclohexane (10 mL). The resulting precipitate was collected by filtration to afford the title compound (I2) (25 mg, 47%) as an off-white solid; 1H NMR (400 MHz, d6-DMSO) δ 10.14 (s, 1H), 8.67 (s, 1H), 7.68-7.65 (m, 2H), 7.42-7.34 (m, 1H), 7.26-7.12 (m, 6H), 6.87 (s, 1H), 3.86 (q, J=7.0 Hz, 1H), 3.44-3.18 (m, peaks obscured by water peak), 3.14-2.95 (m, 5H), 2.64-2.46 (m, peaks obscured by DMSO), 1.68 (d, J=13.0 Hz, 2H), 1.49 (qd, J=12.1, 2.4 Hz, 2H), 1.31 (d, J=7.0 Hz, 3H). LCMS Method C: rt 4.91 min; m/z 498 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe residue partitioned between EtOAc (20 mL) and 2 M NaOH (20 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (2×20 mL)
  5. washThe combined organic layers were washed with water (20 mL), brine (20 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationAfter filtration the solvent
  8. customwas removed under reduced pressure
  9. customto give a pale yellow solid which
  10. filtrationThe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-45a73e8b3e1141a0b24048c3305107f0
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

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