Abbott Laboratories Corporation

Other

Abbvie Inc.

Michael S Allen

Jien-Heh J Tien

Hing L Sham

Thomas J Sowin

Daniel S Reno

Anthony Ralph Haight

Howard E Morton

Timothy L Stuk

M Robert Leanna

Linda M Lijewski

Daniel W Norbeck

Chen Zhao

Laura Melcher

Timothy A Robbins

Francis A Kerdesky

Denton C Langridge

David Scarpetti

Steven J Wittenberger

Lawrence Kolaczkowski

Steven A King

Sou-Jen Chang

Daniel J Plata

Eric J Stoner

Stephen L Condon

Ramiya H Premchandran

Subhash R Patel

Hemant H Patel

John A DeMattei

Paul J Nichols

Sukumar Manna

Paul Nichols

John J Demattei

Dale J Kempf

Arthur J Copper

The invention relates to a process for preparing quinoline-substituted carbonate and carbamate compounds, which are important intermediates in the synthesis of 6-O-substituted macrolide antibiotics. The process employs metal-catalyzed coupling reactions to provide a carbonate or carbamate of formula (I) or (II) or a substrate that can be reduced to obtain the same.

Preparation of quinoline-substituted carbonate and carbamate derivatives

The present invention discloses a process for the preparation of a hydroxymethylthiazole compound having formula 3: The process of the invention comprises reacting a halomethyl thiazole having the formula: ##STR1## with water, at an elevated temperature. Optionally, the reaction can be carried out in the presence of a base, such as sodium carbonate, which can react with any acid formed. In the process of the invention, X is a halogen atom; and R.sup.6 is selected from the group consisting of hydrogen, and halogen atoms. The invention also contemplates the preparation of acid addition salts of the hydroxymethylthiazole, compound 3.

Process for the preparation of 5-hydroxymethylthiazoles

Intermediates and processes are disclosed which are useful for the preparation of a substantially pure compound of the formula: ##STR1## wherein R.sub.6 and R.sub.7 are each hydrogen or R.sub.6 and R.sub.7 are independently selected from ##STR2## wherein R.sub.a and R.sub.b are independently selected from hydrogen, loweralkyl and phenyl and R.sub.c, R.sub.d and R.sub.e are independently selected from hydrogen, loweralkyl, trifluoromethyl, alkoxy, halo and phenyl; and ##STR3## wherein the naphthyl ring is unsubstituted or substituted with one, two or three substituents independently selected from loweralkyl, trifluoromethyl, alkoxy and halo; or

Process for the preparation of a substituted 2.5-diamino-3-hydroxyhexane

A process for the preparation of 5-hydroxymethylthiazole comprises reacting a compound of the formula, ##STR1## with a carboxylic acid salt (optimally in the presence of a quaternary ammonium salt) and hydrolyzing the resulting ester. Subsequent dechlorination gives 5-hydroxymethylthiazole.

Process for preparation of 5-hydroxymethylthiazole

Intermediates and processes are disclosed which are useful for the preparation of a substantially pure compound of the formula: ##STR1## wherein R.sub.6 and R.sub.7 are each hydrogen or R.sub.6 and R.sub.7 are independently selected from ##STR2## wherein R.sub.a and R.sub.b are independently selected from hydrogen, loweralkyl and phenyl and R.sub.c, R.sub.d and R.sub.e are independently selected from hydrogen, loweralkyl, trifluoromethyl, alkoxy, halo and phenyl; and ##STR3## wherein the naphthyl ring is unsubstituted or substituted with one, two or three substitutents independently selected from loweralkyl, trifluoromethyl, alkoxy and halo; or R.sub.6 is as defined above and R.sub.7 is R.sub.7a OC(O)-- wherein R.sub.7a is loweralkyl or benzyl; or R.sub.6 and R.sub.7 taken together with the nitrogen atom to which they are bonded are ##STR4## wherein R.sub.f, R.sub.g, R.sub.h and R.sub.i are independently selected from hydrogen, loweralkyl, alkoxy, halogen and trifluoromethyl and R.sub.8 is hydrogen or --C(O)R' wherein R' is loweralkyl, alkoxy, benzyloxy or phenyl wherein the phenyl ring is unsubstituted or substituted with one, two or three substituents independently selected from loweralkyl, trifluoromethyl, alkoxy and halo; or an acid addition salt thereof.

Process for the preparation of a disubstituted

Process for the preparation of a substituted 2,5-diamino-3-hydroxyhexane

A retroviral protease inhibiting compound of the formula: ##STR1## is disclosed.

Retroviral protease inhibiting compounds

Intermediates and processes are disclosed which are useful for the preparation of a substantially pure compound of the formula: ##STR1## wherein R.sub.6 and R.sub.7 are each hydrogen or R.sub.6 and R.sub.7 are independently selected from ##STR2## wherein R.sub.a and R.sub.b are independently selected from hydrogen, loweralkyl and phenyl and R.sub.c, R.sub.d and R.sub.e are independently selected from hydrogen, loweralkyl, trifluoromethyl, alkoxy, halo and phenyl; and ##STR3## wherein the naphthyl ring is unsubstituted or substituted with one, two or three substitutents independently selected from loweralkyl, trifluoromethyl, alkoxy and halo; or

Process for the preparation of a substituted 2,5-Diamino-3-Hydroxyhexane

Process for the prepartation of a substituted 2,5-diamino-3-hydroxyhexane

A substantially pure compound of formula: ##STR1## wherein R.sub.6 and R.sub.7 are independently selected from ##STR2## wherein R.sub.a and R.sub.b are independently selected from hydrogen, loweralkyl and phenyl and R.sub.c, R.sub.d and R.sub.e are independently selected from hydrogen, loweralkyl, trifluoromethyl, alkoxy, halo and phenyl; and ##STR3## wherein the naphthyl ring is unsubstituted or substituted with one, two or three substitutents independently selected from loweralkyl, trifluoromethyl, alkoxy and halo; or

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Silver Lake, WI, United States of America

Michael S Allen