Pyrazolo 4,5-dihydro

Treatment of pyrazolo[l,5-a]quinoline-3,3,4-tricarboxylates 79 with CS2CO3 afforded 2,3-dihydro-l//,7//-pyrido[3,2,l-i/]cinnoline-3,3,8-tricar-boxylates 80 (96BCJ1371). 

Note Quinoxalinecarbohydrazides, their derivatives, and quinoxalinecarbonyl azides are especially useful for cyclizations typical examples are given here. 4-Oxo-Af -phenyl-3,4-dihydro-2-quinoxalinecarbohydrazide (127) gave 1-phe-nyl-l//-pyrazolo[3,4-h]quinoxaline-3(2//)-one (128) (TsOH, AcOH, 95°C,... 

CN l-[[3-(4,7-dihydro-l-methyl-7-oxo-3-propyl-l//-pyrazolo [4,3- pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4-methylpiperazine... 

See Ethyl 6-ethoxycarbonyl-3,4-dihydro-l,l,3-trioxo-2-pyrazolo [3,4-d]isothiazole-2-acetate... 

Treatment of pyrazolo[l,5- ]quinoline-3,3,4-tricarboxylates 75 with Cs2C03 afforded 2,3-dihydro-177,777-pyr-ido[3,2,l-(/]cinnoline-3,3,8-tricarboxylates 76 (Equation 15) <1996BCJ1371>. 

Arnino-6,7-dihydro-l //,5//-pyrazolo[ 1,2- pyrazol-l-onc 269 is easily obtained in 57% yield as its hydrochloride by acid-catalyzed ring closure of nitrile 268 using hydrochloric acid. A better yield is described for the synthesis starting from the N-protected compound 267. Treatment with hydrochloric acid provides crystalline hydrochloride of 268, which is then cyclized by heating in ethanol (Scheme 33) <2001JHC613>. 

Isocyanides and dialkyl acetylenedicarboxylates in the presence of 2,4-dihydro-3//-pyrazol-3-ones 344 in acetone at ambient temperature undergo a smooth 1 1 1 addition reaction to produce highly functionalized 7-oxo-17/,7H-pyrazolo[l,2-tf]pyrazole derivatives 345 in 69-81% yields (Equation 47) <2005T3963>. 

A novel class of tricyclic lymphocyte specific kinase (Lck) inhibitors containing the 9,10-dihydro-8//-pyrazolo[l,2-tf]pyrimido[4,5-c]pyridazin-8-one moiety has been reported <2006BML4257, 2006H(68)2037>. The most promising compound, 708, advanced to pharmacokinetic evaluation <2006BML4257>. 

Aminorhodanines 284 reacted with ethyl 2-bromo-3,3-diethoxypropionate to provide 2,3-dihydro-pyrazolo[5,1 -b -thiazoles 285. The mechanism proposed for the cyclization involved via a sequential condensation-sulfur extrusion reaction (Equation 125) <1994JHC1719>. 

The reaction of 2-anilino-l,4-naphthoquinone 374 with benzoylacetic acid hydrazide gives 3-hydrazino-pyrazolyl derivative 375, that is acetylated to produce 5-[[l,4-dihydro-l,4-dioxo-3-(phenylamino)-2-naphthalenyl]sulfonyl]-3-methyl-6-phenyl-5/7-pyrazolo[5,l-c][l,2,4]triazole 51. This latter derivative is also obtained in 51% yield from reaction of 374 with benzoylacetic acid hydrazide in the presence of a mixture of acetic acid-sodium acetate <2004PS(179)1907> (Scheme 39). 

Alkenylidene cyclopropanes react readily with 246 to yield 1,4-diazo-bicyclo[3,3,0]oxtanes, whereas methylidene cyclopropane reacts only very slowly with 246 to yield a 2 + 2 cycloadduct (73AJ1553). Compound 246 also reacts with 5-methylfuran-2(3//)-one in an acyl-ene reaction to yield 7-acetyl-6,7-dihydro-2-phenyl-2.ff-pyrazolo[I,2-a]-l,2,4,-triazol-l,3, 5-trione [80JCS(P1)843]. 

The 1,3-dipolar cycloaddition of diarylnitrile imines 98, generated in situ from arylhydrazones with chloramine T or from a-chlorobenzylidenephenylhydrazine with triethylamine, to some 5-substituted 2-methylpyridazin-3(2//)-ones 88, 99-101 has been shown to afford l,3-diaryl-l,5-dihydro-4//-pyrazolo[3,4- ]pyridazin-4-ones 102 regioselectively (Scheme 21) <2000JMT(528)13>. 

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