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Synthesis and isolation of amorphous N-[(9S,10R,11R,13R)-2,3,10,11,12,13-hexahydro-10-methoxy-9-methyl-1-oxo-9,13-epoxy-1H,9H-diindolo[1,2,3-gh:3',2',1'-lm]pyrrolo[3,4-j][1,7]benzodiazonin-11-yl]-N-methylbenzamide

IP.com Disclosure Number: IPCOM000248596D
Publication Date: 2016-Dec-21
Document File: 2 page(s) / 215K

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Synthesis and isolation of amorphous N-[(9S,10R,11R,13R)-2,3,10,11,12,13-

hexahydro-10-methoxy-9-methyl-1-oxo-9,13-epoxy-1H,9H-diindolo[1,2,3-

gh:3',2',1'-lm]pyrrolo[3,4-j][1,7]benzodiazonin-11-yl]-N-methylbenzamide

Herein described a process for the preparation and isolation of amorphous N-[(9S,10R,11R,13R)-

2,3,10,11,12,13-Hexahydro-10-methoxy-9-methyl-1-oxo-9,13-epoxy-1H,9H-diindolo[1,2,3-gh:3',2',1'-

lm]pyrrolo[3,4-j][1,7]benzodiazonin-11-yl]-N-methylbenzamide (Compound I), which is a multi-target

protein kinase inhibitor, having the structure:

Chemical formula: C35H30N4O4

Molecular mass: 570.64 g/mol

Experimental part:

Synthesis of Compound I:

The starting material of the synthesis, (9S,10R,11R,13R)-2,3,10,11,12,13-Hexahydro-10-methoxy-9-

methyl-11-(methylamino)-9,13-epoxy-1H,9H-diindolo[1,2,3-gh:3',2',1'-lm]pyrrolo[3,4-

j][1,7]benzodiazonin-1-one can be produced by any process described in the literature, for example

according to Exp 1 and 2 in US4,107,297. 1 g from the obtained product was dissolved in DMF. Base was

added, which can be N,N-diisopropyl-ethyl-amine (0.54 ml), Triethyl-amine (0.44 ml) or Dimethyl-amino-

pyridine (0,392 g) and then benzoyl-chloride (0.29 ml) was dropped into the mixture.

Isolation of Compound I:

After reaction completion, the mixture was diluted with iBuOAc (125 ml), washed with saturated NaHCO3

solution and water. Compound I was precipitated, after evaporation of organic phase by addition of n-

Heptane (300 ml) at room temperature. The s...