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

HRID 1473124Notes

Reaction equation

HRID 1473124 reaction equation
[NH2:1][C:2](=[O:42])[CH2:3][C:4]1[C:5]([CH2:10][CH2:11][C:12]2[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][N:15]=[C:14]([NH:22][C:23]3[CH:28]=[CH:27][C:26]([CH:29]4[CH2:34][CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31][CH2:30]4)=[CH:25][CH:24]=3)[N:13]=2)=[N:6][CH:7]=[CH:8][N:9]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:32]1[CH2:31][CH2:30][CH:29]([C:26]2[CH:27]=[CH:28][C:23]([NH:22][C:14]3[N:13]=[C:12]([CH2:11][CH2:10][C:5]4[C:4]([CH2:3][C:2]([NH2:1])=[O:42])=[N:9][CH:8]=[CH:7][N:6]=4)[C:17]([C:18]([F:20])([F:19])[F:21])=[CH:16][N:15]=3)=[CH:24][CH:25]=2)[CH2:34][CH2:33]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71229661tert-Butyl 4-(4-((4-(2-(3-(2-amino-2-oxoethyl)pyrazin-2-yl)ethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Product 1

HCID 682824942-(3-(2-(2-((4-(Piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)pyrazin-2-yl)acetamideYield 88%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 4-(4-((4-(2-(3-(2-amino-2-oxoethyl)pyrazin-2-yl)ethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I104) (66 mg, 0.11 mmol), DCM (20 mL) and TFA (2 mL) were stirred at room temperature for 17 hours, then concentrated. The residue was suspended in 10% NaOH (10 mL) and brine (10 mL), and the mixture extracted with ethyl acetate (4×20 mL). The combined ethyl acetate phases were washed with brine, dried (sodium sulphate) and evaporated to give the title compound (26) (47 mg, 85% yield) as a yellow solid; 1H NMR (400 MHz, d6-DMSO) δ 10.05 (s, 1H), 8.64 (s, 1H), 8.42 (d, J=2.5 Hz, 1H), 8.39 (d, J=2.5 Hz, 1H), 7.61 (s, 1H), 7.54 (d, J=6.7 Hz, 2H), 7.14 (d, J=8.4 Hz, 2H), 7.08 (s, 1H), 3.78 (s, 2H), 3.07-2.97 (m, 2H), 2.63-2.53 (m, overlaps with solvent), 1.67 (d, J=12.1 Hz, 2H), 1.55-1.43 (m, 2H), 1.23 (s, 1H). LCMS Method C: rt 4.36 min; m/z 486.1 [M+H]+; m/z 484.1 [M−H]−.

Workup

  1. concentrationconcentrated
  2. extractionbrine (10 mL), and the mixture extracted with ethyl acetate (4×20 mL)
  3. washThe combined ethyl acetate phases were washed with brine
  4. dry with materialdried (sodium sulphate)
  5. customevaporated

Sources & evidence

ORD record
ord-1915a47f74c143c6bfadb4a154ae5bc6
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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