Pyrazolo triazine

Diazo-5-phenylpyrazole with acetylene dicarboxylates gives the pyrazolo-triazine 266, and with acrylonitrile and ethyl acrylate it affords the dihydroderivatives 267 [77JHC227 78ZN(B)216]. Similar behavior was observed in the case of the 3-diazoindazoles that led to the indazolo-triazine derivatives (type 266) in high yields (78CB2258). 

In the reactions with phosphonio-a-methoxycarbonyl-alkanides, the products of type 261 derived from 1,3-cycloaddition can rearrange to the tautomeric lif-pyrazolo-triazole (87MI2). The reaction of 3-diazopyra-zoles and 3-diazoindazole with acyl-substituted phosphonium ylides led to pyrazolo-triazine and indazolo-triazine derivatives 266 instead of the expected triazole compounds (8IJHC675). In this case, the ylides, which can exist as phosphonium enolates, possess nucleophilic and electrophilic centers in a /8-relationship, giving [7 + 2] or [11 -I- 2]cycloaddition reactions. With dimethylsulfonio-a-aroyl-methanides, very complex, temperature-dependent mixtures were obtained, in some cases with sulfur retention (87MI3). 

Nucleophilic attack at substituted ring carbon is probably the most common reaction of 1,3,4-oxadiazoles. However, few examples have been reported of nucleophilic attack at unsubstituted carbon since such compounds (19a) are relatively uncommon. The mechanism of the well-known conversion of 2-amino-oxadiazoles (in aqueous alkali) into triazoles has been studied in the case of the reaction where (19a R = NHPh) is converted to (20). This proceeds via the anion of semi-carbazide PhNHCONHNHCHO and is initiated by hydroxide attack at C-5 <84JCS(P2)537>. A similar nucleophilic attack by hydroxide on oxadiazole (19a R = 5-pyrazolyl) was followed by cyclization to the pyrazolo-triazine (21). Hydrolytic cleavage of 2-ary 1-1,3,4-oxadiazoles to aroyl-hydrazides allows use of the former as protected hydrazides. Oxadiazole (19a R = 4-... 

Amino-A -(3-methyl-5-isoxazolyl)benzensulfonamide was converted into pytazole and pyrazolo-triazine and -pyrimidine derivatives 611, having antimicrobial activity <2002AC0159>. 

Imidazo[4,5-c]pyrazole 4-oxides (762 R = p-N02CeH4) are obtained by base-catalysed cyclisation of the nitro-pyrazoles (761).Cyclisation of the pyrazolylhydrazone (763) gives either the pyrazolo-triazole (764) or the pyrazolo-triazine (765), depending on conditions. ... 

Figure 5.6 Polaris s macrocyclic CK2 inhibitors derived from pyrazolo-triazines.

Pyrazolo[3,4-d]pyridazines (555) can be prepared readily from hydrazines and pyrazoles substituted in positions 4 and 5 with an acyl and an ester group, or with two ester groups. 4,5-Pyrazolinediones have been used as starting materials for the synthesis of the quinoxaline derivatives (548) (see above) and of pyrazolo[3,4-e][l,2,4]triazines (556)... 

A heterocyclization involving the N-2 atom of indazole affords [l,2,4]triazino[4,5-h]-indazoles (561) from the 3-carbohydrazinoindazole (78JHC1159,79JHC53). The corresponding pyrazolo[l,5-tf][l,2,4]triazine (562) has been prepared by the same procedure (8UHC1319). 

Reactions of 3-hydrazino-l,2,4-triazine 1-oxide 31 or 3-hydrazinopyrido [2,3-c]-l,2,4-triazine 1-oxide 32 with diethoxymethyl acetate or triethyl orthoformate proceed as cyclization reactions at the N(4) atom and the amino group to form the corresponding pyrazolo[3,4-c]-l,2,4-triazine 6-oxides 33 and 34 (74MI, 80JOC5421, 80MI). 

Chemical Name 5-(dimethylamino)-9-methyl-2-propyl-1 H-pyrazolo [ 1,2-a] [ 1,2,4] benzo-triazine-1,3(2H)-dione... 

Cyclization of hydrazones 318 gave [75CR(C)14I9] pyrazolo[l,5-J][I,2,4]triazine 319 (Scheme 67). 

The reaction of dimethyl-1,2,4,5-tetrazine-3,6-dicarboxylate 353 with aromatic amines gave (82CB683) pyrazolo[3,4-e][l,2,4]triazines 354 (Scheme 75). 

Treatment of 5-(dichlorophenylmethyl)-3-phenyl[ 1,2,4]triazin-6( 1H)-one 357 or the respective ketone with hydrazine or phenylhydrazine gave 358, which were cyclized with acetic acid to pyrazolo[4,3-c][ 1,2,4]triazines 359 (84PHA504 85MI2) (Scheme 77). 

Pyrazolo[4,3-e][l, 2,4][triazines 365 were prepared (80JHC209) by treatment of 4-bromo-3-phenylpyrazol-5-ylhydrazonyl chlorides 364, obtained from 363, with hydrazine or phenylhydrazine. It should be noted that the reaction of 3-phenylpyrazol-5-ylhydrazonyl chloride gave (77JHC227) pyrazolo[l,5-c][l,2,4]triazine (Scheme 79). 

Pyrimido[5, 4 4,5]pyrazolo[3,2-c][l,2,4]triazine derivatives 1049and 1050 were prepared by treatment of diazo compound 1048, prepared from 1047, with pentane-2,4-dione and ethyl acetoacetate, respectively [92JCS(Pl)239]. 

Bromination of pyrazolo[2,3-c][l,2,4]triazines (179) occurred only in the pyrazole ring (83AP697). 

Imidazo[4,S-J]l,2,3-triazines and pyrazolo[3,4-Similar reactions have been used to obtain imidazopytidazines <95JHC1417, 1423 >. 

Novel thieno[2,3 3,4]pyrazolo[l,5-a]pyrimidines and triazines 58 can be prepared by reacting the thienopyrazoles 57 with 1,3-biselectrophiles <95MI02 96CA(124)176031>. 

A development of the reaction described above for the synthesis of pyrrolo[2,l- [l,2,4]triazines using l-aminopyrrole-2-carbonitrile and N,N-dimethyldichloromethyl-iminium chloride utilising ethyl 4-amino-3-cyanopyrazolo[5,1 -c] [ 1,2,4]triazine-8-caiboxylate 60 yields pyrazolo[5,l-c]pyrinudo[4,5-e][l,2,4]triazines 61 <96T3037>. 

The inverse electron demand reactions of 2,4,6-tris(ethoxycarbonyl)-1,3,5-triazine and 5-aminopyrazoles to provide a one-step synthesis of pyrazolo[3,4-. 

Phenyl-l,2,4-triazine 4-oxide 91 reacts with l,3-dimethyluracil-6-hydrazones 92 in DMF in the presence of triethylamine to give pyrazolo[3,4-. 

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