Reaktion #62586

Reaktionsgleichung

2-(5-chloro-7-aminoindolin-1-yl)benzamide

→

4-Chloro-1,2-dihydrobenzo[c]pyrrolo[1,2,3-ef][1,5]benzodiazepin-7-one

Lösungsmittel

methanol dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONSilica gel (510 gm) was added
2. 2
   Sonstigeto absorb the starting material
3. 3
   Sonstigethe solvent was removed as much as possible under vacuum (50° C., 25 mmHg pressure for 1 hr.) The reaction mixture
4. 4
   Temperaturwas then heated at 145°-155° C.
5. 5
   Wascheneluted with DCM (16 l) and 2% CH3OH in DCM (10 l)
6. 6
   workup.ADDITIONThe fractions containing the desired product
7. 7
   Einengenconcentrated
8. 8
   Sonstigeto yield a solid, 16 gm, (59%), m.p. 252°-255° C.

Vorschrift

2-(5-chloro-7-aminoindolin-1-yl)benzamide of Example 1c (28.7 g, 0.10 mole) was dissolved in methanol/dichloromethane (DCM) solution (1:9 v/v) at 35° C. Silica gel (510 gm) was added to absorb the starting material, then the solvent was removed as much as possible under vacuum (50° C., 25 mmHg pressure for 1 hr.) The reaction mixture was then heated at 145°-155° C. and mechanically stirred for 11/2 hours. The heating was stopped when the mixture started to turn brown. The combined material was placed onto a flash chromatography column (1 kg, silica gel 60, slurry packed with DCM), eluted with DCM (16 l) and 2% CH3OH in DCM (10 l). The fractions containing the desired product were pooled and concentrated to yield a solid, 16 gm, (59%), m.p. 252°-255° C.

Quelle