Potassium Phosphate, Tribasic → 7,8-Dimethoxy-[10,11-dihydro-5H-pyrrolo [2,1-c][1,4]benzodiazepin-10-yl][2-methyl-2'-(trifluoromethyl)[1,1'-biphenyl]-4-yl]methanone

HRID 1830084Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1830084
[CH3:1][O:2][C:3]1[C:4]([O:27][CH3:28])=[CH:5][C:6]2[N:12]([C:13]([C:15]3[CH:20]=[CH:19][C:18](Br)=[C:17]([CH3:22])[CH:16]=3)=[O:14])[CH2:11][C:10]3=[CH:23][CH:24]=[CH:25][N:9]3[CH2:8][C:7]=2[CH:26]=1.[F:29][C:30]([F:41])([F:40])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O1CCOCC1>[CH3:1][O:2][C:3]1[C:4]([O:27][CH3:28])=[CH:5][C:6]2[N:12]([C:13]([C:15]3[CH:20]=[CH:19][C:18]([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=4[C:30]([F:41])([F:40])[F:29])=[C:17]([CH3:22])[CH:16]=3)=[O:14])[CH2:11][C:10]3=[CH:23][CH:24]=[CH:25][N:9]3[CH2:8][C:7]=2[CH:26]=1

Komponenten

6

Edukt 3

HCID 62657Potassium Phosphate, TribasicHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 219477397,8-dimethoxy-(10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-(4-bromo-3-methyl-phenyl)-methanone

Produkt 1

HCID 219477487,8-Dimethoxy-[10,11-dihydro-5H-pyrrolo [2,1-c][1,4]benzodiazepin-10-yl][2-methyl-2'-(trifluoromethyl)[1,1'-biphenyl]-4-yl]methanoneAusbeute 87,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

The 7,8-dimethoxy-(10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-(4-bromo-3-methyl-phenyl)-methanone of Step C (1.0 g) was reacted with 2-trifluoromethylphenyl boronic acid (0.645 g, 1.5 equiv.), potassium phosphate (0.964 g, 2.0 equiv.) and a catalytic amount (0.050 g) of tetrakis(triphenylphosphine) palladium(0) in refluxing dioxane (10 mL) under nitrogen for 24 hours. The reaction was then cooled to room temperature, filtered through Celite, and the solvent removed in vacuo. The residue was dissolved in dichloromethane and the solution was washed with water, dried over anhydrous magnesium sulfate, filtered and evaporated to dryness. The crude product so obtained was purified by chromatography on silica gel eluting with 5% ethyl acetate/dichloromethane to provide the title product (1.0 g) as a white crystalline solid, m.p. 187–188° C.

Aufarbeitung

  1. filtrationfiltered through Celite
  2. customthe solvent removed in vacuo
  3. dissolutionThe residue was dissolved in dichloromethane
  4. washthe solution was washed with water
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe crude product so obtained
  9. customwas purified by chromatography on silica gel eluting with 5% ethyl acetate/dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-94774aded0574596996b96e6d2fb6c56
Quelldatensatz
uspto-grants-2006_06
Patentnummer
US07064120B2

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