Furo pyrazoles

H-Furo[3,4-e]pyrazole, 1,4-dihydro-4-oxo-l-substituted synthesis, 6, 989 Furo[2,3-d]pyrazoles synthesis, 6, 998 Furo[3,4-d]pyrazoles synthesis, 6, 998 Furo[2,3-d]pyridazine H NMR, 4, 984 synthesis, 4, 984... 

Merck has recently utilised a furo[2,3-b]pyridine core (554) as a bioisosteric replacement for the pyrazole scaffold of rimonabant (382) [328]. The same basic pharmacophore, that of two halo-substituted aryl groups and a third hydrophobic motif proximal to a hydrogen-bond acceptor, can be witnessed in the benzodioxole-based compounds, such as (555), disclosed by Roche [329]. 

The cycloaddition of nitrilimines toward furo[3,4-c]thieno[2,3-r7]-pyrazoles has been investigated as a function of the electron-withdrawing or electron-donating character of the substituents attached to the aromatic rings <2000H(53)917>. For instance, nitrilimine 459, obtained in situ from hydrazonoyl chloride 458, by base treatment with silver carbonate in dioxane, when reacted with 460, gives a mixture of compounds 461 and 63 (Scheme 53) <2000H(53)917>. 

Similar synthetic approaches have been used to synthesize furo [3,4-c]pyrazoles, e.g., conversion of 328 to 329 (74AKZ954). Reductive cyclization of 330 gives 331. Compound 330 is prepared by... 

Simultaneous formation of a two-ring system from acyclic intermediates has also been reported. For example, the reaction of carbonyl-stabilized sulfur ylides with nitrile imines afforded furo[3,2-c]pyrazoles (69TL853). 

Pfizer (Pharmacia) disclosed the development of potent Aurora-A kinase inhibitors containing the 3-aminothieno[3,2-c]pyrazole (80) and 3-amino-furo[3,2-c]pyrazole (81) scaffolds [195,196]. Extensive data was not reported... 

Reaction of the quaternized salts of 4-ethoxycarbonyl-3,5-dimethyl-f-phenylpyttolo(furo or thieno)[2,3-c]pyrazole 34 with the iodomethane quaternary salts of pyridine, quinoline, and isoquinoline in ethanol with catalytic piperidine gave 3-[4(f)]-monomethine cyanine dyes (e.g., 35). Additionally, 3-[2(4)]-trimethine cyanine dyes and 4-[2(4)]-di-3[2(4)]-tri-mixed methine cyanine dyes (e.g., 36 and 37, respectively) were similarly prepared from the intermediates derived by reaction of 34 with triethyl orthoformate in the presence of piperidine (Scheme 8) <2002CCS106f>. 

While cycloaddition approaches have been discussed extensively in this chapter, there are certain substitution patterns that are not amendable to such approaches. In these cases, the more traditional annelative approaches are necessary. For example, the 5,6-dihydropyrrolo[3,4-rf]imidazol-4(3//)-one (286) is obtained from the diamine (285) and triethyl orthoformate. If formamide is used in excess, 6-(formamidomethylene)-5,6-dihydropyrrolo[3,4-d]imidazol-4(3//)-one (287) is obtained (Scheme 53) <70JPS1732>. A variant of the Thorpe cyclization was employed in the preparation of 3-amino-4//-pyrrolo[3,4-c]isoxazoles (289) from a-cyanooximes (288) (Equation (66)) <68JMC453>. 3-Acyltetramic acid (290 X = NR2) and 3-acyltetronic acid (292 X = O) hydrazones undergo ready cyclization in refluxing xylene with catalytic p-toluenesulfonic acid to afford 4-oxo-l,4-dihydro-6/f-pyrrolo[3,4-c]pyrazoles (291) and 4-oxo-l,4-dihydro-6//-furo[3,4-c]pyrazoles (293), respectively (Equation (67)) <82SC43l>. The novel synthesis of 5-amino-6a-hydroxydihydro-6//-pyrrolo[2,3-j]isoxazole (296) from 3,4-disubstituted 4-(amino)isoxazol-(4//)-ones (294) is hypothesized to occur by the cyclization of the ketene aminal intermediates (295) (Scheme 54) <91S127>. 

Condensation of acetyl-tetronic or -tetramic acids with methyl- or phenyl-hydrazine leads to 3-(l-hydrazinoethyl)-tetronic and -tetramic add, respectively, which upon dehydration form 1-substituted 4-oxo-l,4-dihydro-6//-furo[3,4-c]pyrazoles (X=0) and -pyrrolo[3,4-c]pyrazoles (X=NH) (equation 20) (82SC431). 

C,/V- Diarylnitrile imines react with carbonyl-stabilized sulfonium ylides to give furo[2,3-d]pyrazoles (Scheme 4) (70TL605). 

H- 2-(4-Chlor-phenyl)-6-oxo-4,6-dihydro- E14b,... 

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