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

HRID 1473053Notes

Reaction equation

HRID 1473053 reaction equation
[NH2:1][C:2](=[O:42])[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][CH2:32][CH2:31][N:30]3[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])=[CH:25][CH:24]=2)[N:13]=1.[H][H]>CN(C=O)C.[OH-].[OH-].[Pd+2].CCOC(C)=O>[NH2:1][C:2](=[O:42])[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:21])([F:20])[F:19])=[CH:16][N:15]=[C:14]([NH:22][C:23]2[CH:24]=[CH:25][C:26]([CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][N:30]3[C:35]([O:37][C:38]([CH3:39])([CH3:40])[CH3:41])=[O:36])=[CH:27][CH:28]=2)[N:13]=1

Participants

6

Reactant 2

HCID 71229343tert-Butyl 2-(4-((4-((2-(2-amino-2-oxoethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 71229344tert-Butyl 2-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylateYield 74.5%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

tert-Butyl 2-(4-((4-((2-(2-amino-2-oxoethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I40) (0.120 g, 0.207 mmol) was dissolved in dry DMF (5 mL) under an atmosphere of nitrogen. 20% Pearlman's catalyst (0.060 g) in EtOAc (5 mL) was added to the solution and the atmosphere was changed to hydrogen gas (balloon). The reaction was sealed with a balloon and stirred at room temperature for 20 hours at room temperature. The catalyst was removed by filtration through Celite, which was washed with EtOAc (5×10 mL). The solvent was removed in vacuo to give a pale yellow gum which was purified by silica gel chromatography (Biotage, Isolera 12 g Si Cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound (I41) (0.090 g, 74% yield) as a pale yellow solid; 1H NMR (400 MHz, d5-DMSO) δ 10.20 (s, 1H), 8.67 (s, 1H), 7.73 (d, J=8.7 Hz, 2H), 7.43 (s, 1H), 7.26-7.21 (m, 1H), 7.20-7.09 (m, 5H), 6.89 (s, 1H), 5.31-5.19 (m, 1H), 3.92 (d, J=13.2 Hz, 1H), 3.49 (s, 2H), 3.16-2.98 (m, 4H), 2.71 (t, J=11.8 Hz, 1H), 2.29 (d, J=13.2 Hz, 1H), 1.75 (t, J=11.0 Hz, 1H), 1.58-1.50 (m, 2H), 1.46-1.23 (m, 11H). LCMS Method C: rt 6.59 min; m/z 584.3 [M+H]+.

Workup

  1. customThe reaction was sealed with a balloon
  2. customThe catalyst was removed by filtration through Celite, which
  3. washwas washed with EtOAc (5×10 mL)
  4. customThe solvent was removed in vacuo
  5. customto give a pale yellow gum which
  6. customwas purified by silica gel chromatography (Biotage, Isolera 12 g Si Cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-d1356218c9a54b37a334fd84e7b5a29f
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

Loading…