Triazolo pyrimidine sulfonamide

Pyrazolo[4,3-d]pyrimidine and pyrazolo[3,4-d]pyrimidine sulfonamides have been synthesized as selective calcitonin inducers <02JMC2342>. A series of para-substituted 3-arylpyrazolo[3,4-d]pyrimidines have been synthesized and evaluated as inhibitors of lck kinase <02BMCL1687). The synthesis of 3-aryl-pyrazolo[4,3- f]pyrimidines as potential corticotropin-releasing factor (CRF-1) antagonists has been described <02BMCL2133>. Cyclization of 4-chloro-5-heteroimine-l,2,3-thiadiazoles furnished pyrazolo[3,4-d]pyrimidines, triazolo[4,5-d]pyrimidines and purines <02BMC449>. 

The target triazolo[l,5-c]pyrimidine sulfonamides 6 were prepared via coupling 7 with substituted benzenesulfonyl chlorides (Scheme 2). In these transformations, pyridine and a catalytic amount of dimethylsulfoxide (DMSO) were essential for the formation of 6. The reactive intermediate is believed to be the in situ generated sulhlimine 10 which allows for the relatively non-nucleophiKc amines to react with sulfonyl chlorides under mild conditions [7-8],... 

Triazolopyrimidine, Triazolo[l, 5-a]pyrimidine, Triazolo[l, 5-c]pyrimidine. Sulfonamide, Penoxsulam... 

The N-triazolo[l,5-c]pyrimidine sulfonamides and related compounds differ from their sulfonanilide counterparts by the orientation of the linkage between the triazoloazine and the aryl or heteroaryl ring. However, in most cases synthesis of sulfonamides is similar to the sulfonanilides, as the target molecules are formed by reaction of a sulfonyl chloride and an amine in the final step. Notably, the synthesis of arylsulfonyl chlorides account for much of the diversity in these molecules [32-36]. 

The structure-activity trends for triazolo[l,5-c]pyrimidine sulfonamides (13) have been studied extensively [32-36]. Table 2.4.3 summarizes the herbicidal activity... 

Scheme 2.4.4 outlines a general route for the synthesis of N-triazolo[l,5-a]pyrimidine sulfonamides (20) [48, 49]. 2-Amino-4,6-dimethoxypyrimidine (21) is reacted with thiocarbonyldiimidazole followed by hydroxylamine in the presence of a base to give 23, which is then reacted with various substituted benzene and pyridine sulfonyl chlorides (17 Scheme 2.4.3) in the presence of a catalytic amount of dimethyl sulfoxide and a base to give 20. 

The structure-activity trends for the triazolo[15-a]pyrazines have not been studied as extensively as other members of triazolopyrimidine sulfonanilides [51]. Table 2.4.10 shows the activity on broadleaf and grass species for a series of substitutions on the fused heterocyclic portion of 34. The highest levels of activity on grass and broadleaf species are observed when both 5- and 8-positions are substituted with methoxy (34, R = R = OMe). However, the herbicidal activity observed for 34 is weaker than that for the triazolo[l,5-a]pyrimidine sulfonamides. 

Wolt ID, ID Schwake, FR Batzer, SM Brown, LH McKendry, JR Miller, GA Roth, MA Stanga, D Portwood, DL Holbrook (1992) Anaerobic aquatic degradation of flumetsulam [N-(2,6-difluorophenyl)-5-methyl [l,2,4]triazolo[l,5a]pyrimidine-2-sulfonamide]. J Agric Food Chem 40 2302-2308. 

Compounds 272 are useful as herbicides and inhibitors of nitrification of amino nitrogen in soil, and they are used for the control of Echinochioa crusgalli without damage to rice. 5-Fluoromethyl-7-methoxy-l,2,4-triazolo-[l,5-a]pyrimidine-2-sulfonamides are useful for the control of pigweed (85USP4818273). 

Chlorination of thiobenzyl derivative 494 led to 557, whose reaction with aromatic amines afforded the ZV-aryl-1,2,4-triazolo[l, 5-c]pyrimidine-2-sulfonamide 558 (89EUP343752 93USP5177206). 

Synthetic studies focused on the bicyclic heterocycle led to the discovery of a new sub-class of sulfonamides where the triazolo[l,5-a]pyrimidine ring was replaced with a triazolo[l,5-c]pyrimidine ring. Further investigations led to the development of diclosulam (3) and cloransulam-methyl (4) for broadleaf weed control in soybeans, and florasulam (5) for broadleaf weed control in cereals. To fully explore this sub-class of sulfonamides, an investigation was initiated to determine if reversing the sulfonamide linkage (6) would lead to compounds with the spectrum of activity on weeds and crop selectivity different from 3, 4, and 5. 

Van Heertum JC, Gerwick IBC, Kleschick WA, Johnson TC (1992) Herbicidal alkoxy-1,2,4-triazolo[l,5-c]pyrimidine-2-sulfonamides. US 5163995... 

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