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

HRID 592361Notes

Reaction equation

HRID 592361 reaction equation
C(O)(C(F)(F)F)=O.[NH2:8][C:9](=[O:51])[CH:10]([C:13]1[CH:50]=[CH:49][CH:48]=[CH:47][C:14]=1[CH2:15][CH2:16][C:17]1[C:22]([C:23]([F:26])([F:25])[F:24])=[CH:21][N:20]=[C:19]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([CH:34]3[CH2:39][CH2:38][N:37](C(OC(C)(C)C)=O)[CH2:36][CH2:35]3)=[CH:30][CH:29]=2)[N:18]=1)[CH2:11][CH3:12]>C(Cl)Cl>[NH:37]1[CH2:38][CH2:39][CH:34]([C:31]2[CH:30]=[CH:29][C:28]([NH:27][C:19]3[N:18]=[C:17]([CH2:16][CH2:15][C:14]4[CH:47]=[CH:48][CH:49]=[CH:50][C:13]=4[CH:10]([CH2:11][CH3:12])[C:9]([NH2:8])=[O:51])[C:22]([C:23]([F:26])([F:25])[F:24])=[CH:21][N:20]=3)=[CH:33][CH:32]=2)[CH2:35][CH2:36]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86712283tert-Butyl 4-(4-((4-(2-(1-amino-1-oxobutan-2-yl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Product 1

HCID 732962862-(2-(2-(2-((4-(Piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)butanamideYield 71.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of TFA (0.84 mL, 11 mmol) and tert-butyl 4-(4-((4-(2-(1-amino-1-oxobutan-2-yl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (A2) (168 mg, 0.275 mmol) in DCM (20 mL) was stirred for 24 hours at room temperature under a nitrogen atmosphere. 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 residue was taken up in DCM (˜2 mL). Cyclohexane (˜10 mL) was added and the resulting suspension sonicated for 10 minutes. The precipitate was isolated by filtration to give the title compound 1 as an off-white solid (100 mg, 71%); 1H NMR (400 MHz, d6-DMSO) δ 10.14 (s, 1H), 8.67 (s, 1H), 7.66 (d, J=8.6 Hz, 2H), 7.51-7.43 (m, 1H), 7.31 (s, 1H), 7.22-7.10 (m, 5H), 6.87 (s, 1H), 3.61 (dd, J=8.8, 6.1 Hz, 1H), 3.22-2.89 (m, 6H), 2.62-2.53 (m, 3H), 2.07-1.91 (m, 1H), 1.67 (d, J=12.0 Hz, 2H), 1.62-1.42 (m, 3H), 0.87-0.80 (m, 3H). LCMS-A: rt 4.973 min; m/z 512 [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. additionCyclohexane (˜10 mL) was added
  6. customthe resulting suspension sonicated for 10 minutes
  7. customThe precipitate was isolated by filtration

Sources & evidence

ORD record
ord-bef658a8010f40939d7c37c15dcf60a3
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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