Diazepinone

The dipolar cycloaddition of 2-diazopropane to l-methyl-3-phenylpyridazin-6(l//)-one takes place through an unstable adduct which thermally decomposes to a 1,2-diazepinone, a pyridazinone and diazanorcaradiene derivative (Scheme 46). 

The pyrazole analogues of anthranilic acids or anthranilonitriles are a convenient source of [5.6] fused systems (for a general review see (80T2359)). Thus 5-amino-4-cyanopyrazoles (in some examples an ester or a hydrazido group replaced the cyano group) have been transformed into pyrazolo[3,4-d]pyrimidines (552) and into pyrazolo[2,3-e]diazepinones (553), and 4-amino-5-methoxycarbonylpyrazoles have been converted into pyrazolo[4,3-d]pyrimidines (554). 

Pyrazolo[3,4-d][l,2]diazepines synthesis, 7, 597 Pyrazolop, 4- 6][ 1,4]diazepines synthesis, 5, 272 Pyrazolo[l, 4]diazepinones as anticonvulsant, 1, 170 Pyrazolo[2,3-e]diazepinones synthesis, 5, 272 1 H-Pyrazolo[l,5-6]imidazoles synthesis, 6, 992 Pyrazolo[2,3-a]imidazoles biological activity, 6, 1024 Pyrazolo[2,3-c]imidazoles reactions, 6, 1041 synthesis, 6, 1047 Pyrazolo[2,3-imidazoles synthesis, 6, 991 Pyrazolo[3,2- njisoquinolines synthesis, 5, 339 Pyrazolop, 4-c]isoquinolines synthesis, 5, 273 Pyrazolonaphthyri dines synthesis, 5, 339 Pyrazolone, diazophotolysis, 5, 252 Pyrazolone, 4,4-dihalo-rearrangements, 5, 250 Pyrazolone, ethoxy-hydrazinolysis, 5, 253 Pyrazolone, 4-halo-... 

Thieno[ 1,2,3]diazaborines, dihydro-bromination, 1, 656 deuteration, 1, 658 iodination, 1, 656 nitration, 1, 656 nucleophilic substitution copper-promoted, 1, 658 Thienodiazepines synthesis, 7, 595 Thieno[ 1,2]diazepines synthesis, 7, 598 Thieno[2,3-d][l, 2]diazepines synthesis, 4, 749 Thieno[3,2-d][l,2]diazepines synthesis, 4, 749 Thieno[ 1,3]diazepines synthesis, 7, 607 Thieno[ 1,4]diazepinones as anticonvulsants, 1, 170 Thieno[3,4-d][l,3]dioxol-2-one, 4,6-diphenyl-... 

Fryer et al. have found that hcnzodiazepinones rearrange to isoindoles in high yield under a variety of conditions. The benzo-diazepinone (73), on treatment vuth sodium hydride in dimethyl formamide (DMF), gave the isoindolecarboxamide (74) in better than... 

Benzodiazepinones also undergo rearrangement to isoindoles when treated with acetic anhydride and pyridine (Py). The diazepinone (81), for instance, gives l-phenyl-3-acetylisoindole (82) under these conditions. The structure of the product was established in this case by comparison with (82) prepared by acetylation of 1-phenyl-isoindole. The rearrangement may be formally represented by a... 

A more recent derivative with activities typical of the class is nitrazepam (21). Reaction of 2-amino-5-nitrobenzophe-none (19) with bromoacetylbromide affords the amide, 20. Ring closure in liquid ammonia gives nitrazepam (21). More simply, diazepinone, 22, can be nitrated directly at the more reactive C7 position with potassium nitrate in sulfuric acid. 

Nitrokerene dithiodceral reacts with anthrarulic esters to afford quinolone derivatives, which are converted into diazepinones by reductive cyclizadon The review by Kolb cavers synthetic apphcadon of nitroketene chthioacetM for heterocychc compounds Csee Scheme 10 26 ... 

An ice-cold solution of diazepinone 5a (1.76 g, 8.8 mmol) in 10% aq K.OH (10 mL, 18 mmol) was treated dropwisc with a solution of dimethyl sulfate (1.4 mL, 11.2 mmol) in MeOH (2mL), whereupon a red solid was precipitated. H20 (10mL) was added and the solid was filtered off, washed with 10% aq MeOH and suspended in MeOH (10 mL). 2M HC1 (15 mL) was added slowly, whereupon the solid dissolved and presently orange crystals of l,5-dimethyl-4-phenyl-l//-1,2-diazepin-6(7//)-one (12) appeared. H20 (10mL) was added and the product was collected yield 0.74g (39%) mp 71-72 C. The filtrate was made alkaline by slowly adding 40% K.OH, whereupon the betaine 13 separated yield 0.76 g (41 %) red plates mp 90-91 C (Et20). 

On irradiation the diazepinone 7 rearranges to the bicyclic ketone 8 by a symmetry allowed disrotatory 4rc-electrocyclization.9 5... 

Irradiation of an aqueous solution of 2-azido-1-ethylpyridinium tetrafluoroborate (3) results in the formation of diazepinone 4.156... 

Successive treatment of the diazepinone 8 with triethyloxonium tetrafluoroborate and sodium hydrogen carbonate results in ethyl 5-ethoxy-l/f-l,4-diazepine-l-carboxylate (9).31... 

A solution of the diazepinone 8 (O.lOOg, 0.55 mmol) and triethyloxonium tetrafluoroborate (0.157 g, 0.83 mmol) in CH2C12 (10 mL) was stirred for 3h at 0 C and CH2C12 (50 mL) was then added. The solution was treated with sat. aq NaHC03, followed by brine, and the organic phase was separated, dried and evaporated to give the product yield 0.093 g (86%) yellow crystals (i-Pr20/hexane) mp 36.5-37 C. 

A three-stage procedure is more versatile and gives higher yields. In this method (Method B), the 2-aminobenzophenone is treated with an a-haloacetyl halide and the resulting haloacetamide 5 converted into an aminoacetamide 6 by reaction with ammonia. Cyclization to the benzo-diazepinone 7 occurrs readily. In some cases the intermediates 5 and 6 are not isolated selected examples are given.193 94... 

The 7-bromo-5-(2-pyridyl)diazepinone 18 reacts with lead(IV) acetate to yield the 3-acetoxy derivative 19, which is converted into the 3-hydroxy compound 20 by the action of sodium methoxide, followed by water.201... 

Cyclopropyl-l,5-benzodiazepin-2-ones 4 are converted into 3-chloro derivatives 5 by the action of, V-chlorosuccinimide in contrast, A-bromosuccinimide provides 4-(l -bromoallyl)bcnzo-diazepinones 6 with opening of the cyclopropane ring.269... 

Pyrido- and pyrimido[l, 4]diazepinones have been produced by condensing pyridinediamines and a pyrimidinediamine with esters of /i-oxo acids. Because of the unsymmetrical structures of the diamines the reactions may take two courses, as exemplified by the action of ethyl acetoacetate on pyridine-2,3-diamine.308... 

Two isomeric pyrimido[4,5-6]diazepinones, 13 and 15, are obtained from pyrimidine-4,5-diamine and ethyl acetoacetate.297 Compound 13 is obtained by direct condensation of the components. 

Cyclic ureas incorporating a 1,3-diazepinone skeleton continue to be of pharmacological interest. The Ai V-disubstituted system 89 has been prepared and shown to be a potent inhibitor of factor Xa in vitro and to have an improved pharmacokinetic profile in the rabbit. The binding model for this series of compounds was confirmed by an X-ray crystallographic analysis of one analogue in the series <00BMCL301>. 

The pyridyl substituted 1,4-diazepinone derivative 91 was prepared by photolysis of 2,6-bispyridyl-4-azidopyridine, and it represents a new class of ligand for metal ion complexing <00HCA384>. 

Treatment of carboxyaldehydes 252 with hydrazine hydrate in ethanolic KOH under refluxing conditions provides an easy entry to the novel imidazo[2,l-4][l,3]thiazole fused diazepinones 253 via lactone ring opening by intramolecular nucleophilic attack of the amino group of the intermediate hydrazone which could not be isolated (Equation 31) <2006TL2811>. 

The pyrrole derivative of carbonyl azide 206 undergoes thermal Curtius rearrangement into isocyanate, which spontaneously cyclizes into pyrrolo-diazepinone 207 (Equation (27) (1991JHC1911)). 

A two-step route to tetrahydrobenzo[b]pyrrolo[3,4-e][l,4]diazepinone 241 (X = NH) starting from 4-hydroxy pyrrolone 240 has been reported (Scheme 51 (1991KFZ16)). 

Debenzylation on the side-chain with TMSl to produce substituted benzo[/]pyrrolo[l,2-d][l,4]diazepinone 181 has been reported (Scheme 36, Section 3.1.1.1 a992BMCL1639)). 

A ring-expansion process was used to produce efficiently diazepinone 392 and homopiperazine 393 from commercially available 4-piperidone 391 (equation 158). 

New seven-membered diazepinone alkoxyamines 394 for nitroxide-mediated radical polymerization were prepared through the Beckmann rearrangement (equation 159). 

The large increase in potency that is obtained by fusing an additional heterocychc ring onto the seven-membered ring of benzodiazepines is observed as well in the heterodiazepines. The required diazepinone (67-2) is prepared from the thiopheno-phenone (67-1) by exactly the same sequence as that used above. Construction of the fused triazole ring follows the method used for triazolam (Chapter 12). The... 

W2S+W2S] Electrocylizations have been effected for all the fully unsaturated isomers as shown overleaf and for some dihydro derivatives, diazepinones and fused systems (76H(4)1509, 80JCS(P1)1230, 80JCS(Pl)17l8, 76JCS(Pl)362). In some cases such reactions are followed by spontaneous extrusion of the two-atom bridge thus 5H- 1,2-benzodiazepines (88) are... 

---