1,2,3,4-Tetrahydroisoquinoline → N-(2-chloro-4-(3,4-dihydroisoquinolin-2(1H)-yl)-6-(trifluoromethyl)phenyl)-3-cyclopentyl propanamide

HRID 880659Notes

Reaction equation

HRID 880659 reaction equation
CC(C)([O-])C.[K+].[CH2:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:10][CH2:9][NH:8]1.Br[C:18]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[C:21]([NH:28][C:29](=[O:37])[CH2:30][CH2:31][CH:32]2[CH2:36][CH2:35][CH2:34][CH2:33]2)=[C:20]([Cl:38])[CH:19]=1>C1(C)C=CC=CC=1>[Cl:38][C:20]1[CH:19]=[C:18]([N:8]2[CH2:9][CH2:10][C:11]3[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH2:7]2)[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[C:21]=1[NH:28][C:29](=[O:37])[CH2:30][CH2:31][CH:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

5

Reactant 3

HCID 70461,2,3,4-TetrahydroisoquinolineHCID 23665647Potassium tert-butoxideHCID 58097325N-(4-Bromo-2-chloro-6-trifluoromethyl-phenyl)-3-cyclopentyl propionamide

Product 1

HCID 24936952N-(2-chloro-4-(3,4-dihydroisoquinolin-2(1H)-yl)-6-(trifluoromethyl)phenyl)-3-cyclopentyl propanamideYield 28%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Bis(dibenzylidineacetone)palladium (2 mg, 0.0035 mmol) and (2′-dicyclohexyl phosphanyl-biphenyl-2-yl)-dimethylamine (3.3 mg, 0.0084 mmol) were added to dry toluene (10 mL purged with argon) and stirred for 15 minutes under argon. Potassium tert-butoxide (150 mg, 1.34 mmol), 1,2,3,4-tetrahydroisoquinoline (107 mg, 0.8 mmol), and N-(4-bromo-2-chloro-6-trifluoromethyl phenyl)-3-cyclopentyl propionamide (200 mg, 0.5 mmol) were then added, and the reaction mixture was stirred at 90° C. overnight. The reaction mixture was then cooled to room temperature, concentrated, and purified by thin layer chromatography (dichloromethane:ethanol 5%) to afford the title compound as a solid.

Workup

  1. stirringthe reaction mixture was stirred at 90° C. overnight
  2. concentrationconcentrated
  3. custompurified by thin layer chromatography (dichloromethane:ethanol 5%)

Sources & evidence

ORD record
ord-d8bc8f64ebb3442b93634e4d304862c9
Source dataset
uspto-grants-2015_03
Patent number
US08993593B2

Reaction notes

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