Regio-selective synthesis of imidazo[1,2-a]pyrimidines

US11325912B2 · kind B2 · utility

Assignee

• Genentech, Inc. · US

Inventors

• Kyle Bradley Pascual Clagg · San Francisco, US
• Nicholas Andrew White · San Francisco, US
• Haiming Zhang · Pennington, US
• Francis Gosselin · South San Francisco, US
• William Nack · Glenview, US
• Paul O'Shea · Westmount, CA

Key dates

• Filing date: May 7, 2020
• Grant date: May 10, 2022
• Expiry date: May 7, 2040

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02P20/55
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

A method of regio-selectively synthesizing an imidazo-pyrimidine compound of formulae (XXa) or (XXb) comprising a step of coupling a first compound of formula XX-P1a or XX-P1b with a second compound of formula XX-P2 This annulation reaction between β-ethoxy acrylamides and phosphorylated aminoimidazoles to furnish imidazo[1,2-a]pyrimidin-amines relies on steering effects from endocyclic and exocyclic phosphorylated aminoimidazoles. The reaction furnishes either 2-amino or 4-amino constitutional isomers of imidazo[1,2-a]pyrimidines with good yields and ranges of 90:10-99:1 regio-selectivity. The reaction is useful in the synthesis of various tracer molecules used in the study of neurological conditions such as where R3 and R4 together with the imidazole ring atoms to which they are bonded form a phenyl ring and the products are substituted benzimidazopyrimidines. The reaction can be generalized to form imidazo[1,2-a]pyrimidines substituted at either of their 2- and 4-positions by alkoxy or thioalkyl groups.