Pyrazolo indoles

A derivative of 163, 3-(2-morpholinoethylthio)[l,2,4]triazino[5,6-fo]indole dihydrochloride, is used as a thrombolytic (91URP1672373). Derivatives of the pyrazolo[5,l-c][l, 2,4]tria-zines were used as a constituent of silver halide color photographic supported material, which showed good color reproducibility [91JAP(K)03/291649]. The protective action of [l,2,4]triazino[4,3-a]benzimidazoles as corrosion inhibitors was studied (91MI8). 

Variation of the ring portion of acyclovir has been achieved. Compounds include monocyclic (isocytosine, triazole, imidazole), bicyclic (adenine, 8-azapurine, pyrrolo[2,3-c/]-pyrimidine, pyrazolo[3,4-[Pg.131]

Ir a similar reaction, Ruccia et al.109 obtained adducts 104 when substituted indoles were treated with nitrilimines. Two of these adducts were readily dehydrogenated with chloranil in xylene to give the pyrazolo[3,4-ft]indoles (105). 

Other ring contractions that give azapentalene derivatives include the rearrangement of a fused oxazine to a pyrazolo[l,5-a]indol-4-one with acetic anhydride,165 and an interesting photochemical contraction of a cyclic lactone, which produces an isomeric fused indolone by a mechanism thought to involve the first meta photo-Fries rearrangement [Eq. (19)].166 The product was used as an intermediate for the synthesis of mitomycin antibiotics (Section VI,A). 

Ji and co-workers [73] have elaborated a simple and efficient approach for the synthesis of highly functionalized pyridines 24 via a one-pot, three-component reaction under microwave irradiation. This method enables the incorporation of a pyrazolo[3,4-h]pyridine and an indole moiety into the same molecule. The synthesis was achieved by reaction of a suitable aldehyde and 3-cyanoacetyl indole with 5-aminopyrazol. Particularly valuable features of this method include high yields, broad substrate scope, and short reaction times. It has been observed that when there are electron-withdrawing groups on the aryl aldehyde this results in a faster and higher yielding reaction (Scheme 21). 

Diazotization of 4-amino-5-alkynylpyrazole 335 followed by intramolecular cyclization gave 7-chloro-17/-pyr-azolo[4,3-f]pyridazines 336 the amino and alkynyl positional isomers at the C-3 and C-4 positions were also cyclized to give other pyrazolopyridazines (Equation 64) <1998F1C0519>. Diazotization of 4-aryl-5-aminopyrazoles (aryl = 4,5-dimethoxyphenyl and indol-3-yl) followed by intramolecular azo coupling reactions led to the corresponding pyrazolo[3,4-f]cinnolines or pyrazolo[3, 4 6,5]pyridazino[3,4-. ]indoles <2004CHE1506>. 

Progress has been made in the experimental procedures for the formylation of pyrazoles (Vilsmeir-Haack reaction) at their 4 position <93JHC957, 94CPB237). For instance, 4/f-pyrazolo[l,5-a]indoles are formylated under milder eonditions than pyrazoles <94CPB237>. 

Derivatives of pyrazolo[l,2-a]benzo[l,2,3,4]tetrazin-5-ones 66 designed as novel alkylating agents have been synthesized and showed antiproliferative activity <05JMC2859>. Reactions of 2-diazoindoles with alkyl or aryl isocyanates afforded derivatives of the new ring system [l,2,3,5]tetrazino[5,4-a]indole 67, some of which showed antiproliferative activity <05BMC295>... 

Aza-indoles can be prepared from 2,6-dichloropyridin-3-yl-epoxides by reaction with primary amines " and 5-, 6-, and 7-azaindole-2-esters can be made" via the Hemetsberger-Knittel route. Note that 4-aza-indoles cannot be made this way since cyclisation of the appropriate precursor takes place preferentially onto the ring nitrogen generating a pyrazolo[l,5-fl]-pyridine. 

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