Syntex (u.s.a.) Inc.

Roche Palo Alto LLC

Hoffmann-la Roche Inc.

Eric Roy Humphreys

Humberto Bartolome Arzeno

Christopher R Roberts

Charles Alois Dvorak

Paul Ross Fatheree

Colin C Beard

Lawrence Emerson Fisher

Yeun-Kwei Han

Douglas L Wren

Sam Linh Nguyen

Steven D Axt

Jan P Lund

Jim-wah Wong

Hans Iding

Keshab Sarma

Stephen Matthew Lynch

Terrence Joseph Connolly

Jean-Michel Adam

Shaoning Wang

Christophe Pfleger

Justin Philip Vitale

Keena Lynn Green

Gary R Lee

Xianqing Shi

Daniel Fishlock

Patrick Finbar McGarry

Pankaj D Rege

Robert Patrick Farrell

Anton Constantinescu

Marian Zajac

The present invention is concerned with a novel process for the preparation of a compound of formula I and its hydrates  The compounds of formula I and the corresponding hydrates are pharmaceutically active substances.

(3,4-dichloro-phenyl)-((S)-3-propyl-pyrrolidin-3-yl)-methanone hydrochloride and manufacturing processes

A method for preparing a compound of formula I the method comprising treating a compound of formula d with an iodination reagent, to form the compound of formula I, wherein R, Rand Rare as defined herein.

Process for synthesis of phenoxy diaminopyrimidine derivatives

A method comprising: with vitride, to form an aminopropyl indole compound of formula i wherein m, Ar, Rand Rare as defined herein. The compounds prepared by the method of the invention are useful as monoamine reuptake inhibitors useful for treatment of CNS indications.

Methods for synthesis of 3-amino-1-arylpropyl indoles

Process for preparing a 2-(2-amino-1, 6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol derivative

Process for preparing intermediates of formula (III)

Process for preparing a 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol derivative

Intermediates of Formula (III) ##STR1## wherein P.sup.1 is hydrogen or an amino-protecting group, R is lower alkyl, allyl or aralkyl, and Z is hydrogen, lower alkyl, aryl or aralkyl; and Formula (VI) ##STR2## wherein P.sup.1 is hydrogen or an amino-protecting group, P.sup.2 is an amino protecting group, and Z is hydrogen, lower alkyl, aryl or aralkyl, are useful in a novel process for preparing the mono-L-valine ester of 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol (ganciclovir). The mono-L-valine ester of ganciclovir and its pharmaceutically acceptable salts are of value as antiviral agents with improved absorption.

Process for preparing a

Process and novel intermediates for preparing the L-mono-valine ester of 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol and its pharmaceutically acceptable salts. The present process and intermediates provide for reduced impurities in the mono-valine ester end-product and lower overall production costs. The process involves the condensation of a silylated guanine compound with a substituted glycerol derivative and esterification of this product with an L-valine derivative. These mono-valine products are of value as antiviral agents with improved absorption.

Process for preparing a 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)

Process and novel intermediates for preparing the mono-L-valine ester of 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol ganciclovir) and its pharmaceutically acceptable salts. The present process and monoester intermediates provide for mono-esterification by an L-valine derivative, resulting in a monocarboxylate-monovalinate which is then selectively hydrolyzed under basic or enzymatic conditions to give the monovaline ester of ganciclovir in high yield and purity. These products are of value as antiviral agents with improved absorption.

Process for preparing the L-monovaline ester of 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol and its pharmaceutically acceptable salts. The present process provides an N,O-bis-trityl intermediate of 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol which allows for mono-esterification by an L-valine derivative. These products are of value as antiviral agents with improved absorption.

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San Bruno, CA, United States of America

Eric Roy Humphreys