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

HRID 592360Notes

Reaction equation

HRID 592360 reaction equation
[NH2:1][C:2](=[O:44])[CH:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]#[C:13][C:14]1[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][N:17]=[C:16]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([CH:31]3[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH2:32]3)=[CH:27][CH:26]=2)[N:15]=1)[CH2:4][CH3:5].CCN(CC)CC>CN(C=O)C.CCOC(C)=O.[Pd]>[NH2:1][C:2](=[O:44])[CH:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:12][CH2:13][C:14]1[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][N:17]=[C:16]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([CH:31]3[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH2:32]3)=[CH:27][CH:26]=2)[N:15]=1)[CH2:4][CH3:5]

Participants

6

Reactant 2

HCID 8471TriethylamineHCID 86712282tert-Butyl 4-(4-((4-((2-(1-amino-1-oxobutan-2-yl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Product 1

HCID 86712283tert-Butyl 4-(4-((4-(2-(1-amino-1-oxobutan-2-yl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylateYield 244.9%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 10% Pd/C (100 mg), tert-butyl 4-(4-((4-((2-(1-amino-1-oxobutan-2-yl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (A1) (167 mg, 0.275 mmol) and Et3N (1.0 mL) in DMF (10 mL) was stirred under an atmosphere of hydrogen for 16 hours. The resulting mixture was diluted with EtOAc (60 mL), filtered through Celite then the solvent removed under reduced pressure to give the title compound A2 as a yellow oil (412 mg, 98%); 1H NMR (400 MHz, d6-DMSO) δ 10.15 (s, 1H), 8.67 (s, 1H), 7.67 (d, J=8.6 Hz, 2H), 7.49-7.42 (m, 1H), 7.31 (s, 1H), 7.22-7.14 (m, 5H), 6.87 (s, 1H), 4.06 (d, J=10.5 Hz, 2H), 3.61 (dd, J=8.8, 6.1 Hz, 1H), 3.29-2.94 (m, 4H), 2.88-2.74 (m, obscured by solvent), 2.70-2.59 (m, 1H), 2.04-1.92 (m, 1H), 1.74 (d, J=12.6 Hz, 2H), 1.61-1.43 (m, 3H), 1.41 (s, 9H), 0.83 (t, J=7.3 Hz, 3H). LCMS-A: rt 6.722 min; m/z 612 [M+H]+.

Workup

  1. filtrationfiltered through Celite
  2. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-1c20a54e7b404d848242abb06e1b7220
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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