Reaktion #1917271

Reaktionsgleichung

triethylamine

2-chloro-2′-fluoro-5-methoxy-[1,1′-biphenyl]-4-carboxylic acid

2-Chloro-2′-fluoro-5-methoxy-[1,1′-biphenyl]-4-carboxylic acid

thionyl chloride

10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine

→

title compound

10-{[6-Chloro-3-methoxy-2′-fluoro-[1,1′-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine

Lösungsmittel

dichloromethane

tetrahydrofuran

N,N-dimethylformamide

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe reaction mixture was stirred for 2 hours
2. 2
   Waschenwashed with saturated aqueous sodium bicarbonate and brine
3. 3
   TrocknenThe organic layer was dried over anhydrous magnesium sulfate
4. 4
   Filtrationfiltered
5. 5
   Sonstigeevaporated to dryness
6. 6
   SonstigeRecrystallization of the residue from ethyl acetate/heptane

Vorschrift

To a stirred solution of 2-chloro-2′-fluoro-5-methoxy-[1,1′-biphenyl]-4-carboxylic acid of Step A (3.80 g, 13.5 mmol) in tetrahydrofuran (20 mL) containing a catalytic amount of N,N-dimethylformamide was added dropwise thionyl chloride (1.77 g, 14.9 mmol). The reaction mixture was stirred for 2 hours, and then added dropwise to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (2.49 g, 13.5 mmol) in tetrahydrofuran (20 mL) containing triethylamine (3.0 g, 29.8 mmol). The reaction mixture was stirred for 2 hours, diluted with dichloromethane and washed with saturated aqueous sodium bicarbonate and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness. Recrystallization of the residue from ethyl acetate/heptane provided the title compound as a pale yellow solid, m.p. 192–194° C., found to be 99.99% pure by analytical HPLC [Primesphere C-18 column (2.0×150 mm); mobile phase: gradient from 10 to 100% of acetonitrile/water containing 0.1% phosphoric acid, 7 minute gradient].

Quelle