37115-32-5Relevant academic research and scientific papers
Mannich Reactions of Heterocycles with Dimethyl(methylene) Ammonium Chloride: A High Yield, One-step Conversion of Estazolam to Adinazolam
Gall, Martin,Kamdar, Bharat V.,Lipton, Michael F.,Chidester, Connie G.,DuChamp, David J.
, p. 1649 - 1661 (2007/10/02)
The readily prepared ammonium salt, (CH3)2N=CH2(1+)*Cl(1-), 4, functionalized heterocycles differently, but in a predictable fashion, under neutral, basic or acidic conditions.Triazolo- and imidazobenzophenones 1b' and 5, which primarily underwent intramolecular isomerization to indolols 2a' and 6a rather than intermolecular electrophilic substitution under conditions of the normal aqueous Mannich reaction, were converted with 4 to the desired benzophenone derivatives, 1c' and 7, respectively, in moderate yields.The 1-unsubstituted triazolo- or imidazobenzodiazepines, 10a estazolam and 10b, were transformed to the corresponding 1-(dimethylamino)methyl derivatives, 11a (adinazolam) and 11b, in good to moderate yields (61percent and 32percent, respectively.) Under acidic reaction conditions, 1-methyl triazolobenzodiazepine, 10d (alprazolam), afforded 12e, the product of attack at C-4 of the triazolobenzodiazepine ring system.Under strongly basic conditions in which the anion of 10d was generated prior to reaction with 4, both 12e and its isomer, 15, were formed.These results complement the report that 4 may be used to functionalize the 1-methyl position of triazolobenzodiazepines, and further demonstrate the versatility of reagent 4 in heterocyclic synthesis.
Process to prepare α-chloroalprazolam
-
, (2008/06/13)
α-Halomethylbenzodiazepines (II) are produced by direct halogenation of methylbenzodiazepines (I) using sulfuryl halide.
Novel synthesis of the pharmacologically important 1-substituted-6-phenyl-4H-s-triazolo[4,3-α][1,4]benzodiazepines
Hester Jr.
, p. 575 - 581 (2007/10/02)
Several 6-phenyl-4H-s-triazolo[4,3-α][1,4]benzodiazepines have useful biological activity both in experimental animals and in man. This manuscript describes a novel synthesis of these compounds from intermediates that do not have a pre-formed benzodiazepine ring system.
1-(Aminoalkyl)-6-aryl;-4H-s-triazole[4,3-a][1,4]benzodiazepines with antianxiety and antidepressant activity
Hester Jr.,Rudzik,Von Voigtlander
, p. 392 - 402 (2007/10/02)
A series of 1-(Aminoalkyl)-6-aryl;-4H-s-triazole[4,3-a][1,4]benzodiazepines has been prepared and evaluated for central nervous system activity. The authors have found that members of this series have activity in pharmacological test systems designed to detect both anxiolytic and antidepressant activity. Each type of activity could be varied independently by appropriate substituent selections.
Process for the production of 1-[(dimethylamino)methyl]-6-phenyl-4H-triazolo[4,3-a][1,4]-benzodiazepine
-
, (2008/06/13)
A process for the preparation of 1-[(dimethylamino)methyl]-6-substituted-4H-s-triazolo[4,3-a][1,4]benzodiazepine which comprises the reaction of a 4H-s-triazolo[4,3-a][1,4]benzodiazepine with the reagent STR1 wherein X- signifies the anion of a monovalent acid.
1-[(Aminooxy)-methyl]-6-substituted-4H-s-triazolo[4,3-a][1,4] benzodiazepines
-
, (2008/06/13)
Compounds of the formula: STR1 wherein R'o and R"o are hydrogen or alkyl of 1 to 3 carbon atoms, inclusive; R1 is hydrogen, fluoro, chloro, bromo, nitro, trifluoromethyl, or alkylthio in which the alkyl moiety is of 1 to 3 carbon atoms, inclusive; R2 is phenyl, o-chlorophenyl, 0-fluorophenyl, 2,6-difluorophenyl and 2-pyridyl are prepared by multistep reactions from compounds of formula I: STR2 wherein R1 and R2 are defined as above and X is chlorine or bromine. Compounds of formula III, intermediates in the preparation thereof, Schiff's bases of compounds IIIA (III in which R'o and R"o are hydrogen), and the pharmacologically acceptable acid addition salts are useful in birds and mammals, including man, as sedatives, antianxiety, antidepressant, anticonvulsive, and muscular relaxing agents.
Intermediates and process for the production of certain triazolobenzodiazepines
-
, (2008/06/13)
A multi-step process for the preparation of 1-[(amino - or substituted amino)methyl]-6-phenyl-4H-s-triazolo-[4,3-a][1,4]benzodiazepines of the formula VI: SPC1 wherein R' is hydrogen or alkyl of 1 to 3 carbon atoms, inclusive, and wherein the rings A and B are unsubstituted or substituted by one or two substituents selected from the group consisting of chloro, fluoro, bromo, nitro, and trifluoromethyl, which comprises: treating a compound of the formula I: SPC2 wherein rings A and B are defined as above, with acetic anhydride and formic acid to obtain compound II: SPC3 wherein A and B rings have the significance as above, treating compound II with sufficient formaldehyde to produce compound III, the 3,5-bis(hydroxymethyl)derivative of II; treating III with phthalimide, triphenylphosphine and diethyl azodicarboxylate to give compound IV, the 3,5-bis(phthalimidomethyl) derivative of II; and treating IV with hydrazine hydrate to obtain a compound of formula V SPC4 wherein rings A and B are defined, as herein above. Compound V can then be alkylated in known manner to give those compounds of formula VIa which corresponds to formula VI when R' is desired to be alkyl. The compounds of formula VI have antidepressant and antianxiety effects in mammals and birds.
Process for the production of 1-aminomethyl-6-phenyl-4h-s-triazolo-[4,3-a][1]benzodiazepines and intermediates
-
, (2008/06/13)
A multistep process for the production of a compound of the formula V: SPC1 wherein R' and R" are alkyl of 1 to 3 carbon atoms, inclusive or together EQU1 is pyrrolidino, piperidino, 4-methylpiperazino or morpholino; and wherein the rings A and B are unsubstituted, or substituted by one or more substituents selected from the group consisting of fluoro, chloro, bromo, nitro and trifluoromethyl, which comprises treating an equivalent of a compound of formula 1: SPC2 Wherein rings A and B are defined as above, with 2 equivalents of an α-phthalimido acetyl halide in an inert organic solvent to obtain a 1,3-dioxo-2-isoindolineacetic acid, [[N-(2-benzoylphenyl)-1,3-dioxo-2-isoindolineacetamido]methylene]hydrazide II which when treated with trifluoroacetic acid gives compound III; treating compound III with a dialkylmethyleneammonium chloride in an inert organic solvent to obtain a 2-[3-(dialkylamino)methyl-5-(phthalimidomethyl)-4H-1,2,4-triazol-4-yl]benzophenone IV and treating IV with hydrazine in an alkanol to obtain a compound V above. Also claimed are the intermediates II and IV. The 1-aminomethyltriazolobenzodiazepine compounds (V) are used for treatment of anxieties and/or depressions in mammals and birds.
