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

HRID 383707

反応式

HRID 383707 の反応式
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]([F:31])([F:30])[C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][CH:29]=1)[CH2:26][NH:25][CH2:24][CH2:23]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>[CH3:8][C:6]1[C:5]([NH:9][C:10](=[O:16])[CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[C:4]([CH3:17])[CH:3]=[C:2]([N:25]2[CH2:24][CH2:23][C:22]3[C:27](=[CH:28][CH:29]=[C:20]([C:19]([F:18])([F:31])[F:30])[CH:21]=3)[CH2:26]2)[N:7]=1

参加物

6

反応物 4

HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 181765196-(Trifluoromethyl)-1,2,3,4-tetrahydroisoquinolineHCID 23665647Potassium tert-butoxideHCID 59868778N-(6-bromo-2,4-dimethylpyridin-3-yl)-3,3-dimethylbutanamide

生成物 1

HCID 59868723N-(2,4-dimethyl-6-(6-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl)pyridin-3-yl)-3,3-dimethylbutanamide収率 63%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

In a tube, a mixture of 1d (0.374 g, 1.25 mmol), 6-trifluoromethyl-1,2,3,4-tetrahydroisoquinoline (0.301 g, 1.5 mmol) in toluene (15 ml) was degassed by nitrogen flow for 15 minutes. To this mixture was added tris(dichlorobenzylidenacetone)palladium (0) (0.037 g, 0.04 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (0.06 g, 0.15 mmol) and potassium tert-butoxide (0.336 g, 3.0 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 (0.326 g, 0.78 mmol, 63%). 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), 6.39 (s, 1H), 6.55 (bs, 1H), 6.98 (d, J=7.2 Hz, 2H), 7.24 (s, 1H).

後処理

  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

出典と根拠

ORDレコード
ord-358469cc890e4cfb9e72d4c27b394a3e
出典データセット
uspto-grants-2013_02
特許番号
US08367684B2

関連ノート

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