KR830009058A - Method for preparing phenyl substituted pyrido [1,4] benzodiazepines - Google Patents

Abstract

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Description

Method for preparing phenyl substituted pyrido [1,4] benzodiazepines

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Claims (5)

Then a mixture of halo-aminopyridine of formula (IV) and (aminophenyl) arylmethanone of formula (III) is heated at 17-200 ° C. for a time shorter than the time required for ring closure to pyridobenzodiazepine and then produced. [2- (aminopyridinyl) aminophenyl] arylmethanone, separated from the starting materials and some of the ring-closed pyridobenzodiazepines, using a solvent, wherein [2-[(amino Process for the preparation of pyridinyl) aminophenyl] arylmethanone. Wherein Ar is phenyl substituted by 2,3 or 4-pyridinyl, 2 or 3 thienyl, phenyl or 1 to 3 radicals selected from halo, lower alkyl, lower alkoxy, trifluoromethyl or nitro And may be the same or different, Z is hydrogen, halogen, lower alkyl, lower alkoxy, hydroxy or nitro, Y is hydrogen or lower radical of 1 to 2 selected from lower alkyl, lower alkoxy or hydroxy and may be the same or different . The time and conditions required for the water to be removed from the reaction of a mixture of halo-aminepyridine of formula (IV) and (aminophenyl) arylmethanone of formula (III) or of formula (II) Under heating to ring to obtain the pyrido [1,4] benzodiazepine of the general formula (Ia), and to reduce the compound prepared above by sodium borocyanohydrin to yield the compound of the general formula (Ia-1) A process for the preparation of pyrido [1,4] benzodiazepines of the following general formula (I), which is obtained. Wherein Ar is substituted by 1, 3 radicals selected from 2,3, or 4-pyridinyl, 2 or 3 thienyl, phenyl or halo, lower alkyl, lower alkoxy, trifluoromethyl or nitro Phenyl and may be the same or different, Z is hydrogen, halogen, lower alkyl, lower alkoxy, hydroxy or nitro, Y is hydrogen or lower radical of 1 to 2 selected from lower alkyl, lower alkoxy or hydroxy and may be the same or different have. The method of claim 2 wherein the temperature is 170 to 200 ° C. 4. The method of claim 2 wherein the water is removed under reflux in an aprotic solvent. 1) the time required for water to be removed from the reaction of a mixture of halo-aminopyridine of formula (IV) and (aminophenyl) arylmethanone of formula (III), or a reaction product thereof of formula (II): And ring-closed under heating to obtain pyrido [1,4] benzodiazepine of the general formula (Ia), 2) optionally, reducing the compound prepared in step 1) with sodium borocyanohydrin to obtain the compound of formula (Ia-1) 3) The product of step 1) or 2) is subjected to halo-Alk'Q reagent, wherein Q is -N- (lower alkyl) ₂ , 1-pyrrolidinyl 1-piperidinyl, 4-substituted-piperazine- 1-day, 4-morpholino, 1-phthalimido, Lower alkyl or halo) and, if n is 0, optionally reduced to sodium borocyanohydrin to give a compound selected from the mixture having the following general formula (lb) 4) When Q is phthalimido, it is reacted with alcoholic hydrazine hydrate and acid, and when n is 0, it is optionally reduced with sodium borocyanohydrin to give the compound of formula (Ic) 5) optionally reacting the compound prepared in step 4) with triethylorthoformate for a time sufficient to form the methaneimide ester of formula (Id) and then reducing the methaneimide ester with sodium borohydride. When n is 0, it is reduced to sodium borocyanohydrin to give a compound of formula (Ie) 6) optionally, reacting the compound prepared in step 4) with ethylchloroformate (and triethylamine) followed by reduction with lithium aluminum hydride to obtain the compound of formula (Ie-1) 7) optionally a compound prepared in step 3) wherein Q is Hydrolyzing to lower alkyl to give the compound of formula (Ie-2) 8) In contrast, when Q is chloro in the compound prepared in step 3), the pyri of formula (I) is characterized in that it is reacted with dialkylamine to give a compound of formula (Ib-3) [1,4] Benzodiazepine and a method for preparing acid addition salt thereof. Wherein R is hydrogen, lower alkyl, -Alk'-NR ¹ R ² or Alk'-N = CH-OC ² H ⁵ , and R ¹ and R ² are hydrogen, lower alkyl or -C (O)- Is O-lower alkyl or R ¹ and R ² together with adjacent nitrogen atoms are 1-phthalimido, 1-pyrrolidinyl, 4-morpholino, 1-piperazino, or 4-substituted piperazine-1 -Is yl, Ar is phenyl substituted by 1 to 3 radicals selected from 2,3 or 4-pyridinyl, 2 or 3-thienyl, phenyl or halo, lower alkyl, lower alkoxy, trifluoromethyl or nitro And may be the same or different, Alk 'is a straight or branched chain hydrocarbon having 1 to 8 carbon atoms, Z is hydrogen, halogen, lower alkyl, lower alkoxy, hydroxy or nitro, Y is hydrogen or lower alkyl, lower alkoxy or hydroxy 1 to 2 radicals selected from Roxy and may be the same or different, where n is 0 and 1, and when n is 0 the dotted line is a double bond. ※ Note: The disclosure is based on the initial application.