Pfizer Corporation

Stephen S Massett

Berkeley W Cue

Philip D Hammen

George Joseph Quallich

Peter Robert Rose

Lewin Theophilus Wint

Harry A Watson, Jr

Two crystalline polymorphic forms of (2-Benzhydryl-1-azo-bicyclo&lsqb;2.2.2&rsqb;oct-3-yl)-(5-isopropyl-2-methoxybenzyl)-amine citrate monohydrate (the monohydrates) are Form A and Form B. The pharmaceutical composition containing at least one of these polymorphs has advantageous stability for formulation to treat acute emesis in patient receiving chemotherapy. The administration of this pharmaceutical composition is conventional oral by preferably tablet or capsule and intravenous. A method of making A and B Forms is also disclosed.

Polymorphs of a crystalline azo-bicyclo (2.2.2) oct-3-yl amine citrate and their pharmaceutical compositions

1,1-Di(p-fluorophenyl)urea, 2-carbobenzoxy-8-fluoro-5-(p-fluorophenyl)-2,3,4,5-tetrahydro-1H-pyrido[4, 3-b]indole, an efficient process for converting the former to the latter, further comprising conversion of the latter to 8-fluoro-5-(p-fluorophenyl)-2-[4-(p-fluorophenyl)-4-hydroxybutyl)]-2,3,4,5 -tetrahydro-1H-pyrido[4,3-b]indole (flutroline) or to 8-fluoro-5-(p-fluorophenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (an alternative flutroline intermediate).

1,1-bis(p-fluorophenyl)urea

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

1,1-Di(p-fluorophenyl)urea, 2-carbobenzoxy-8-fluoro-5-(p-fluorophenyl)-2,3,4,5-tetrahydro-1H-pyrido[4, 3-b]indole, an efficient process for converting the former to the latter, further comprising conversion of the latter to 8-fluoro-5-(p-fluorophenyl)-2-[4-(p-fluorophenyl)-4-hydroxybutyl)-]2,3,4,5 -tetrahydro-1H-pyrido[4,3-b]indole (flutroline) or to 8-fluoro-5-(p-fluorophenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (an alternative flutroline intermediate).

2-Carbobenzoxy-8-fluoro-5-(p-fluorophenyl-2,3,4,5-tetrahydr

3-Acetoxy or

Processes and intermediates useful in the preparation of flutroline

8-Fluoro-5-(p-fluorophenyl)-2-[4-(p-fluorophenyl)-4-hydroxybutyryl]-2,3,4,5 -tetrahydro-1H-pyrido[4,3-b]-indole; processes therefor; and process for the conversion to flutroline.

Compound,

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

6-(Triphenylmethylamino)-2,2-dimethyl-3-(N-[p-methoxybenzyl]carbamoyl)penam -dimethylsulfoxide complex as a useful intermediate leading to the synthesis of antibacterial 6-acylamino-2,2-dimethyl-3-(5-tetrazolyl)penams.

Growing community of inventors

Groton, CT, United States of America

Stephen S Massett