Trifluoroacetic acid → 1-(2-(2-(2-((6-(Piperidin-4-yl)pyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

HRID 592375Notes

Reaction equation

HRID 592375 reaction equation
C(O)(C(F)(F)F)=O.[C:8]([C:11]1([C:14]2[CH:51]=[CH:50][CH:49]=[CH:48][C:15]=2[CH2:16][CH2:17][C:18]2[C:23]([C:24]([F:27])([F:26])[F:25])=[CH:22][N:21]=[C:20]([NH:28][C:29]3[CH:30]=[CH:31][C:32]([CH:35]4[CH2:40][CH2:39][N:38](C(OC(C)(C)C)=O)[CH2:37][CH2:36]4)=[N:33][CH:34]=3)[N:19]=2)[CH2:13][CH2:12]1)(=[O:10])[NH2:9]>C(Cl)Cl>[NH:38]1[CH2:37][CH2:36][CH:35]([C:32]2[N:33]=[CH:34][C:29]([NH:28][C:20]3[N:19]=[C:18]([CH2:17][CH2:16][C:15]4[CH:48]=[CH:49][CH:50]=[CH:51][C:14]=4[C:11]4([C:8]([NH2:9])=[O:10])[CH2:12][CH2:13]4)[C:23]([C:24]([F:26])([F:25])[F:27])=[CH:22][N:21]=3)=[CH:30][CH:31]=2)[CH2:40][CH2:39]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86712293tert-Butyl 4-(5-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

Product 1

HCID 732964281-(2-(2-(2-((6-(Piperidin-4-yl)pyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamideYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of TFA (0.386 mL, 5.04 mmol) and tert-butyl 4-(5-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate (A12) (0.077 g, 0.13 mmol) in DCM (10.0 mL) was stirred at room temperature for 3.5 h under N2. The volatiles were removed in vacuo and the residue was dissolved in DCM (˜1 mL). Cyclohexane (˜5 mL) was added until a white precipitate formed. The resulting suspension was sonicated for 10 minutes and the solid was isolated by filtration and dried to give the title compound 5 as an off-white solid (0.042 g, 65%); 1H NMR (400 MHz, d6-DMSO) δ 10.31 (s, 1H), 8.75 (d, J=2.4 Hz, 1H), 8.72 (s, 1H), 8.13 (d, J=7.3 Hz, 1H), 7.39-7.18 (m, 5H), 6.98 (s, 1H), 6.02 (s, 1H), 3.19-3.05 (m, 6H), 2.81-2.59 (m, 3H), 1.79 (d, J=11.0 Hz, 2H), 1.63 (qd, J=12.5, 3.8 Hz, 2H), 1.47-1.41 (m, 2H), 1.02-0.92 (m, 2H). LCMS-A: rt 4.445 min; m/z 511 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. dissolutionthe residue was dissolved in DCM (˜1 mL)
  3. additionCyclohexane (˜5 mL) was added until a white precipitate
  4. customformed
  5. customThe resulting suspension was sonicated for 10 minutes
  6. customthe solid was isolated by filtration
  7. customdried

Sources & evidence

ORD record
ord-9b526b92db40426fabec65e49a2decc8
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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