2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl → N-(2,4-dimethyl-6-(7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl)pyridin-3-yl)-3,3-dimethylbutanamide

HRID 383719Notes

Reaction equation

HRID 383719 reaction equation
C1(P(C2CCCCC2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]2C=CC=C[C:15]=2[N:20]([CH3:22])[CH3:21])CCCCC1.CC(C)([O-])C.[K+].BrC1[N:41]=[C:40]([CH3:42])[C:39]([NH:43][C:44](=[O:50])[CH2:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[C:38]([CH3:51])[CH:37]=1.[F:52][C:53]([F:65])([F:64])C1C=NC2CCNCC=2C=1>C1(C)C=CC=CC=1>[CH3:42][C:40]1[C:39]([NH:43][C:44](=[O:50])[CH2:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[C:38]([CH3:51])[CH:37]=[C:22]([N:20]2[CH2:15][CH2:14][C:9]3[C:8](=[CH:13][C:12]([C:53]([F:65])([F:64])[F:52])=[CH:11][CH:10]=3)[CH2:21]2)[N:41]=1

Participants

6

Reactant 4

HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 114810975,6,7,8-Tetrahydro-3-(trifluoromethyl)-1,6-naphthyridineHCID 23665647Potassium tert-butoxideHCID 59868778N-(6-bromo-2,4-dimethylpyridin-3-yl)-3,3-dimethylbutanamide

Product 1

HCID 68739807N-(2,4-dimethyl-6-(7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl)pyridin-3-yl)-3,3-dimethylbutanamide

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Bis(dibenzylidineacetone)palladium (4 mg, 0.069 mmol) and (2′-dicyclohexylphosphanyl-biphenyl-2-yl)-dimethylamine (6.5 mg, 0.014 mmol) were added to dry toluene (1 mL purged with argon) and stirred for 15 minutes under argon. Potassium tert-butoxide (34 mg, 0.3 mmol), 1d (50 mg, 0.17 mmol) and 3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine (28 mg, 0.14 mmol) were then added and the reaction mixture was stirred at 80° C. over night. The reaction mixture was then cooled to room temperature, concentrated and purified by biotage (75% ethyl acetate:hexanes) to afford the tittle compound as a solid. 1H NMR (DMSO-d6, 400 MHz) δ 1.03 (s, 9H), 2.09 (s, 3H), 2.15 (s, 2H), 2.21 (s, 3H), 3.03 (t, J=4 Hz, 2H), 3.92 (t, J=4 Hz, 2H), 4.79 (s, 2H), 6.68 (s, 1H), 8.12 (s, 1H), 8.75 (s, 1H), 9.02 (s, 1H).

Workup

  1. stirringthe reaction mixture was stirred at 80° C. over night
  2. concentrationconcentrated
  3. custompurified by biotage (75% ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-ed84a6fb61b14ed4a239fb1d33b508d0
Source dataset
uspto-grants-2013_02
Patent number
US08367684B2

Reaction notes

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