2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl → N-(2,6-dimethyl-4-(3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)phenyl)-3,3-dimethylbutanamide

HRID 1043826Notes

Reaction equation

HRID 1043826 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.CC(C)([O-])C.[K+].Br[C:36]1[CH: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])[C:54]1[CH:55]=[N:56][C:57]2[CH2:58][CH2:59][NH:60][CH2:61][C:62]=2[CH:63]=1>C1(C)C=CC=CC=1>[CH3:42][C:40]1[CH:41]=[C:36]([N:60]2[CH2:59][CH2:58][C:57]3[N:56]=[CH:55][C:54]([C:53]([F:52])([F:64])[F:65])=[CH:63][C:62]=3[CH2:61]2)[CH:37]=[C:38]([CH3:51])[C:39]=1[NH:43][C:44](=[O:50])[CH2:45][C:46]([CH3:49])([CH3:48])[CH3:47]

Participants

6

Reactant 4

HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 114810975,6,7,8-Tetrahydro-3-(trifluoromethyl)-1,6-naphthyridineHCID 23665647Potassium tert-butoxideHCID 59741059N-(4-Bromo-2,6-dimethyl-phenyl)-3,3-dimethyl-butanamide

Product 1

HCID 25182408N-(2,6-dimethyl-4-(3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)phenyl)-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 (7 mg, 0.015 mmol) were added to dry toluene (1 mL purged with argon) and stirred for 15 minutes under argon. Potassium tert-butoxide (36 mg, 0.32 mmol), N-(4-bromo-2,6-dimethylphenyl)-3,3-dimethylbutanamide (52 mg, 0.17 mmol) and 3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine (WO/04069162) (40 mg, 0.15 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 desired compound as a solid. 1H NMR (DMSO-d6, 400 MHz) δ 1.05 (s, 9H), 2.11 (s, 6H), 2.17 (s, 2H), 3.08 (t, J=5.6 Hz, 2H), 3.64 (t, J=5.9 Hz, 2H), 4.48 (s, 2H), 6.76 (s, 2H), 8.08 (s, 1H), 8.75 (s, 1H), 8.90 (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-b24ca035c4f24b04929f08d823a27d29
Source dataset
uspto-grants-2013_10
Patent number
US08563566B2

Reaction notes

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