Potassium tert-butoxide → N-[2-Chloro-4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-6-trifluoromethyl-phenyl]-3-cyclopentyl propionamide

HRID 880665Notes

Reaction equation

HRID 880665 reaction equation
CC(C)([O-])C.[K+].Cl.[F:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH2:15][NH:14][CH2:13][CH2:12]2.Br[C:20]1[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[C:23]([NH:30][C:31](=[O:39])[CH2:32][CH2:33][CH:34]2[CH2:38][CH2:37][CH2:36][CH2:35]2)=[C:22]([Cl:40])[CH:21]=1>C1(C)C=CC=CC=1>[Cl:40][C:22]1[CH:21]=[C:20]([N:14]2[CH2:13][CH2:12][C:11]3[C:16](=[CH:17][CH:18]=[C:9]([F:8])[CH:10]=3)[CH2:15]2)[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[C:23]=1[NH:30][C:31](=[O:39])[CH2:32][CH2:33][CH:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1

Participants

5

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 450740426-Fluoro-1,2,3,4-tetrahydroisoquinoline hydrochlorideHCID 58097325N-(4-Bromo-2-chloro-6-trifluoromethyl-phenyl)-3-cyclopentyl propionamide

Product 1

HCID 24937077N-[2-Chloro-4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-6-trifluoromethyl-phenyl]-3-cyclopentyl propionamide

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 (140 mg, 1.25 mmol), 6-fluoro-1,2,3,4-tetrahydroisoquinoline hydrochloride salt (150 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:methanol 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:methanol 5%)

Sources & evidence

ORD record
ord-be25831e989e4c23b73a79ac9a66f119
Source dataset
uspto-grants-2015_03
Patent number
US08993593B2

Reaction notes

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