Imidazo triazepines

Resin bound dipeptides have been used in the parallel synthesis of 3,4,7-trisubstituted 4,5,8,9-tetrahydro-3//-imidazo l, 2-a l, 3,5 triazcpinc-2(7//)-thioncs and Af-alkyl-4,5,7,8-tetrahydro-3//-imidazo[ 1,2-a][l, 3,5]triazepin-2-amines by ring construction methodology <06JCOl27>. 

Treatment of imidazo[2,l-A [l,3,5]benzotriazepines 79 with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) in acetonitrile at ambient temperature resulted in oxidative ring contraction with formation of stable (dihydroimidazo-lybbenzimidazoles 80 (Scheme 15). The reaction was suggested to occur via the initial hydride abstraction from N(6) followed by triazepine ring scission and formation of nitrenium ion <2005FA127>. 

The imidazo[4,5- ]triazepines 529 were synthesized in a single-pot reaction of 4-amino-l-benzylimidazole-5-carbal-dehyde 528 with 1,2-dimethylhydrazine dihydrochloride and trimethyl or triethyl orthoformate using the corresponding alcohol as the solvent (Scheme 271) <2004JME1044, 2004NN263, CHEC-III(13.14.7T1)419>. 

Imidazo-fused analogues 174 of the 1,2,4-triazepine system have been synthesised from pre-formed imidazoles 173. Reaction of 173 with iV,iV -dimethylhydrazine.2HCl and the appropriate orthoformate then resulted in the triazepine derivatives 174 the formation of the imidates 175 is proposed to occur initially, followed by the ring closed intermediates 176. Reaction of 176 with the alcohol would then give 174 <04JMC1044>. 

In 2002 Raboisson et al. reported a method for synthesis of 4,7-dihydro-lH-imidazo[4,5-e]-l,2,4-triazepin-8-one derivatives by use of microwave methodology. The reaction involves aminoimidazole carboxhydrazide and ortho esters, and the subsequent alkylation of the l,2,4-triazepin-8-one obtained occurs regioselectively at Cl [120]. 

When jS-ketoesters (60) or aryl methyl ketones (63) were used instead of the 1,3-diketones (53), the 8-oxo-imidazo[l,2-Z)]-1,2,4-triazepines (61) <85KGS694> or the dihydro compounds (64) <84KGS1396> were produced from the corresponding diaminoimidazoles (59) and (62), respectively. The cyclocondensation of the diamino compounds (62) and (65) with vinyl ketones (66) also proceeded to yield the corresponding dihydroimidazo-1,2,4-triazepines (67) <83KGS93> and tetra-zolo-1,2,4-triazepines (68) <90KGS1533> respectively, in moderate yields (Scheme 9). 

The mass spectra of seven 2-thio- and four 2-oxo-l,3,4-benzotriazepines, for example (128), have been recorded and the fragmentation patterns elucidated by exact mass measurement and metastable ion analysis <90JHC259>. The x-ray crystallographic analysis of the imidazo[l,5-fe]-l,2,4-triazepine (129) showed that a double bond possesses a 1 and 2 linkage (C=N 1.276 A) with no evidence of an alternative tautomer in which the double bond is between the 2 and 3 positions (C—C 1.490 A) <93AX(C)I693>. 

---