Intermediates and methods for synthesizing calicheamicin derivatives

Patent metadata

Field	Value
Publication number	US-9902691-B2
Application number	US-201415030563-A
Country	US
Kind code	B2
Filing date	Oct 28, 2014
Priority date	Nov 4, 2013
Publication date	Feb 27, 2018
Grant date	Feb 27, 2018

Abstract

The present invention relates to intermediates of Formula I

and to methods of synthesizing and purifying calicheamicin derivatives.

First claim

What is claimed is:

1. A compound of Formula I

wherein R 12 is selected from straight and branched-chain C 1 -C 8 alkyl;
each R 10 is independently selected from hydrogen, R 12 and —OR 12 ;
R 8 and R 9 are each independently selected from hydrogen and straight and branched-chain C 1 -C 8 alkyl, wherein each said alkyl for R 8 and R 9 is independently optionally substituted by —NH 2 , —NHR 11 , —NR 11 R 13 , —OR 11 , —OH, or —SR 11 , wherein each R 11 and each R 13 are independently selected from straight and branched-chain C 1 -C 5 alkyl;
r is an integer 0 or 1;
G is oxygen or sulfur;
Z 1 is H or straight or branched-chain C 1 -C 5 alkyl;
Ar is 1,2-, 1,3-, or 1,4-phenylene optionally substituted with one, two or three groups independently selected from straight or branched-chain C 1 -C 6 alkyl, —OR 14 , —SR 14 , halogen, nitro, —COOR 14 , —C(═O)NHR 14 , —O(CH 2 ) n COOR 14 , —S(CH 2 ) n COOR 14 , —O(CH 2 ) n C(═O)NHR 14 , and —S(CH 2 ) n C(═O)NHR 14 , or Ar is a 1,2-, 1,3-, 1,4-, 1,5-, 1,6-, 1,7-, 1,8-, 2,3-, 2,6-, or 2,7-naphthylidene optionally substituted with one, two, three, or four groups independently selected from straight or branched-chain C 1 -C 6 alkyl, —OR 14 , —SR 14 , halogen, nitro, —COOR 14 , —C(═O)NHR 14 , —O(CH 2 ) n COOR 14 , —S(CH 2 ) n COOR 14 , —O(CH 2 ) n C(═O)NHR 14 , and —S(CH 2 ) n C(═O)NHR 14 ;
wherein each R 14 is independently selected from (C 1 -C 5 )alkyl and each R 14 is independently optionally substituted with one or two groups selected from —OH, —(C 1 -C 4 )alkyl, and —S(C 1 -C 4 )alkyl;
each n is an integer independently selected from 0, 1, 2, 3, 4, and 5;
W is selected from —O—, —S—, —C(═O)NH—, —NHC(═O)—, and —NR 15 —, wherein R 15 is a (C 1 -C 5 )alkyl and R 15 is optionally substituted with one or two groups selected from —OH, —(C 1 -C 4 )alkyl, and —S(C 1 -C 4 )alkyl; and
Y is a straight or branched-chain (C 1 -C 6 )alkylene group or a straight or branched-chain (C 2 -C 6 )alkenylene group.

2. A compound of claim 1 , wherein each R 10 is hydrogen.

3. A compound of claim 2 , wherein R 12 is methyl.

4. A compound of claim 3 having the structure

5. A compound of claim 1 , wherein R 8 and R 9 are methyl, r is 0, G is oxygen, Z 1 is methyl, Ar is 1,4-phenylene, W is —O—, and Y is —(CH 2 ) 3 —.

Assignees

• Pfizer

Inventors

• Dugger Robert Wayne
• Letendre Leo Joseph
• Patel Vimalkumar Babubhai
• Prashad Amarnauth Shastrie
• Zhang Chunchun

Classifications

• C07C251/02

  containing imino groups · CPC title

• C07C323/60 Primary

  with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms · CPC title

• C07H15/26

  Acyclic or carbocyclic radicals, substituted by hetero rings · CPC title

• C07C319/20 Primary

  by reactions not involving the formation of sulfide groups · CPC title

• C07C319/28 Primary

  Separation; Purification · CPC title