2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl → N-(6-(6-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-2,4-dimethylpyridin-3-yl)-3,3-dimethylbutanamide

HRID 383706Notes

Reaction equation

HRID 383706 reaction equation
Br[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([NH:9][C:10](=[O:16])[CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[C:4]([CH3:17])[CH:3]=1.[F:18][C:19]1[CH:20]=[C:21]2[C:26](=[CH:27][CH:28]=1)[CH2:25][NH:24][CH2:23][CH2:22]2.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.CC(C)([O-])C.[K+]>C1(C)C=CC=CC=1>[F:18][C:19]1[CH:20]=[C:21]2[C:26](=[CH:27][CH:28]=1)[CH2:25][N:24]([C:2]1[N:7]=[C:6]([CH3:8])[C:5]([NH:9][C:10](=[O:16])[CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[C:4]([CH3:17])[CH:3]=1)[CH2:23][CH2:22]2

Participants

6

Reactant 4

HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 157187246-Fluoro-1,2,3,4-tetrahydroisoquinolineHCID 23665647Potassium tert-butoxideHCID 59868778N-(6-bromo-2,4-dimethylpyridin-3-yl)-3,3-dimethylbutanamide

Product 1

HCID 59868726N-(6-(6-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-2,4-dimethylpyridin-3-yl)-3,3-dimethylbutanamideYield 73.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

In a tube, a mixture of 1d (0.65 g, 2.15 mmol), 6-fluoro-1,2,3,4-tetrahydroisoquinoline (0.348 g, 2.6 mmol) in toluene (15 ml) was degassed by nitrogen flow for 15 minutes. To this mixture was added tris(dichlorobenzylidenacetone)palladium (0) (0.052 g, 0.055 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (0.08 g, 0.2 mmol) and potassium tert-butoxide (0.437 g, 3.9 mmol). The tube was heated under microwave irradiation (Biotage Initiator®) for 6 hour at 100° C. The reaction mixture was cooled to room temperature, washed with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4, concentrated and chromatographed to yield the title compound (0.584 g, 1.58 mmol, 73%). 1H NMR (CDCl3, 400 MHz) δ 1.14 (s, 9H), 2.19 (s, 3H), 2.27 (s, 2H), 2.35 (s, 3H), 2.91 (t, J=6.2 Hz, 2H), 3.82 (t, J=6.2 Hz, 2H), 4.62 (s, 2H), 6.38 (s, 1H), 6.50 (bs, 1H), 6.85-6.92 (m, 2H), 7.09-7.16 (m, 1H).

Workup

  1. customwas degassed by nitrogen flow for 15 minutes
  2. temperatureThe reaction mixture was cooled to room temperature
  3. washwashed with water
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customchromatographed

Sources & evidence

ORD record
ord-f835c84372394fcebd8f266fd8789577
Source dataset
uspto-grants-2013_02
Patent number
US08367684B2

Reaction notes

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