5-Amino-3-methylpyrazoles

The preparative route to [l,5-f][l,3,5]thiadiazine-2-ones 312 is outlined in Scheme 65. Thus, 5-amino-3-methyl-pyrazole-l-carbothioamides 313, obtained from the reaction of 5-amino-3-methylpyrazole (314) with isothiocyanates, react smoothly with trichloromethyl chloroformate to afford 312 (Scheme 65) <2004JFA1898>. 

Dandia and coworkers [86] reported a three-component reaction of isatin, a-cyanoacetic ester, and 5-amino-3-methylpyrazole to produce pyrazolopyridinyl spirooxindoles 155 in 82-93% yields by using sodium chloride as the inductor in water (Scheme 12.62). 

In a catalyst-free, aqueous-mediated MCR facilitated by sonication, isat-ins 200, 5-amino-3-methylpyrazole 201 and a-mercaptoacetic acids 202 reacted to form spiro(indole-3,4 -pyrazolo[3,4-e][l,4]thiazepines) 203 in high yield. Replacement of the isatin with acenaphthylene-1,2-dione or N-substitued piperidin-4-ones gave the corresponding spiro(pyrazolo-1,4-thiazepines) (13RA18992). 

A novel MCR on water for the synthesis of spirooxin-doles was reported by Dandia in 2012 [76]. The reaction of easily available isatins 134, malononitrile 54/a-cyanoacetic ester 137, and 5-amino-3-methylpyrazole 135 catalyzed by... 

Pyrazolo[l,5-fl]pyrimidine 58 and its hydrated form were obtained by reaction of 5-amino-3-methylpyrazole with 2,6-bis(trifluoromethyl)-4-pyrone (57) [26]... 

Interestingly, when 5-amino-3-methylpyrazole reacted with Meldrum s acid and benzaldehydes in aqueous PEG 400, pyrazolo[3,4-fc]pyridines 129 were formed with good yields (Scheme 74) [105]. In the model reaction, it was demonstrated that the solvent can be recycled for up to five nms with limited decrease of yields. The reaction was foxmd to be regioselective and the structure of the products was xmambiguously confirmed by X-ray crystallography of 129 (R=4-OMe). This reaction was also successfully performed using n-butyraldehyde instead of benzaldehydes. 

Surprisingly, there are very few examples of successful fV-oxidation of pyrazoles. Simple fV-alkylpyrazoles generally do not react with peracids (B-76MI40402,77JCS(P1)672). The only two positive results are the peracetic acid (hydrogen peroxide in acetic acid) transformation of 1-methylpyrazoIe into 1-methylpyrazole 2-oxide (268) in moderate yield and the peroxy-trifluoroacetic acid (90% hydrogen peroxide in trifluoroacetic acid) transformation of 5-amino-l-methylpyrazoIe into l-methyl-5-nitropyrazoIe 2-oxide (269). 

In addition to (461), Dorn has described the imine (463) isolated from 5-amino-l-methylpyrazole and arenesulfonyl chloride (80CHE1). Upon heating, or in the presence of triethylamine, it undergoes rearrangement to the more stable 5-bis(arylsul-fonamido)pyrazoles (464). 5-Iminopyrazolines (461) react with acyl chlorides at the exocyclic nitrogen atom to afford amidopyrazolium salts (B-76MI40402). 

In aqueous solutions, the prevailing process is the primary attack of the unsubstituted nitrogen atom of alkylhydrazines at the terminal carbon atom of diacetylene with predominant formation of l-alkyl-5-methylpyrazoles (18) (73DIS). The content of isomeric l-alkyl-3-methylpyrazoles is less than 10% (GLC). In the authors opinion, this different direction of the attack at diacetylene in aqueous media is related to the hydration of alkylhydrazines and the formation of ammonium base RN" H2(0H) NH2, in which the primary amino group becomes the major nucleophilic center. 

Amino-4-acetyl-5-methylpyrazole acts as a monodentate ligand binding to zinc via the tertiary ring nitrogen donor. The mononuclear 2 1 complex was structurally characterized with two... 

Lipson VV, Shirobokova MG, Shishkin OV et al (2006) Synthesis of partially hydrogenated pyrazolo[3, 4-b]quinolinones by condensation of 3-amino-5-methylpyrazole with aromatic aldehydes and dimedone. Russ J Org Chem 42(7) 1015-1021... 

The same strategy had application in several other heterocyclic compounds, to obtain either amine or carboxylic acid derivatives. A process for the production of 4-amino-5-methylpyrazole derivative 325 using the Beckmann rearrangement as a key step was the subject of a new patent ° (equation 119). 

Tetraamminehydroxynitratoplatinum(IV) nitrate, 4594 Tetraamminepalladium(II) nitrate, 4588 Tetraamminezinc peroxodisulfate, 4586 l,4,8,ll-Tetraazacyclotetradecanenickel(II) perchlorate, 3376 Tetrakis(/u,3-2-amino-2-methylpropanolato)tetrakis(/Li2-2.amino-2-methylpropanolato)hexacopper(II) perchlorate, 3883 Tetrakis(3-methylpyrazole)cadmium sulfate, 3716 Tetrakis(3-methylpyrazole)manganese(II) sulfate, 3717 Tetrakis(4-iV-methylpyridinio)porphinecobalt(III)(5 +) perchlorate, 3908 Tetrakis(4-iV-methylpyridinio)porphineiron(III)(5+) perchlorate, 3909 Tetrakis(pyrazole)manganese(II) sulfate, 3538... 

Condensation of the intermediates 146-151 with either ethyl 5-amino-l-methylpyrazole-4-carboxylate or ethyl 2-aminothiophene-3-carboxylate using sodium hydride in refluxing dioxane gave the corresponding 4-hydroxy-l-methyl-pyrazolopyridine or 4-hydroxythienylpyridine esters, respectively (Equation 52 Table 28) <2003BMC2991>. 

A mass spectrometric study of 3-amino- and 5-amino-l-methyl-4-nitropyrazole and 3-nitro-, 5-nitro-4-amino-l-methylpyrazoles has been performed [1286], The highest relative intensity of the [M-NO]+ peak is observed with 5-amino-l-methyl-4-nitropyrazole. The authors believe this to be related with the pyrazole ring 7t-excessive position 4 and the easy transmission of the electronic effect of the amino group through the (C-4)-(C-5) bond. The [M-NO]+ peak relative intensity is minimal for 4-amino-l-methyl-3-nitropyrazole. This indicates a lower stabilization of the [M-NO]+ ion by the N-l atom compared with that produced by the N-2 atom seemingly due to the electron-withdrawing properties of the pyrazole ring N-2 atom [1286],... 

Polyfluorinated aliphatic aldehydes reacted with 1-phenyl-3-methylpyrazol-5-one, l-phenyl-3-methyl-5-amino (N,N-dimethylaminomethylenamino)pyrazole, and l-phenyl-3-aminopyrazol-5-one at room temperature in the absence of catalyst with formation of 4-(l-hydroxypolyfluoroalkyl)pyrazoles <2000JFC(101)111>. Dehydration of the 4-(l-hydroxypolyfluoroalkyOpyrazoles with morpholinosulfur trifluoride generated 4-polyfluoroalkylidenepyrazoles, which were active dienophiles and reacted with 2,3-dimethylbutadiene and cyclopentadiene forming spirocyclic pyrazole derivatives. 

Amino-5-trifluoromethyl-177-pyrazoles were synthesized by cyclocondensation reactions of 4-amino-4-ethoxy-1,1,1-trifluorobut-3-en-2-ones with hydrazines <2006S1485>. / -Alkoxyvinyl trifluoromethyl ketones 555 reacted with methylhydrazine to yield 3-(trifluoromethyl)-l-methylpyrazoles 556 (Equation 113) <2003JHC1087>. 

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