Camptothecin intermediates and method of making camptothecin and comptothecin analogs
US5475108A · kind A · utility
Assignee
Inventors
Key dates
| Filing date | Aug 31, 1993 |
| Grant date | Dec 12, 1995 |
| Priority date | — |
| Expiry date | Aug 31, 2013 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07D491/22
- WIPO fieldOrganic fine chemistry
- WIPO sectorChemistry
Abstract
Disclosed are new methods of making camptothecin and camptothecin analogs defined by Formula I: ##STR1## wherein R is loweralkyl; R.sub.1 is H, loweralkyl, loweralkoxy, or halo; and R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are each independently H, amino, hydroxy, loweralkyl, loweralkoxy, loweralkylthiol, di(loweralkyl)amino, cyano, methylenedioxy, formyl, nitro, halo, trifluoromethyl, aminomethyl, azido, amido, hydrazino, or any of the twenty standard amino acids bonded to the A ring via the amino-nitrogen atom. The methods comprise cyclizing a compound of Formula IV: ##STR2## wherein X is Br or I, and Y is H, by an Aryl-to-Aryl free radical coupling reaction to yield a compound of Formula I. Compounds of Formula IV are made by alkylating a compound of Formula III: ##STR3## wherein R is loweralkyl and Y is H with a compound of Formula II-x: ##STR4## wherein X is a Br or I and V is hydroxy, by a Mitsunobu reaction to yield the compound of Formula IV.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.