Ergotamine hydrochloride

One part by weight of compound II in the form of a salt, e.g. ergotamine hydrochloride, is heated with four parts by weight of anhydrous hydrazine for one hour at 90° C. The reaction mixture is then diluted, preferably with water, the excess hydrazine and water distilled off azeotropically, and the residue shaken between aqueous tartaric acid and an inert water-immiscible solvent, e.g. chloroform or ether. The aqueous phase is made alkaline and the final product taken up in a water-immiscible solvent, e.g. chloroform. 

A solution of 1.6 g. of 1-methyl-ergotamine hydrochloride in 6.4 cc. of anhydrous hydrazine are heated for 1 hour at 90°, the mixture diluted with 50 cc. of water, the water and the hydrazine hydrate are distilled off and after the addition of a further 6.4 cc. of anhydrous hydrazine the remaining procedure is repeated. The residue is then shaken between a diluted tartaric acid solution and chloroform. The bases liberated after the tartaric acid solution has been made alkaline are shaken with chloroform and the crude product remaining after evaporation of the chloroform is chromatographed on a column of 25 g. of aluminium oxide. l-methyl-c -iso-lysergic acid hydrazide is washed into the filtrate with chloroform containing 0.5% of ethanol. The compound crystallizes from ethanol in the form of nice leaflets. Melting point 201-204°. [a]D20=+400° (c.=0.5 in pyridine). Keller s colour reaction blue. 

Diphenhydramine hydrochloride, 3,173 Diphenoxylate hydrochloride, 7,149 Disulflram, 4, 168 Dobutamine hydrochloride, 8,139 Droperidol, 7,171 Echothiophate iodide, 3,233 Epinephrine, 7, 193 Ergotamine tartrate, 6,113 Erythromycin, 8,139 Erythromycin estolate, 1, 101 2, 573 Estradiol valerate, 4,192 Ethambutol hydrochloride, 7,231 Ethynodiol diacetate, 3,253 Fenoprofen calcium, 6,161 Flucytosine, 5,115 Fludrocortisone acetate, 3, 281 Fluorouracil, 2,221 Fluoxymesterone, 7,251 Fluphenazine enanthate, 2, 245 4,523 Fluphenazine hydrochloride, 2,263 4,518 Gluthethimide,5,139 Gramicidin, 8,179 Griseofulvin, 8,219 Halcinonide, 8,251 Halothane, 1, 119 2,573 Hexetidine, 7,277 Hydralazine hydrochloride, 8,283 Hydroflumethiazide, 7,297 Hydroxyprogesterone caproate, 4,209 Hydroxyzine dihydrochloride, 7,319 Iodipamide, 3,333 Isocarboxazid, 2, 295... 

Conversion of isomer Lilia with lysergic acid chloride hydrochloride (IVa) in chloroform, with the addition of tributylamine, yielded a compound whose chemical, physical, and pharmacological properties were identical with those of the natural alkaloid ergotamine. Thus, the total synthesis of this alkaloid was accomplished, lysergic acid having already been synthesized at an earlier date (50). 

Dyclonine Hydrochloride Ergotamine Tartrate Trimethobenzamide Hydro-... 

The reaction above is illustrated for ergotamine, but the process is just as valid when a mixture of amides is used as extracted from the crop. Further, the crop amides have been left in the freebase form, so the procedure given in example 5 in US patent 3,239,530 is used. This is superior to trying to make a hydrochloride salt of the amides, as suggested in example 1, because this would expose the active ingredients to loss and destruction during the unnecessary handling. 

A woman who had regularly and uneventfully taken Migral (ergotamine tartrate 2 mg, cyclizine hydrochloride 50 mg, caffeine 100 mg) on a number of previous occasions, took one tablet during a course of treatment with erythromycin 250 mg every 6 hours. Within 2 days she developed severe ischaemic pain in her arms and legs during exercise, with a burning sensation in her feet and hands. When admitted to hospital 10 days later, her extremities were cool and cyanosed. Her pulse could not be detected in the lower limbs. ... 

Migril (Ergotamine tartrate, cyclizine hydrochloride and caffeine hydrate). Wockhardt UK Ltd. Summary of product cha teristics, December 2003. 

The peroxide value is a measure of the number of peroxide bridges in the fat. Fats or oils with a low peroxide number (<0.5) are used for the processing of easily oxidisable substances. Examples are ergotamine tartrate and chlorpromazine hydrochloride in fatty suppositories. 

Examples of other substances that may contain more than 4 % impurities are dexamethasone sodium phosphate, ergotamine tartrate, erythromycin, codergocrine mesilate, cyanocobalamin, hydroxycobalamin, thiamine hydrochloride and ferrous fumarate. 

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