Roche Colorado Corporation

Corden Pharma Colorado, Inc.

Bradley S DeHoff

Peter John Harrington

Hiralal N Khatri

Richard A Gabel

Barry Thomas King

Paul Adam Bury

John Edward Crider

Robert Thad Carr, Ii

Robert Thad Carr Ii

The present invention relates to the preparation of insulinotropic peptides that are synthesized using a solid and solution phase ('hybrid') approach. Generally, the approach includes synthesizing three different peptide intermediate fragments using solid phase chemistry. Solution phase chemistry is then used to add additional amino acid material to one of the fragments. The fragments are then coupled together in the solution phase. The use of a pseudoproline in one of the fragments eases solid phase synthesis of that fragment and also eases subsequent solution phase coupling of this fragment to other fragments. The present invention is very useful for forming insulinotropic peptides such as Exenatide(1-39) and its natural and non-natural counterparts.

Insulinotropic peptide synthesis using solid and solution phase combination techniques

The present invention provides a process for preparing 1,2-diheteroethylene sulfonamide of the formula: ##STR1## by reacting a pyrimidine monohalide of the formula: ##STR2## with a mono-protected 1,2-diheteroethylene anion of the formula M.sub.1 XCH.sub.2 CH.sub.2 YR.sub.5 and removing the protecting group, wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, Z, X, Y, M, M.sub.1 and W are defined herein.

Preparation of sulfonamides

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Longmont, CO, United States of America

Bradley S DeHoff