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

HRID 705728Notes

Reaction equation

HRID 705728 reaction equation
[NH2:1][C:2](=[O:44])[CH2:3][C:4]1[CH:43]=[CH:42][CH:41]=[CH:40][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][C:20]=2[O:38][CH3:39])[N:9]=1.FC(F)(F)C(O)=O>ClCCl.C(Cl)(Cl)Cl.CC(O)C.[OH-].[Na+]>[CH3:39][O:38][C:20]1[CH:21]=[C:22]([N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[CH:23]=[CH:24][C:19]=1[NH:18][C:10]1[N:9]=[C:8]([CH2:7][CH2:6][C:5]2[CH:40]=[CH:41][CH:42]=[CH:43][C:4]=2[CH2:3][C:2]([NH2:1])=[O:44])[C:13]([C:14]([F:16])([F:17])[F:15])=[CH:12][N:11]=1

Participants

6

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71225669Tert-butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazine-1-carboxylate

Product 1

HCID 601485632-(2-(2-(2-((2-Methoxy-4-(piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 99.1%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 14798Sodium HydroxideSolventHCID 21906603Chloroform isopropyl alcoholSolvent

Procedure

To a solution of tert-butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazine-1-carboxylate (I8) (0.276 g, 0.449 mmol) in dichloromethane (8 mL), was added trifluoroacetic acid (0.669 mL, 8.98 mmol) and the resulting mixture was stirred under a nitrogen atmosphere for 18 hours. The solvents were evaporated in vacuo to give a yellow residue which was dissolved in 3:1 chloroform/2-propanol and 1 M aqueous sodium hydroxide solution. The aqueous layer was extracted with 3:1 chloroform/2-propanol (3×15 mL) and the combined organic extracts were washed with water, brine, dried (magnesium sulfate), filtered and evaporated to give the title compound (1) (0.229 g, 99%) as a yellow foam; 1H NMR (300 MHz, d6-DMSO) δ 2.87-3.10 (m, 12H), 3.46 (s, 2H), 3.78 (s, 3H), 4.32 (d, 1H, J=4.2 Hz), 6.48 (dd, 1H, J=2.2, 8.7 Hz), 6.61 (d, 1H, J=2.1 Hz), 6.88 (brs, 1H), 7.15-7.30 (m, 4H), 7.38 (brs, 1H), 7.46 (brs, 1H), 8.51 (s, 1H) and 8.81 (s, 1H). LCMS Method B: rt 5.65 min; m/z 515.4 [M+H]+.

Workup

  1. customThe solvents were evaporated in vacuo
  2. customto give a yellow residue which
  3. extractionThe aqueous layer was extracted with 3:1 chloroform/2-propanol (3×15 mL)
  4. washthe combined organic extracts were washed with water, brine
  5. dry with materialdried (magnesium sulfate)
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-cb677e4be5d247939fe3f2e1f0a50901
Source dataset
uspto-grants-2015_11
Patent number
US09174946B2

Reaction notes

Loading…