Genentech, Inc.

Paul D O'Shea

Francis Gosselin

Haiming Zhang

Kyle Bradley Pascual Clagg

Nicholas Andrew White

William Nack

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 &#x3b2;-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 Rand Rtogether 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.

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

A method of synthesizing comprising a step of making an imidazo-pyrimidine compound by coupling a first compound of formula (II) with a second compound of formula (III)  Followed by a deprotection and tosylation step. The methods are able to produce an isotopically substituted molecule having upwards of 95% purity relative to non-isotopically substituted molecules. The invention further comprises compounds of formula: 

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Princeton, NJ, United States of America

Paul D O'Shea