Preparation of asymmetric cyclic ureas through a monoacylated diamine intermediate

US6218534A · kind A · utility

Assignee

• Dupont Pharmaceuticals · US

Inventors

• Benjamin R. P. Stone · West Chester, US
• Luigi Anzalone · West Chester, US
• Joseph M. Fortunak · Newark, US
• Gregory D. Harris · Wilmington, US
• Ioannis I. Valvis · Hockessin, US
• Robert E. Waltermire · Fryeburg, US

Key dates

• Filing date: Oct 5, 1998
• Grant date: Apr 17, 2001
• Expiry date: Oct 5, 2018

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D317/14
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

##STR1## A process for the preparation of asymmetric cyclic ureas of Formula (VI) starting from the diamine of Formula (I). In the process, a compound of Formual (I), wherein G is a group selected from --C(--CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.2 --)--, --C(CH.sub.2 CH.sub.3).sub.2 --, --C(CH.sub.3)(CH.sub.2 CH.sub.3)--, --C(CH.sub.2 CH.sub.2 CH.sub.2 CH.sub.3).sub.2 --, --C(CH.sub.3)(CH.sub.2 CH(CH.sub.3)CH.sub.3)--, --CH(phenyl)--, --CH.sub.2 --, --C(CH.sub.3).sub.2 --, and --C(OCH.sub.3)(CH.sub.2 CH.sub.2 CH.sub.3)--, is selectively monoacylated with an acylating agent to give an asymmetric monoacylated diamine, 2) the asymmetric monoacylated diamine is contacted with an aldehdye and a reducing agent to form a monoalkylated monoacylated diamine, 3) the monoalkylated monoacylated diamine is contacted with a strong base to form a monoalkylated de-acylated diamine, 4) the monoalkylated de-acylated diamine is contacted with 3-cyano-4-fluoro-benzaldehyde and a reducing agent to form a dialkylated diamine, and 5) the dialkylated diamine is contacted with phosgene in the presence of a base to form a compound of Formula (VI). The invention allows for scalable preparation of a wide…