Reaktion #83491

Reaktionsgleichung

2-methyl-5-fluorobenzoyl chloride

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

triethylamine

→

desired product

Ausbeute 40.7%

N-[4-(5H-Pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylcarbonyl)phenyl]-5-fluoro-2-methylbenzamide

Ausbeute 40.7%

Lösungsmittel

methylene chloride

methylene chloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe cooling bath is removed
2. 2
   workup.ADDITIONan additional 342 mg of 2-methyl-5-fluorobenzoyl chloride in 2 ml of methylene chloride is added
3. 3
   SonstigeThe cooling bath is removed
4. 4
   workup.STIRRINGstirring
5. 5
   workup.WAITcontinued for 18 hours
6. 6
   SonstigeThe volatiles are removed in vacuo to a residue which
7. 7
   workup.DISSOLUTIONis dissolved in 50 ml of methylene chloride
8. 8
   Waschenwashed with 20 ml each of water, 2N citric acid, 1M sodium bicarbonate and brine
9. 9
   TrocknenThe organic layer is dried over Na2SO4
10. 10
    SonstigeThe filtrate is evaporated in vacuo to a residue which
11. 11
    Sonstigeis crystallized from ethyl acetate-hexane

Vorschrift

To a stirred solution of 500 mg of 10,11-dihydro-10-(4-aminobenzoyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine in 3 ml of methylene chloride, cooled to 0° C., under argon, is added 346 μl of triethylamine followed by the addition of 340 mg of 2-methyl-5-fluorobenzoyl chloride in 2 ml of methylene chloride. The cooling bath is removed and stirring continued for 18 hours. After cooling to 0° C., an additional 342 mg of 2-methyl-5-fluorobenzoyl chloride in 2 ml of methylene chloride is added. The cooling bath is removed and stirring continued for 18 hours. The volatiles are removed in vacuo to a residue which is dissolved in 50 ml of methylene chloride and washed with 20 ml each of water, 2N citric acid, 1M sodium bicarbonate and brine. The organic layer is dried over Na2SO4 and passed through a pad of hydrous magnesium silicate. The filtrate is evaporated in vacuo to a residue which is crystallized from ethyl acetate-hexane to give 295 mg of the desired product as a white solid, m.p. 170°-180° C.

Quelle