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

HRID 592366Notes

Reaction equation

HRID 592366 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:34]=[CH:33][C:32]([CH:35]4[CH2:40][CH2:39][N:38](C(OC(C)(C)C)=O)[CH2:37][CH2:36]4)=[CH:31][CH:30]=3)[N:19]=2)[CH2:13][CH2:12]1)(=[O:10])[NH2:9]>C(Cl)Cl>[NH:38]1[CH2:39][CH2:40][CH:35]([C:32]2[CH:31]=[CH:30][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:27])([F:26])[F:25])=[CH:22][N:21]=3)=[CH:34][CH:33]=2)[CH2:36][CH2:37]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86712287tert-Butyl 4-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Product 1

HCID 732962871-(2-(2-(2-((4-(Piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamideYield 93.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of TFA (0.65 mL, 8.5 mmol) and tert-butyl 4-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (A6) (0.13 mg, 0.21 mmol) in DCM (20 mL) was stirred for 24 hours at room temperature under nitrogen. The volatiles were removed in vacuo and the residue was taken up in MeOH and loaded onto an SCX cartridge (10 g). The column was eluted with 5 column volumes of MeOH and then 5 column volumes of 5% v/v aqueous ammonia in MeOH to elute the amine product. The ammoniacal filtrate was evaporated under reduced pressure and the resulting solid was dried under high vacuum to give the title compound 2 as a white solid (100 mg, 93%); 1H NMR (400 MHz, d6-DMSO) δ 10.14 (s, 1H), 8.67 (s, 1H), 7.66 (d, J=8.6 Hz, 2H), 7.37-7.27 (m, 3H), 7.25-7.14 (m, 3H), 6.99 (s, 1H), 6.00 (s, 1H), 3.22-3.13 (m, 2H), 3.13-3.06 (m, 2H), 3.01 (d, J=11.9 Hz, 2H), 2.62-2.52 (m, peaks obscured by solvent), 1.67 (d, J=10.7 Hz, 2H), 1.57-1.40 (m, 4H), 0.97 (s, 2H). LCMS-A: rt 4.963 min; m/z 510 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. washThe column was eluted with 5 column volumes of MeOH
  3. wash5 column volumes of 5% v/v aqueous ammonia in MeOH to elute the amine product
  4. customThe ammoniacal filtrate was evaporated under reduced pressure
  5. customthe resulting solid was dried under high vacuum

Sources & evidence

ORD record
ord-e46912bff853468abe6aad8dbd9f9969
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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