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

HRID 1473073Notes

Reaction equation

HRID 1473073 reaction equation
[CH3:1][NH:2][C:3](=[O:43])[CH2:4][C:5]1[CH:42]=[CH:41][CH:40]=[CH:39][C:6]=1[CH2:7][CH2:8][C:9]1[C:14]([C:15]([F:18])([F:17])[F:16])=[CH:13][N:12]=[C:11]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([N:26]3[CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28][CH2:27]3)=[CH:22][CH:21]=2)[N:10]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[CH3:1][NH:2][C:3](=[O:43])[CH2:4][C:5]1[CH:42]=[CH:41][CH:40]=[CH:39][C:6]=1[CH2:7][CH2:8][C:9]1[C:14]([C:15]([F:18])([F:16])[F:17])=[CH:13][N:12]=[C:11]([NH:19][C:20]2[CH:21]=[CH:22][C:23]([N:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)=[CH:24][CH:25]=2)[N:10]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86675718tert-Butyl 4-(4-((4-(2-(2-(methylamino)-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate

Product 1

HCID 60164697N-Methyl-2-(2-(2-(2-((4-(piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

tert-Butyl 4-(4-((4-(2-(2-(methylamino)-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate (I56) (0.087 g, 0.15 mmol) was dissolved in DCM (5 mL) under an atmosphere of nitrogen. Trifluoroacetic acid (0.222 mL, 2.906 mmol) was added to the solution and the reaction was stirred at room temperature for 6 hours. Volatiles were removed in vacuo, EtOAc (70 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 (2×70 mL), the combined organics were washed with water (50 mL), brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo to give a solid which was taken up in DCM (˜10 mL) and methanol (˜1 mL) and concentrated in vacuo. The process was repeated with only DCM twice after which the sample was further dried on high-vacuum to give the title compound (I4) (0.068 g, 94% yield) as a pale yellow solid; 1H NMR (400 MHz, d6-DMSO) δ 9.97 (s, 1H), 8.60 (s, 1H), 7.93-7.85 (m, 1H), 7.60-7.53 (m, 2H), 7.23-7.12 (m, 4H), 6.91-6.86 (m, 2H), 3.50 (s, 2H), 3.14-3.06 (m, 2H), 3.02-2.93 (m, 6H), 2.87-2.80 (m, 4H), 2.56 (d, J=4.6 Hz, 3H). LCMS Method A: rt 4.37 min; m/z 499.6 [M+H]+.

Workup

  1. customVolatiles were removed in vacuo, EtOAc (70 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 (2×70 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 solid which
  10. concentrationmethanol (˜1 mL) and concentrated in vacuo
  11. customwas further dried on high-vacuum

Sources & evidence

ORD record
ord-ea8d12033da840888a1ec98664aa8b53
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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