Pfizer Corporation

University of Minnesota

Berkeley W Cue

Bernard S Moore

Stephen S Massett

Paul G Gassman

Philip D Hammen

Douglas J Allen

Donald K Pirie

Crystalline 2-(1-pentyl-3-guanidino)-4-(2-methyl-4-imidazolyl) thiazole

A process for production of a 2-azetidinone-1-oxoacetate of the formula ##STR1## useful as an intermediate for preparation of 2-SR.sup.2 -substituted-2-penem-3-carboxylate andtibacterial agents; R is a conventional hydroxy protecting group, R.sup.1 is certain carboxy protecting groups and ##STR2## and m and n are each 0, 1 or 2; which comprises contacting a corresponding (2-oxo-1-axetidinyl)-N-2-hydroxyacetate ester of the formula ##STR3## with manganese dioxide.

Method for preparation of azetidinone-1-oxoacetate by oxidation of the

Chiral sorbinil intermediates of the formula ##STR1## wherein R is hydrogen or benzyloxycarbonyl and Y is hydroxy or amino, processes therefor, and processes for the conversion thereof to sorbinil.

Processes and intermediates for sorbinil

Processes and intermediates useful in the preparation of bronchodilator compounds of the formula ##STR1## wherein R is hydrogen, methyl or hydroxymethyl are described. Those compounds wherein R is H or CH.sub.3 have been found to have further utility as intermediates for pirbuterol (wherein R is hydroxymethyl).

Intermediates for preparing pirbuterol and analogs

2-Guanidino-4-(2-methyl-4-imidazolyl)thiazole dihydrobromide and a one-pot, high yield process for its preparation from 2-methyl-4(or 5)-acetylimidazole.

Process for making 2-guanidino-4-(2-methyl-4-imidazolyl) thiazole

S-6-fluoro-4-aminochroman-4-carboxylic acid derivatives useful as

Sorbinil is obtained by cyclization of S-6-fluoro-4-ureidochromane-4-carboxylic acid, which is in turn obtained by resolution of racemic 6-fluoro-4-ureidochroman-4-carboxylic acid via diasteromeric salts with either D-(+)-(1-phenethyl)amine or L-(-)-ephedrine.

Sorbinil by optical resolution of precursor

3-Acetoxy or

A novel process for preparing various 2-substituted-5-aryl-1,2,3,4-tetrahydro-.gamma.-carboline derivatives is provided, which involves (1) quaternizing a corresponding 5-aryl-.gamma.-carboline compound with an appropriate aralkyl halide in the presence of sodium iodide, followed by (2) reduction of the corresponding quaternary carbolinium iodide salt intermediate with an alkali metal hydride to yield the desired final product. The latter compounds are known to be useful as tranquilizing agents, with 2-[4-(p-fluorophenyl)-4-hydroxybutyl]-5-(p-fluorophenyl)-8-fluoro-1,2,3,4- tetrahydro-.gamma.-carboline representing a preferred final product. The aforesaid carbolinium salt intermediates as well as the corresponding 5-aryl-.gamma.-carboline starting materials are all novel compounds.

Process for preparing carboline derivatives and compounds used in their

6-Fluoro-4-chromanone, a sorbinil intermediate, is regenerated from enantiomeric and mixtures of enantiomeric and racemic compounds obtained as major by-products in the synthesis of sorbinil. The regenerated intermediate is useful in the synthesis of additional sorbinil.

Regeneration of 6-fluoro-4-chromanone from by-products in the synthesis

5-Phenyl-2S-pentanol is synthesized stereospecifically from S ethyl lactate. The method provides easily purified 5-phenyl-2S-pentanol useful in the synthesis of central nervous system active (CNS) agents such as levonantradol.

Stereospecific synthesis of 5-phenyl-2S-pentanol

An aniline is converted to a 3-lower hydrocarbonthiooxindole by processes already known in the art, the product converted to a 3-halo-3-lower hydrocarbonthiooxindole by oxidative halogenation, and the product subjected to hydrolysis to form the desired isatins.

Isatin process and products

Isatin products

The invention relates to novel chemical compounds which have useful antibacterial properties and are also of value in promoting animal growth and improving animal feed efficiency. More specifically, these new chemical compounds are certain sulfonylhydrazones of 1,4-dioxoquinoxaline-2-carboxaldehyde, 4-oxoquinoxaline-2-carboxaldehyde and certain derivatives thereof of formula (I): ##STR1## wherein A is N or N .fwdarw. O; R is a member selected from the group consisting of alkyl having from one to five carbon atoms, trifluoromethyl, phenyl, npahthyl, benzyl, styryl and phenyl substituted by up to two members selected from the group consisting of Cl, F, Br, CH.sub.3, CH.sub.3 O and NO.sub.2 ; R.sup.1 is hydrogen or methyl; R.sup.2 is hydrogen or methyl; R.sup.3 is a 6- or 7-position substituent and is selected from the group H, Cl, CH.sub.3, CH.sub.3 O, SO.sub.2 NH.sub.2, SO.sub.2 NHCH.sub.3 and SO.sub.2 N(CH.sub.3).sub.2 ; R.sup.4 is a 7- or 6-position substituent and is selected from the group H, Cl and CH.sub.3 ; with the proviso that when R.sup.4 is Cl or CH.sub.3, R.sup.3 and R.sup.4 are the same.

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Gales Ferry, CT, United States of America

Berkeley W Cue