tert-Butyl 4-(4-((4-((2-(2-amino-2-oxoethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-(trifluoromethoxy)phenyl)piperidine-1-carboxylate → tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-(trifluoromethoxy)phenyl)piperidine-1-carboxylate

HRID 2272437Notes

Reaction equation

HRID 2272437 reaction equation
[NH2:1][C:2](=[O:47])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]#[C:11][C:12]1[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][N:15]=[C:14]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([CH:29]3[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]3)=[CH:25][C:24]=2[O:42][C:43]([F:46])([F:45])[F:44])[N:13]=1>CN(C=O)C.CCOC(C)=O.[OH-].[OH-].[Pd+2]>[NH2:1][C:2](=[O:47])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][CH2:11][C:12]1[C:17]([C:18]([F:19])([F:21])[F:20])=[CH:16][N:15]=[C:14]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([CH:29]3[CH2:30][CH2:31][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:33][CH2:34]3)=[CH:25][C:24]=2[O:42][C:43]([F:46])([F:45])[F:44])[N:13]=1

Participants

5

Reactant 1

HCID 86675846tert-Butyl 4-(4-((4-((2-(2-amino-2-oxoethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-(trifluoromethoxy)phenyl)piperidine-1-carboxylate

Product 1

HCID 86675847tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-(trifluoromethoxy)phenyl)piperidine-1-carboxylateYield 88%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

tert-Butyl 4-(4-((4-((2-(2-amino-2-oxoethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-(trifluoromethoxy)phenyl)piperidine-1-carboxylate (I49) (72.0 mg, 0.108 mmol) was dissolved in dry DMF (7 mL) under an atmosphere of nitrogen, and a slurry of 10% Pd(OH)2/C (0.050 g) in EtOAc (2 mL) was added. The mixture then was stirred vigorously under hydrogen for 24 hours. Upon completion, the reaction was filtered through a pad of celite, which was washed with EtOAc (40 mL). The combined filtrates were concentrated in vacuo to give a pale yellow oil. The crude product was purified by silica gel chromatography (12 g Si Cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound (I50) (0.064 g, 88% yield) as an off-white solid; 1H NMR (400 MHz, d6-DMSO) δ 9.80 (s, 1H), 8.60 (s, 1H), 7.61 (d, J=8.1 Hz, 1H), 7.39 (s, 1H), 7.32-7.26 (m, 2H), 7.21 (dt, J=6.7, 3.4 Hz, 1H), 7.18-7.08 (m, 3H), 6.90 (s, 1H), 4.09 (d, J=12.1 Hz, 2H), 3.45 (s, 2H), 3.09-2.94 (m, 4H), 2.88-2.72 (m, 3H) 1.79 (d, J=12.3 Hz, 2H), 1.59-1.38 (m, 11H). LCMS Method C: rt 6.75 min, m/z 668.1 [M+H]+.

Workup

  1. filtrationUpon completion, the reaction was filtered through a pad of celite, which
  2. washwas washed with EtOAc (40 mL)
  3. concentrationThe combined filtrates were concentrated in vacuo
  4. customto give a pale yellow oil
  5. customThe crude product was purified by silica gel chromatography (12 g Si Cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-78ed473433eb4679aa9fd286ebd222ec
Source dataset
uspto-grants-2015_09
Patent number
US09120761B2

Reaction notes

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