Pyrrolo triazines

The Mitsunobu reaction was applied to the synthesis of pyrrolo[l,2-d [, 2,4]triazines from pyrrole derivative 71. Thus reduction of 71 gave alcohol 72, which on treatment with diethylazodicarboxylate and triphenyl phosphine gave 74 via the open chain intermediate 73. Hydrolysis of 74 gave 75 (84AG517) (Scheme 18). 

Pyrrolo annulated triazine 77 was prepared (88TL4415) by the [6 + 4]-cycloaddition of azoniafulvene ion 76 with azomethine imines generated from benzylidene phenylhydrazone (Scheme 19). 

The synthesis of this ring system was achieved by the reaction of the ketene aminal 79 with 3-morpholino-l-ethyl-l,2,4-triazinium tetrafluoro-borate 78 to give 80 (89IZV494). Cyclization of 78 with the bifunctional nucleophile 81 gave the pyrrolo[3,2-e][l,2,4]triazinones 82 (88TL1431). This reaction represents the first example of orthocyclization onto the 1,2,4-triazine ring by the addition of dienophiles at C-5,6 (Scheme 20). 

Treatment of 1,2,4-triazines 91a-91e with the electron-deficient die-nophile dimethyl acetylenedicarboxylate gave products, depending on the substituents [77LA( 10) 1718]. Pyrrolo-[2, -/][ ,2,4]triazines 92 were obtained via [4 + 2]-cycloaddition [77LA(9)1413, 77LA( 10)1718] with 91, but interaction with 91b in the absence of solvent gave, in addition to 92, the pyrido[2,l-/][l,2,4]triazine 93 and [l,3]oxazino[2,3-/][l,2,4]-triazine 94. In case of 91a pyridine and benzene derivatives were also formed in addition to 92 (Scheme 23). 

Several new 2,4-disubstituted pyrrolo[2,l- [l,2,4]triazines, which can be further elaborated, and pyrrolo[5,1 -c]pyrimido[4,5-e] [ 1,2,4]triazines have been made by the reaction of iV,Af-dimethyl-dichloromethyleniminium chloride with l-aminopyrrole-2-carbonitrile and ethyl 4-aniino-3-cyanopyrazolo 5,l-c][l,2,4]triazine-8-carboxylate respectively (Scheme 7) <9613037 >. 

Furo[2, 3 4,5]pyrrolo[l,2-d][l,2,4]triazolo[3,4-/][l,2,4]triazines 667 were prepared by reaction of 664 with phosphorus pentasulfide to give 665 followed by conversion to the hydrazino derivative 666 and subsequent cyclization with ortho-esters (84CCC65, 84M13). Similarly, the indolo analogue 670 was prepared from 668 by sulfurization and hydrazinolysis to give 669, which cyclized with ortho-esters (84CCC1529). 

The synthesis of pyrazolo[4,3-rf]-l,2,3-triazine starting from a pyrazolo-3-carbaldehyde derivative has been reported <00JIC168>. Azolo-l,2,4-triazine derivatives have been prepared via the reaction of functionalized thiazole derivatives with several heterocyclic diazonium salts <00JCR(S)206>. The reaction of 1,2,4-triazolium salt 67 with alkene 68 gives the pyrrolo[2,l-/][l,2,4]triazine 69 <00H(53)213>. 

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