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

HRID 705766Notes

Reaction equation

HRID 705766 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]([CH:25]3[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH2:26]3)=[CH:21][C:20]=2[CH2:38][CH3:39])[N:9]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:38]([C:20]1[CH:21]=[C:22]([CH:25]2[CH2:26][CH2:27][NH:28][CH2:29][CH2:30]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:17])([F:16])[F:15])=[CH:12][N:11]=1)[CH3:39]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71232246tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-ethylphenyl)piperidine-1-carboxylate

Product 1

HCID 601622462-(2-(2-(2-((2-Ethyl-4-(piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamideYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-ethylphenyl)piperidine-1-carboxylate, (I44) (120 mg, 0.20 mmol) was dissolved in DCM (20 mL), TFA (2 mL) was added and the mixture stirred for 16 hours at room temperature. The mixture was concentrated and the residue suspended in 10% sodium hydroxide (10 mL) and brine (10 mL). The mixture was extracted with ethyl acetate (4×20 mL), the combined extracts washed with brine, dried (sodium sulphate) evaporated and the residue evaporated for ether to give the title compound (8) (93 mg, 93% yield) as a white solid; 1H NMR (400 MHz, d6-DMSO) δ 9.47 (s, 1H), 8.49 (s, 1H), 7.37 (s, 1H), 7.26-7.18 (m, 2H), 7.17-7.09 (m, 4H), 7.05 (dd, J=8.2, 1.9 Hz, 1H), 6.89 (s, 1H), 3.44 (s, 2H), 3.09-2.88 (m, 6H), 2.62-2.54 (m, overlaps with DMSO), 1.70 (d, J=11.4 Hz, 2H), 1.52 (qd, J=12.3, 3.7 Hz, 2H), 1.10 (t, J=7.5 Hz, 3H), LCMS Method C: 4.96 min; m/z 512.2 [M+H]+, 534.2 [M+Na]+; m/z 510.2 [M−H]−.

Workup

  1. concentrationThe mixture was concentrated
  2. extractionThe mixture was extracted with ethyl acetate (4×20 mL)
  3. washthe combined extracts washed with brine
  4. dry with materialdried (sodium sulphate)
  5. customevaporated
  6. customthe residue evaporated for ether

Sources & evidence

ORD record
ord-4c5e3e7e28294fd1909ea3fdce08b494
Source dataset
uspto-grants-2015_11
Patent number
US09174946B2

Reaction notes

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