Merck + Co., Inc.

Zeneca Limited

Paul Sohar

David J Mathre

Thomas J Blacklock

Edward J Grabowski

Richard F Shuman

George M Love

Leonard M Weinstock

Andrew John Blacker

John W Butcher

Zhiguo Jake Song

Guo-Jie Ho

Todd K Jones

Lyndon C Xavier

F Edward Roberts

Erwin F Schoenewaldt

Khateeta M Emerson

Theresa R Lamanec

Anthony M DeMarco

David Moody

Julie J Mohan

Lynn M Brown

Imidazolmethyloxy-substituted tricyclo-macrolide immunosuppressants are prepared by reacting a tricyclo-macrolide with an imidazolmethyl trichloroacetimidate in the presence of an acid. The invention further provides a crystalline salt of imidazolmethyloxy-substituted tricyclo-macrolide, as well as novel compounds useful in the process of the present invention.

Process for the preparation of imidazolyl macrolide immunosuppressants

This invention is concerned with an improved process for the synthesis of hydroxysulfone, which is a key intermediate in the synthesis of carbonic anhydrase inhibitors, especially dorzolamide. Carbonic anhydrase inhibitors are known to be effective in treating elevated intraocular pressure or glaucoma.

Synthesis of hydroxysulfone and related compounds

Process to derivatives of piperizinylcamphorsulfonyl oxytocin antagonists

A key step in the synthesis of 5,6-dihydro-(S)-4-(ethylamino)-(S)-6-methyl-4H-thieno�2,3-b!thiopyran-2-su lfonamide 7,7-dioxide (dorzolamide) and related compounds is a Ritter reaction with an unexpected tendency to proceed with retention of chirality.

Enantioselective synthesis of

This invention is concerned with an improved process for the synthesis of and intermediate en route to 5,6-dihydro-(s)-4-(ethylamino)-(s)-6-methyl-4h-thieno[2,3-b]thiopyran-2-su lfonamide 7,7-dioxide and related compounds. The instant process reduces the reaction time for the synthesis of the key intermediate from 3 to 4 days to from about 2 to about 4 hours while retaining the high enantiomeric purity of the product.

Synthesis of an intermediate for the preparation of

5,6-Dihydro-4-(R-amino)-4H-thieno[2,3-b]-thiopyran-2-sulfonamide-7,7-dioxid e is a potent carbonic anhydrase inhibitor useful in the treatment of ocular hypertension and glaucoma. The S-(+)-enantiomer of that compound, the more active enantiomer, is prepared by a process involving an intermediate step of an enantioselective reduction of a carbonyl group employing an oxazaborolidine chiral catalyst.

Enantiospecific synthesis of

Compounds classified as 5,6-dihydro-4-alkylamino-4H-thieno (or furo) [2,3-b]thiopyran-2-sulfonamide-7,7-dioxide are carbonic anhydrase inhibitors useful in the treatment of ocular hypertension, and most of the carbonic anhydrase inhibitory activity resides in only one of the enantiomers. The undesired enantiomer is utilized by racemization by thermolysis of an N-acyl derivative in a basic environment followed by removal of the acyl group. The racemate may then be resolved into the enantiomers.

Process for racemizing an enantiomer of

The present invention relates to an improved process for the preparation of the compounds of formula (I) ##STR1## which involve the direct oxidation without N-protection of the compound of the formula (II) ##STR2##

Process for the preparation of 1,1-dioxo-7-substituted cephems

(S)-Alkyl 3-(thien-2-ylthio)butyrate and analogs are intermediates in the synthesis of the chiral (S,S)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfon amide-7,7-dioxide and analogs thereof, topically effective carbonic anhydrase inhibitors useful in the treatment of ocular hypertension and glaucoma.

(S)-Alkyl 3-(thien-2-ylthio)butyrate and analogs and synthesis thereof

An improved process for preparing the antibiotic compound 7.beta.-(2-thienylacetamido)-7-methoxy-3-carbamoyloxymethyl-3-cephem-4-car boxylic acid, from the N-blocked esters of the compound 7.beta.-(D-5-amino-5-carboxyvaleramido)-3-carbamoyloxymethyl-7-methoxy-3-c ephem-4-carboxylic acid (Cephamycin C), by conducting the transacylation of the latter in a homogeneous solution containing a trimethylsilyl enol ether.

Process for the preparation of cephamycin antibiotics

An improved process for preparing the antibiotic compound 7.beta.-(2-thienylacetamido)-7-methoxy-3-carbamoyloxymethyl-3-cephem-4-car boxylic acid, from the N-blocked esters of the compound 7.beta.-(D-5-amino-5-carboxyvaleramido)-3-carbamoyloxymethyl-7-methoxy-3-c ephem-4-carboxylic acid (Cephamycin C), by conducting the transacylation of the latter in a homogenous solution containing N-trimethylsilyl loweralkyl carbamates.

The invention disclosed herein relates to a novel process for preparing the monomer, 3-[N-(3-chloropropyl)methylamino]-N,N,N-trimethyl-propan-1-aminium chlorid e, which comprises reacting N,N-bis(3-chloropropyl)methylamine with trimethylamine. The 3,3-ionene monomer thus obtained is a key intermediate for making the linear, unbranched, non-cross-linked polymer, poly-[{methyl-(3-trimethylammoniopropyl)imino}trimethylene dichloride], which is valuable as an oral bile acid sequestrant.

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Warren, NJ, United States of America

Paul Sohar