Enantioselective synthesis of pyrroloindole compounds

Patent metadata

Field	Value
Publication number	US-9969685-B2
Application number	US-201715718453-A
Country	US
Kind code	B2
Filing date	Sep 28, 2017
Priority date	Sep 28, 2016
Publication date	May 15, 2018
Grant date	May 15, 2018

Abstract

Compounds according to formula (I) or (II), wherein R 1 , R 2 , and R 3 are as defined in the specification, are versatile intermediates for the synthesis of DNA minor groove binder-alkylators having a cyclopropapyrroloindole (CPI) or seco-CPI alkylating subunit.

First claim

What is claimed is:

1. A compound of the structure according to formula (I)

wherein
R 1 is CH 2 (phenyl) wherein the phenyl group is optionally substituted with one or more of Br, Cl, F, C 1 -C 3 alkyl, O(C 1 -C 3 alkyl), CN, NH 2 , NH(C 1 -C 3 )alkyl, N(C 1 -C 3 alkyl) 2 , or CF 3 ; CH 2 (naphthyl) wherein the naphthyl group is optionally substituted with one or more of Br, Cl, F, C 1 -C 3 alkyl, O(C 1 -C 3 alkyl), CN, NH 2 , NH(C 1 -C 3 )alkyl, N(C 1 -C 3 alkyl) 2 , or CF 3 ; trimethyl silyl; triethyl silyl; triisopropyl silyl; t-butyldiphenyl silyl; triphenylsilyl; or t-butyldimethyl silyl;
R 2 is an aromatic group selected from phenyl, naphthyl, pyridyl, pyrimidinyl, imidazolyl, and pyrazolyl, the aromatic group being optionally substituted with one or more of Br, Cl, F, C 1 -C 3 alkyl, O(C 1 -C 3 alkyl), CN, NH 2 , NH(C 1 -C 3 )alkyl, N(C 1 -C 3 alkyl) 2 , or CF 3 ;
and
R 3 is trimethyl silyl, triethyl silyl, triisopropyl silyl, t-butyldiphenyl silyl, triphenylsilyl, or t-butyldimethyl silyl;
or a salt thereof.

2. A compound according to claim 1 , wherein R 1 is benzyl.

3. A compound according to claim 1 , wherein R 2 is phenyl.

4. A compound according to claim 1 , wherein R 3 is t-butydimethylsilyl.

5. A compound according to claim 1 , of the structure according to formula (Ia):

6. A compound of the structure according to formula (II)

wherein
R 1 is CH 2 (phenyl) wherein the phenyl group is optionally substituted with one or more of Br, Cl, F, C 1 -C 3 alkyl, O(C 1 -C 3 alkyl), CN, NH 2 , NH(C 1 -C 3 )alkyl, N(C 1 -C 3 alkyl) 2 , or CF 3 ; CH 2 (naphthyl) wherein the naphthyl group is optionally substituted with one or more of Br, Cl, F, C 1 -C 3 alkyl, O(C 1 -C 3 alkyl), CN, NH 2 , NH(C 1 -C 3 )alkyl, N(C 1 -C 3 alkyl) 2 , or CF 3 ; trimethyl silyl; triethyl silyl; triisopropyl silyl; t-butyldiphenyl silyl; triphenylsilyl; or t-butyldimethyl silyl;
and
R 2 is an aromatic group selected from phenyl, naphthyl, pyridyl, pyrimidinyl, imidazolyl, and pyrazolyl, the aromatic group being optionally substituted with one or more of Br, Cl, F, C 1 -C 3 alkyl, O(C 1 -C 3 alkyl), CN, NH 2 , NH(C 1 -C 3 )alkyl, N(C 1 -C 3 alkyl) 2 , or CF 3 ;
or a salt thereof.

7. A compound according to claim 6 , wherein R 1 is benzyl.

8. A compound according to claim 6 , wherein R 2 is phenyl.

9. A compound according to claim 6 , of the structure according to formula (IIa):

Assignees

• Bristol Myers Squibb Co

Inventors

• Schmidt Michael Anthony

Classifications

• C07D209/12

  Radicals substituted by oxygen atoms · CPC title

• C07D209/10 Primary

  with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring · CPC title

• C07F7/1804

  Compounds having Si-O-C linkages (Si-O-acyl linkages C07F7/1896) · CPC title

• C07F7/1852

  Chemistry & Metallurgy · mapped topic