Trifluoroacetic acid → 2-(2-(2-(2-((4-(Piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

HRID 1473021Notes

Reaction equation

HRID 1473021 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]([N:25]3[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH2:26]3)=[CH:21][CH:20]=2)[N:9]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[N:25]1([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:16])([F:15])[F:17])=[CH:12][N:11]=3)=[CH:20][CH:21]=2)[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71229345tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate

Product 1

HCID 601644802-(2-(2-(2-((4-(Piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate (I8) (0.131 g, 0.224 mmol) was dissolved in DCM (7 mL) under an atmosphere of nitrogen. Trifluoroacetic acid (0.857 mL, 11.2 mmol) was added to the solution and the reaction was stirred at room temperature for 24 hours. Volatiles were removed in vacuo, EtOAc (70 mL) and 2 M aq. NaOH (70 mL) were added to the oil and the layers were separated. The aqueous layer was extracted with EtOAc (50 mL), the combined organics were washed with brine (50 mL), dried (Na2SO4), filtered and concentrated in vacuo. The resulting solid was taken up in DCM (˜5 mL) and methanol (˜1 mL) and concentrated in vacuo. The process was repeated with only DCM twice to give the title compound (1) (0.104 g, 96% yield) as a pale yellow solid; 1H NMR (400 MHz, d6-DMSO) δ 9.96 (s, 1H), 8.60 (s, 1H), 7.61-7.53 (m, 2H), 7.43 (br s, 1H), 7.25-7.13 (m, 4H), 6.98-6.86 (m, 3H), 3.50 (s, 2H), 3.12-3.05 (m, 2H), 3.04-2.94 (m, 6H), 2.86-2.78 (m, 4H). LCMS Method C: rt 4.774 min; m/z 485.2 [M+H]+.

Workup

  1. customVolatiles were removed in vacuo, EtOAc (70 mL) and 2 M aq. NaOH (70 mL)
  2. additionwere added to the oil
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with EtOAc (50 mL)
  5. washthe combined organics were washed with brine (50 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. concentrationmethanol (˜1 mL) and concentrated in vacuo

Sources & evidence

ORD record
ord-186201a6efc84704b7b1bb1f41681757
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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