Trifluoroacetic acid → 2-(2-(2-((1-(piperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-(trifluoromethyl)pyrimidin-4-ylethyl)phenyl)propanamide

HRID 592466Notes

Reaction equation

HRID 592466 reaction equation
[NH2:1][C:2](=[O:42])[CH:3]([C:5]1[CH:41]=[CH:40][CH:39]=[CH:38][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:21]=[N:22][N:23]([CH:25]3[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH2:26]3)[CH:24]=2)[N:10]=1)[CH3:4].C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+].[OH-].[Na+]>C(Cl)Cl>[NH:28]1[CH2:27][CH2:26][CH:25]([N:23]2[CH:24]=[C:20]([NH:19][C:11]3[N:10]=[C:9]([CH2:8][CH2:7][C:6]4[CH:38]=[CH:39][CH:40]=[CH:41][C:5]=4[CH:3]([CH3:4])[C:2]([NH2:1])=[O:42])[C:14]([C:15]([F:16])([F:18])[F:17])=[CH:13][N:12]=3)[CH:21]=[N:22]2)[CH2:30][CH2:29]1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acid2×HCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 86712339tert-Butyl 4-(4-((4-(2-(1-amino-1-oxopropan-2-yl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Product 1

HCID 732951232-(2-(2-((1-(piperidin-4-yl)-1H-pyrazol-4-yl)amino)-5-(trifluoromethyl)pyrimidin-4-ylethyl)phenyl)propanamideYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of tert-butyl 4-(4-((4-(2-(1-amino-1-oxopropan-2-yl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)piperidine-1-carboxylate A66 (3.41 g, 5.80 mmol) in DCM (50 mL) was cooled to 0° C. and treated with TFA (4.44 mL, 0.058 mol). The mixture was stirred at 0° C. for 1 hour and then at room temperature for 3 hours. An extra aliquot of TFA (2.2 mL, 0.029 mol) was added to the mixture and stirring was continued for 2 hours at room temperature. Sat. aq. NaHCO3 (˜50 mL) was carefully added, followed by aq. NaOH (2 M, ˜50 mL). DCM was removed in vacuo and the resultant aqueous mixture was diluted with H2O (˜50 mL). The white suspension was sonicated for 10 minutes and vacuum filtered. The isolated solid was washed with water and air dried to give the title compound 56 as a white solid (2.8 g, 99%). 1H NMR (400 MHz, d6-DMSO) δ 10.20-10.08 (m, 1H), 8.69-8.56 (m, 1H), 8.02-7.93 (m, 1H), 7.58 (s, 1H), 7.44-7.35 (m, 1H), 7.27-7.14 (m, 4H), 6.92-6.80 (m, 1H), 4.21-4.08 (m, 1H), 3.91-3.79 (m, 1H), 3.18-2.91 (m, 6H), 2.61-2.50 (m, 2H), 1.92-1.86 (m, 2H), 1.81-1.68 (m, 2H), 1.33 (d, J=6.9 Hz, 3H). LCMS-A: rt 4.79 min; m/z 488 [M+H]+.

Workup

  1. waitat room temperature for 3 hours
  2. stirringstirring
  3. waitwas continued for 2 hours at room temperature
  4. customDCM was removed in vacuo
  5. additionthe resultant aqueous mixture was diluted with H2O (˜50 mL)
  6. customThe white suspension was sonicated for 10 minutes
  7. filtrationvacuum filtered
  8. washThe isolated solid was washed with water and air
  9. customdried

Sources & evidence

ORD record
ord-e73f66a174744f11886c537d0ec20f56
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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