Azatadine maleate

58 g of diphenimide were placed in a Soxhiet thimble and extracted for about 3 days with a boiling mixture of 9.0 g of lithium aluminum hydride in 600 cc of sodium-dried ether. Excess lithium aluminum hydride was then decomposed cautiously with water and the mixture was filtered through a filter aid by suction. The filtrate consisted of two layers. The ether layer was separated and dried with anhydrous potassium carbonate and acidified with alcoholic hydrochloric acid to give 6,7-dihydro-5H-dibenz[c,e] azephine hydrochloride, MP about 287 -289°C. 

One gram of 6,7-dihydro-5H-dibenz[c,e] azepine hydrochloride was dissolved in water, made alkaline with concentrated ammonia, and the resultant base extracted twice with benzene. The benzene layers were combined, dried with anhydrous potassium carbonate, and mixed with 0.261 g of allyl bromide at 25°-30°C. The reaction solution became turbid within a few minutes and showed a considerable crystalline deposit after standing 3 A days. The mixture was warmed VA hours on the steam bath in a loosely-stoppered flask, then cooled and filtered. The filtrate was washed twice with water and the benzene layer evaporated at diminished pressure. The liquid residue was dissolved in alcohol, shaken with charcoal and filtered. Addition to the filtrate of 0.3 gram of 85% phosphoric acid in alcohol gave a clear solution which, when seeded and rubbed, yielded 6-allyl-6,7-dihydro-5H-dlbenz[c,e] azepine phosphate, MP about 211°-215°C with decomposition. 

Schmidt, R. A. and Wenner, W. U.S. Patent 2,693,465 November 2, 1954 assigned to Hoff-mann-La Roche, Inc. 

Chemical Name 6,11 -Dihydro-11-(1-methyl-4-piperidinylidene)-5H-benzo[5,6] cyclohepta-[1,2-b] pyridine 

N-Methyl-4-chloropiperidine Polyphosphoric Acid 4-Aza-10,11 -dihydro-5-H-dibenzo-[a,d] -cycloheptene-5 one 

Preparation of 4-aza-5-(N-methyl-4-piperidyll-10,11-dihydro-5H-dibenzo[a,d] cycloheptene-S-ol Add 17.4 g of N-methyl-4chloropiperidine to a stirred mixture containing 3.2 g of magnesium, 20 ml of anhydrous tetrahydrofuran, 1 ml of ethyl bromide and a crystal of iodine. Reflux for two hours, cool to 30°-35 C and add a solution of 13 g of 4-aza-10,11 -dihydro-5H-dibenzo [a,d] cycloheptene-5-one in 25 ml of tetrahydrofuran. Stir for five hours, remove the solvent by distillation in vacuo and add 250 ml of ether. Add 100 ml of 10% ammonium chloride solution and extract the mixture with chloroform. Concentrate the chloroform solution to a residue and recrystallize from isopropyl ether obtaining 20 g of the carbinol, 

Preparation of4-aza-5-(N-methyl-4-piperidyl)-10,1 l-dihydro-BH-dibenzofa.d]cycioheptene- 

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Azatadine maleate Chlorprothixene Cyproheptadine iphenidol Flupentixol Heptabarbitol Mepivacaine Methadone HCI Methallenestril Methohexital sodium Oxitropium bromide Pipethanate ethobromide Pyrithyidione Ethyl bromoacetate Aceclidine... 

Formulation(s) syrup 0.5 mg (as dimaleate) tabl. 1 mg (azatadine maleate)... 

Piperidine derivatives azatadine maleate cyproheptadine hydrochloride desloratadine... 

Bulk Azatadine maleate TLC — Silica (above) As above Char GC/HPLC [11,158] [1]... 

Azatadine, 367 Azatadine maleate, 367 Azathioprine, 368 Azene, 485 Azepine, 366 Azide, 454... 

Tarasido JC. Azatadine maleate/pseudoephedrine sulfate repetabs versus placebo in the treatment of severe seasonal allergic rhinitis. J Int Med Res 1980 8(6) 391-4. 

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