Dibenzo-1,4-diazepines

Amides [41,44], thioamides [41 ] and amidines [45] are converted into nitriles by the reaction with dichlorocarbenes generated by Makosza s procedure (Table 7.16). Under similar conditions, monosubstituted and A.A-disubstituted ureas are converted into cyanamides (Table 7.17) JV,(V -disubstituted ureas produce carbodi-imides in low yield [41,46,47]. /V-Carbamoyl derivatives of dibenzo[/ /]diazepines and the related 10, l l-oxirane derivatives are converted into the corresponding... 

Diazepinomicin (ECO-4601) (191) Dibenzo- diazepine alkaloid Diazepinomicin (ECO-4601) (191) Oncology RAS-mitogen-activated phosphokinase (MAPK) pathway inhibitor and inhibition of tiie peripheral benzodiazepine receptor Phase I/II Thallion (Ecopia) 906-910... 

Benzo- as well as heteroaromatic systems were obtained allowing for a variable substitution pattern in the benzoazepine frameworks. To access the dibenzo-diazepine or dibenzoxazepinone frameworks according to C-N cross-coupling methodology, a different strategy had to be pursued. The introduction of the nitrogen atom or the amide functionaHty was accompHshed by the condensation of ammonia with keto- or ester-carbonyl frmctionaHties (Scheme 13.96 and Scheme 13.97) [142],... 

H-Dibenzo[d,/][l,3]diazepine, 5,7-dihydroxy-synthesis, 7, 605 Dibenzodiazepines synthesis, 7, 605... 

Chemical Name 8-chloro-1 1-(4-methyl-1-piperazinyl)-5H-dibenzo[b,el [1,4] diazepine Common Name —... 

Chemical Name 10-[2-(dimethylamino)ethyl] -5,10-dihydro-5-methyl-11H-dibenzo[b,ej-[1,4] diazepin-11-one hydrocliloride... 

Methyl-11 -hydroxy-5H-dibenzo[b,e] [1,4] -diazepine Sodium amide... 

The reaction was carried out in THK b Two mol equiv of LiAlH4 were employed. 3,8-Dichloro-llff-dibenzo[c,/]]l,2 diazepine (2c) Typical Procedure 149... 

Diverse derivatives 5 (X = F or N02) of diphenyldiazene have similarly been converted into ll/7-dibenzo[c,/][l,2]diazepines 6 in refluxing 1,2-dichlorobenzene with the elimination of hydrogen fluoride or nitrous acid, respectively.150... 

Dibenzo[l, 2]diazepines are oxygenated to /V-oxides by peracetic acid e.g. formation of 2 from... 

Dibenzo[c /][l, 3]diazepines 5 or 6 bearing an amino or substituted amino group in position 6 are obtained from biphenyl-2,2 -diamine and 2-methylisothiourea sulfate or ALAAdiisoprop-ylcarbodiimide, respectively.175... 

Dibenzo[l,3]diazepines 9, together with amidines and benzimidazoles, are produced by a rearrangement reaction when certain A.A -diarylamide oximes 7 are treated with tosyl chloride. The intermediate 0-tosyl derivatives 8 cannot be isolated.176... 

The formation of 5//-dibenzo[r/,/][l,3]diazepin-6(7//)-one (13, R = H) in good yield by fusing biphenyl-2,2 -diamine with urea was reported in 1901177 and has since been extended to the preparation of numerous analogs.178 Selected examples are given yields were generally not reported.177-179... 

The (mcthylsulfanyl)dibenzodiazepine 19 reacts with the hydrochlorides of primary or secondary amines to yield, after basification, 5/f-dibenzo[c ,/][l, 3]diazepin-6-amines 20.175... 

The reduction of a dinitro ketone to an azo ketone is best achieved with glucose. 2,2 -Dinitrobenzophenone treated with glucose in methanolic sodium hydroxide at 60° afforded 82% of dibenzo[c,f [i 2]diazepin-l 1-one whereas lithium aluminum hydride yielded 24% of bis(o-nitrophenyl)methanol [575], Conversion of aromatic nitro ketones with a nitro group in the ring into amino ketones has been achieved by means of stannous chloride, which reduced 4-chloro-3-nitroacetophenone to 3-amino-4-chloroacetophenone in 91% yield [178]. A more dependable reagent for this purpose proved to be iron which, in acidic medium, reduced m-nitroacetophenone to m-aminoacetophenone in 80% yield and o-nitrobenzophenone to o-aminobenzophenone in 89% yield (stannous chloride was unsuccessful in the latter case) [903]. Iron has also been used for the reduction of o-nitrochalcone, 3-(o-nitrophenyl)-l-phenyl-2-propen-l-one, to 3-(o-aminophenyl)-l-phenyl-2-propen-l-one in 80% yield [555]. 

The other way of synthesis of clozapine is from 8-chloro-10,ll-dihydro-5H-dibenzo[b,e]l, 4-diazepin-ll-thione, which is alkylated at the sulfur atom of the dibenzodiazepine ring by 4-nitrobenzylchloride in the presence of potassium fert-butoxide, giving iV-methyl derivative (6.5.8). Reaction of this with A-methylpiperazine gives the desired clozapine (6.5.7) [59]. 

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