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

HRID 1473040Notes

Reaction equation

HRID 1473040 reaction equation
[NH2:1][C:2](=[O:42])[CH2:3][C:4]1[CH:41]=[CH:40][CH:39]=[CH:38][C:5]=1[CH2:6][CH2:7][C:8]1[C:13]([C:14]([F:17])([F:16])[F:15])=[CH:12][N:11]=[C:10]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([CH:25]3[CH2:30][CH2:29][CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26]3)=[CH:21][CH:20]=2)[N:9]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[NH:27]1[CH2:28][CH2:29][CH2:30][CH:25]([C:22]2[CH:23]=[CH:24][C:19]([NH:18][C:10]3[N:9]=[C:8]([CH2:7][CH2:6][C:5]4[CH:38]=[CH:39][CH:40]=[CH:41][C:4]=4[CH2:3][C:2]([NH2:1])=[O:42])[C:13]([C:14]([F:17])([F:15])[F:16])=[CH:12][N:11]=3)=[CH:20][CH:21]=2)[CH2:26]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71229644tert-Butyl 3-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Product 1

HCID 601645862-(2-(2-(2-((4-(Piperidin-3-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 72.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

tert-Butyl 3-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I28) (0.184 g, 0.315 mmol) was dissolved in DCM (10 mL) under an atmosphere of nitrogen. Trifluoroacetic acid (1.21 mL, 15.8 mmol) was added to the solution and the reaction was stirred at room temperature for 1 hour. Volatiles were removed in vacuo, EtOAc (100 mL) and 2 M aq. NaOH (70 mL) were added to the residue and the layers were separated. The aqueous layer was extracted with EtOAc (70 mL), the combined organics were washed with water (50 mL), brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo to give a white solid. The solid was taken up in DCM (˜7 mL) and methanol (˜1 mL) and concentrated in vacuo. The process was repeated with only DCM twice to give the title compound (4) (0.110 g, 72% yield) as a white solid; 1H NMR (400 MHz, d6-DMSO) δ 10.13 (s, 1H), 8.65 (s, 1H), 7.69-7.62 (m, 2H), 7.44 (s, 1H), 7.26-7.12 (m, 6H), 6.93 (s, 1H), 3.50 (s, 2H), 3.15-3.06 (m, 2H), 3.06-2.90 (m, 4H), 2.60-2.43 (m, 3H), 1.85 (d, J=11.1 Hz, 1H), 1.69-1.61 (m, 1H), 1.61-1.41 (m, 2H). 3 Aliphatic protons obscured by residual DMSO. LCMS Method C: rt 4.81 min; m/z 484.3 [M+H]+.

Workup

  1. customVolatiles were removed in vacuo, EtOAc (100 mL) and 2 M aq. NaOH (70 mL)
  2. additionwere added to the residue
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with EtOAc (70 mL)
  5. washthe combined organics were washed with water (50 mL), brine (50 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a white solid
  10. concentrationmethanol (˜1 mL) and concentrated in vacuo

Sources & evidence

ORD record
ord-5c313352ae7e4742a5c93c0cb6647391
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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