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

HRID 592476Notes

Reaction equation

HRID 592476 reaction equation
[NH2:1][C:2](=[O:43])[CH:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]#[C:12][C:13]1[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][N:16]=[C:15]([NH:23][C:24]2[CH:25]=[CH:26][C:27]([CH:30]3[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]3)=[N:28][CH:29]=2)[N:14]=1)[CH3:4]>CN(C=O)C.CCN(CC)CC.[Pd]>[NH2:1][C:2](=[O:43])[CH:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH2:11][CH2:12][C:13]1[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][N:16]=[C:15]([NH:23][C:24]2[CH:25]=[CH:26][C:27]([CH:30]3[CH2:31][CH2:32][N:33]([C:36]([O:38][C:39]([CH3:41])([CH3:42])[CH3:40])=[O:37])[CH2:34][CH2:35]3)=[N:28][CH:29]=2)[N:14]=1)[CH3:4]

Participants

5

Reactant 1

HCID 86712342tert-Butyl 4-(5-((4-((2-(1-amino-1-oxopropan-2-yl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

Product 1

HCID 86712343tert-Butyl 4-(5-((4-(2-(1-amino-1-oxopropan-2-yl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of tert-Butyl 4-(5-((4-((2-(1-amino-1-oxopropan-2-yl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate A71 (0.139 g, 0.234 mmol) and 10% Pd/C (0.156 g) in DMF (3.0 mL) and Et3N (0.30 mL) was stirred under a hydrogen atmosphere for 112 hours. The mixture was filtered through Celite and concentrated under reduced pressure before being purified using silica gel column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C., 0-20% MeOH in EtOAc) to give the title compound A72 (0.060 g, 42%). LCMS-D: rt 3.568 min; m/z 599.4 [M+H]+.

Workup

  1. filtrationThe mixture was filtered through Celite
  2. concentrationconcentrated under reduced pressure
  3. custombefore being purified
  4. customsilica gel column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C., 0-20% MeOH in EtOAc)

Sources & evidence

ORD record
ord-e1aaa103747a461bb1f6c29786830520
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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