6-Fluoro-1,2,3,4-tetrahydroisoquinoline → N-(2-chloro-4-(6-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-6-(trifluoromethyl)phenyl)-3,3-dimethylbutanamide

HRID 2067786Notes

Reaction equation

HRID 2067786 reaction equation
CC(C)([O-])C.[K+].[F:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[CH2:14][NH:13][CH2:12][CH2:11]2.Br[C:19]1[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[C:22]([NH:29][C:30](=[O:36])[CH2:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[C:21]([Cl:37])[CH:20]=1>C1(C)C=CC=CC=1>[Cl:37][C:21]1[CH:20]=[C:19]([N:13]2[CH2:12][CH2:11][C:10]3[C:15](=[CH:16][CH:17]=[C:8]([F:7])[CH:9]=3)[CH2:14]2)[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[C:22]=1[NH:29][C:30](=[O:36])[CH2:31][C:32]([CH3:34])([CH3:33])[CH3:35]

Participants

5

Reactant 3

HCID 157187246-Fluoro-1,2,3,4-tetrahydroisoquinolineHCID 23665647Potassium tert-butoxideHCID 58097337N-(4-bromo-2-chloro-6-(trifluoromethyl)phenyl)-3,3-dimethylbutanamide

Product 1

HCID 24936953N-(2-chloro-4-(6-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-6-(trifluoromethyl)phenyl)-3,3-dimethylbutanamide

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 (122 mg, 1.08 mmol), 6-fluoro-1,2,3,4-tetrahydroisoquinoline (96 mg, 0.65 mmol), and N-(4-bromo-2-chloro-6-(trifluoromethyl)phenyl)-3,3-dimethylbutanamide (200 mg, 0.54 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:methanol 5%) to afford the title compound as a solid. m/z=441 [M−1]−.

Workup

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

Sources & evidence

ORD record
ord-37f5b2c6dddc47cfa51d99e83b4d255f
Source dataset
uspto-grants-2012_10
Patent number
US08293911B2

Reaction notes

Loading…