28910-91-0

The invention discloses a preparation method of flualprazolam, and relates to the technical field of medicine synthesis. The preparation method of the flualprazolam comprises the following steps: by taking phosphorus pentasulfide as a vulcanizing reagent, vulcanizing carbonyl groups of 7-chloro-1,3-dihydro-5-(2-fluorophenyl)-3H-1,4-benzodiazepine-2-one to obtain an intermediate; and adding the intermediate and acethydrazide into an organic solvent, and reacting to obtain flualprazolam. The synthesis method provided by the invention only needs two steps and is simple to operate, so the reactiontime is greatly shortened, the reaction cost is reduced, and the reaction efficiency is improved; and the reaction process conditions are mild, and the reagent toxicity is low, so the synthesis process is safe and environment-friendly.

The invention discloses 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolbenzo[1,4]benzodiazepine with a structure represented by a formula shown in the description. A preparation method for the8-chloro-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolbenzo[1,4]benzodiazepine comprises the following steps: (1) synthesizing a compound B from a compound A; (2) synthesizing a compound C from the compound B; and (3) synthesizing the 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolbenzo[1,4]benzodiazepine compound D from the compound C. Shown by application researches on the 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolbenzo[1,4]benzodiazepine, the prepared 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolbenzo[1,4]benzodiazepine can be applied to reference materials for detection and identification work of organs of public security. The technical scheme of the invention achieves the following beneficial technical effects that an optimal synthesis route for synthesizing the 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolbenzo[1,4]benzodiazepine is optimized; the target object, i.e., the 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolbenzo[1,4]benzodiazepine is separated and purified, and thus, the purity of the 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolbenzo[1,4]benzodiazepine reaches 99% or more; and the prepared 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolbenzo[1,4]benzodiazepine can directly serve as a reference substance for the detection and identification work of the organs of public security.

1,4-Benzodiazepine N-nitrosoamidines have been used as scaffolds for the preparation of different tricyclic derivatives. Replacement of the N-nitrosoamidine moiety through treatment with the nucleophiles acetylhydrazine, aminoacetaldehyde dimethylacetal and 1-amino-2-propanol, followed by an acid-catalyzed cyclization step, afforded triazolo and imidazobenzodiazepines 1, 6, and 7, respectively, in good yields. When acetylhydrazine is used as a nucleophile, the overall process provides an alternative route to alprazolam (1b) and triazolam (1c), respectively.

Methods and compositions are disclosed employing combinations of antihistamines with certain diaryl tetrahydrofuran, diaryl tetrahydrothiophene, triazolobenzodiazepine or thienotriazolodiazepine PAF--antagonist compounds in the treatment of allergic reactions.

6-Phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines of the formula (IV): SPC1 wherein R is selected from the group consisting of hydrogen, alkyl of 1 to 3 carbon atoms, inclusive, phenyl, benzyl and -COOR' in which R' is alkyl of 1 to 4 carbon atoms, inclusive; wherein R1 is selected from the group consisting of hydrogen and alkyl of 1 to 3 carbon atoms, inclusive; and wherein R2, R3, R4 and R5 are selected from the group consisting of hydrogen, alkyl of 1 to 3 carbon atoms, inclusive, halogen, nitro, cyano, trifluoromethyl, and alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoylamino and dialkylamino in which the carbon chain moieties are of 1 to 3 carbon atoms, inclusive, are produced by condensing a 1,3-dihydro-5-phenyl-2H-1,4-benzodiazepine-2-thione of the formula (I): SPC2 wherein R1, R2, R3, R4 and R5 are defined as above, with an organic acid hydrazide of the formula: EQU1 wherein R is defined as above. The new products of formula IV including their pharmacologically acceptable acid addition salts are useful as sedatives, tranquilizers and muscle relaxants in mammals and birds.

An animal feed comprising a compound of the group consisting of 6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines of the formula: STR1 WHEREIN R is selected from the group consisting of hydrogen, alkyl of 1 to 3 carbon atoms, inclusive, phenyl, benzyl and -COOR' in which R' is alkyl of 1 to 4 carbon atoms, inclusive; wherein R1 is selected from the group consisting of hydrogen and alkyl of 1 to 3 carbon atoms, inclusive; and wherein R2, R3, R4 and R5 are selected from the group consisting of hydrogen, alkyl of 1 to 3 carbon atoms, inclusive, halogen, nitro, cyano, trifluoromethyl, and alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoylamino and dialkylamino in which the carbon chain moieties are of 1 to 3 carbon atom, inclusive and their pharmacologically acceptable acid addition salts in combination with a nutrient feed. A process for obtaining increased productivity in meat producing, milk producing, and egg laying animals by feeding the aforementioned compounds in combination with nutrient feeds.

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