Pyrrolo triazin-6-ones

Table 2 Betaine synthesis via alkylation of pyrrolo[1,2-d][1,2,4]triazin-4-one 27...

Highly substituted pyrrolo[l,2- ][l,2,4]triazines were synthesized from pyrrole derivatives, by closure of the triazine ring. Thus, hydrolytic cleavage of some 1,2-diaminopyrroles having a 1-NH-BOC-protected amino function 43 followed by reaction with 1,2-dicarbonyl compounds afforded a one-pot access to the corresponding bicyclic heterocycles 44 (BOC = f-butoxycarbonyl Equation 6) < 1997J(P 1)1829>. 

Dehydrative condensation of pyrrole-2-carboxaldehyde 77 and ethyl carbazate afforded carbethoxyhydrazone 78 in quantitative yield. Cyclization of 78 in the presence of a catalytic amount of sodium hydride (10mol%) in dimethyl-formamide (DMF) at 100°C led to the formation of pyrrolo[l,2-tf][l,2,4]triazin-4-one 27 in 75% yield (Scheme 8) <1999T13703>. 

Another BMS example, shown in Scheme 11.14, uses a cumene peroxide rearrangement to prepare 6-hydroxy-5-methyl-3H-pyrrolo[2,l-f [l,2,4]triazin-4-one, an intermediate for protein kinase inhibitors (brivanib). The terhary alcohol is converted to the hydroperoxide in situ with H2O2 and reacted with aqueous meth-anesulfonic acid as a catalyst to cause rearrangement [31]. 

Two reaction centers of 477-furo[3,2-6]pyrrole-5-carboxyhydrazide (228) (Scheme 15) <84CCC65> were utilized in cyclization reactions with either triethyl orthoformate or orthoacetate, leading to furo[2, 3 4,5]pyrrolo[l,2-d][l,2,4]triazine-8(7H)-one (229). Phosphorus pentasulfide treatment of this product (229) gave the corresponding thione (230) which with hydrazine hydrate gave (231). This compound (231) with triethyl orthoformate gave furo[2, 3 4,5]pyrrolo[l,2- /][l,2,4]triazolo]3,4-/][l,2,4]triazine (232) the 3-methyl (233), 6-methyl (234) and 3,6-dimethyl (235) derivatives were also made. 

Reaction of 1,2,4-triazinium salts with amides of acetoacetic acid results in 1,4,4a,5,7,7a-hexa-hydro-6/7-pyrrolo[3,2-e]-l,2,4-triazin-6-ones via the diaddition of bifunctional nucleophiles at the C-5 and C-6 positions of the 1,2,4-triazine ring (Equation (2)) <88TL1431>. 

Cyclohepta[4,5)pyrrolo[l,2-fl]imidazoles, 2-aryl-, halogenation. 59, 283 Cyclohepta[4,5)pyrrolo[3,2-e][l,2,4]triazine, 3-chloro- 10-(4-chlorobutyD-5,6,7,8,9,10-hexahydro-, 59, 50 3//-Cyclohept(e]isoxazoles, 3a,4,5,6,7,8-hexahydro-, 60, 311-3 Cyclohex-2-en-l-ones, 2- and 3-bromo-, regioselectivity of nitrile oxide cycloaddition, 60, 304 Cyclols, piperazine-2,5-dione-related, 57, 211-7... 

The inverse electron demand Diels-Alder reactions of 5-amino-177-pyrrole-3-carbonitriles 1121 with various 1,3,5-triazines 1122 are suitable for one-pot syntheses of highly substituted and highly functionalized 7/7-pyrrolo[2,3- -pyrimidine-5-carbonitriles 1123 (Scheme 220) <2002JOC8703>. These are the central heterocyclic nuclei of various nucleoside natural products such as Toyocamycin, Sangivamycin, and Tubercidin (Figure 5). 

A new bicyclic betaine, a pyrrolo[l,2-.7 [l,2,4]triazin-2-ium -olate 1347, was prepared by the thermolysis of a ring-expansion reaction product 1346, 2,3-di(/-butyl)-l-hydroxy-2,3-dihydropyrrolo[l,2-.7 [l,2,4]triazin-4(17/)-one, of 1,2-di(/-butyl)-l,2-diaziran-3-one 1345 with 177-pyrrole-2-carbaldehyde (Scheme 256) <1995MI1>. Its cyclization reaction with a dipolarophile such as dimethyl 2-butynedioate leads to a fused ring-enlarged compound, a triazocinone derivative 1348 in rather low yield. Heating a solution of triazocine 1348 in benzene- 6 in an NMR tube at 140 °C for 0.5 h leads to its thermal transformation into compound 1349 in 21% yield via skeletal isomerization <1999T13703>. 

Dehydrative condensation of lf/-pyrrole-2-carbaldehyde and ethyl 1-hydrazinecarboxylate gives ethyl pyrrol-2-ylmethylidene)-l-hydrazinecarboxylate 1350 in quantitative yield (Scheme 257) <1999T13703>. A cycli-zation of the hydrazinecarboxylate 1350 by a stoichiometric amount of NaH was then examined, but a complicated mixture was obtained. It was found that pyrrolo[l,2-i7 [l,2,4]triazin-4(3/7)-one 1351 can be prepared by treatment of compound 1350 with a catalytic amount (0.1 equiv) of the base, in 75% yield. It is noteworthy that the liberated ethoxide ion which functioned as a base instead of NaH provided a catalytic system. 

S., Cleavage and reactions of some NH-Boc protected 1-aminopyrroles. A new one-pot route to pyrrolo[l,2-b] [l,2,4]triazines together with spectroscopic and X-ray sliidics, J. Chem. Soc., Perkin Trans. 1, 1829, 1997. 

R-Furo[2, 3 4,5]pyrrolo[l,2-if]-l,2,4-triazine-l-ones (384) by reaction with phosphorus pen-tasulfide gave thiones (385) which, by treatment with hydrazine hydrate, yielded the triazines (386). Reaction of of the latter compounds with triethyl orthoformate or orthoacetate gave 9-R-furo[2, 3 4,5]pyrrolo[l,2-J][l,2,4]triazolo[3,4-/ [l,2,4]triazines (387) and 3- and 6-methyl as well as 3,6-dimethyl derivatives (Scheme 17). 

Recently, Nyffenegger et al. (07TL5069) have utilised the Sonogashira reaction for the functionalisation of 5[Pg.82]

Amino- 1-arabinofuranosy l-2( 1H )-pyrimidinone, C-221 4-Amino-7-(p-D-arabinofuranosyl)pyrrolo(2,3-d]pyrimidine, A-859 4-Amino-l-p-D-arabinofuranosyl-l, 3,5-triazin-2(l/0-one, F-1... 

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