3- Aminopyrazole-4-carboxylic acid

C4H5N302 3-aminopyrazole-4-carboxylic acid 41680-34-6 25.00 1.3738 2 2967 C4H602 trans-2-butenoic acid 107-93-7 71.40 1.1018 1... 

Ready formation of pyrazolo[3,4-4 pyrimidines from reaction of 5-aminopyrazole -carboxylic acid derivatives is a well-established route to derivatives of this ring system. A recent application is the conversion of 286 into 288 by reaction with formamide and NIS 287 (Equation 40) <2002BML1687>. 

Aminopyrazole has been prepared by a Curtius degradation of pyrazole-3(5)-carboxylic acid hydrazide,2 3 by saponification and decarboxylation of ethyl 3-aminopyrazole-4-carboxy-late 4 obtained from ethyl ethoxymethylenecyanoacetate and hydrazine, and by the present procedure.6,6... 

A new route to l-aryM-aminopyrazole-5-carboxylic acid derivatives via reacting arylhydrazononitriles with halocar-boxylic acid derivatives has recently been reported. The pyrazoles so obtained were used for synthesis of arylazolo[4,3-. 

Chebanov et al. [202] noted that condensation of the unsaturated acids 236 with 5-aminopyrazoles 220-222 never yielded isomers with opposite location of the aryl and carboxyl groups on the pyridine or pyrimidine rings, respectively. In the case of the multicomponent reaction of aminopyrazoles 220-222 with pyruvic acid 239 and aromatic aldehydes a different direction was observed. Refluxing of the starting materials in acetic acid led exclusively to pyrazolo[3,4-Z ]pyridine-4-carboxylic acids 249-251 instead of the anticipated carboxylic acids 243-248 (Scheme 3.69). The three-component procedures led only to the formation of heteroaromatized compounds even under a nitrogen atmosphere [202]. 

Fig. 2.4.9. Dimeric 3-aminopyrazole-5-carboxylic acid in its 1 1- and 2 1-complex with a tetrapeptide.

Fig. 2.4.10. Synthesis of oligomeric aminopyrazoles starting from 3-nitropyrazole-5-carboxylic acid 15 (i) HCI, MeOH ...

Allopurinol, 1,5-dihydro-4//-pyrazolo[3,4-d]pyrimidin-4-one (53), was first synthesized by Robins <56JA784> and by Schmidt <58HCA1052) from 5-aminopyrazole-4-carboxylic acid derivatives. Several syntheses starting from a simple acyclic intermediate have been reported. Thus, reacting ethyl alkoxymethylene cyanoacetate with hydrazine and formamide at 14(M80°C gave allopurinol in high yield. An acid catalyst lowers the temperature required for cyclization of the intermediate 4-alkoxycarbonyl-3-aminopyrazole and raises the purity and the yield of allopurinol <69BRPI 284084). 

For purposes of classification the 4-aminopyrazoles are considered to be 4-imino-2-pyrazolines and analogs of 2-pyrazolin-4-ones. These compounds are listed in Table XL. Such compounds can be prepared by direct cyclization using ethyl diazoacetate and ethyl cyanoacetate.92 This is the same as eq. 243, except that the malonic ester is replaced by ethyl cyanoacetate. Purines can be hydrolyzed to 4-imino-2-pyrazolines by using strong acid.1210 1846 By far the most frequently used preparation is reduction of appropriately substituted pyrazoles, such as 4-nitro,368,812,819,1015,1019,1049 4-nitroso1165 or 4-aryl-azo.671 974,995 The hydrolysis of the carbethoxy 4-imino-2-pyrazolines derived from ethyl cyanoacetate and ethyl diazoacetate forms 4-imino-2-pyrazolin-3-carboxylic acid which is readily decarboxylated to the parent compound.92... 

A-Acylation is one of the most important synthetic methods in the chemistry of A -aminoazoles, and is widely used in various heterocyclizations as well to protect the amino group. There are numerous papers devoted to acylation of practically all types of N-aminoazoles, with the exception of A-aminopyrazole. As acylating agents, carboxylic acids... 

Most of these reactions were carried out with 4-amino-l,2-dihydro-l,5-dimethyl-2-phenyl-3/f-pyrazol-3-one (4-aminoantipyrine). The acid chlorides were prepared separately or generated in situ from the corresponding carboxylic acid in the presence of the aminopyrazol-3-ones. 

The acylation of 4-aminoantipyrine 30 took place with acid chlorides 45d,f and the respective acid chlorides prepared in situ from the carboxylic acids 45a c,e. Thus, 2-cyanoarylacrylic acids 45a c.e, triethylamine and 4-aminopyrazol-3-one 30 at 0 °C were treated with phosphorus oxychloride while acid chlorides 45d,f were treated with triethylamine and pyrazol-3-one 30 at 0 °C to afford the corresponding A -(3-oxopyrazol-4-yl)acrylamides 46a-f in moderate yields (91JIC612) (Scheme 11). 

JV-dichloromethylenesulfonamide (186a), 5-aminopyrazole-4-carboxylic acid (38, Et = H) is converted to a pyrazolo[3,4-d][l,3]oxazine (186b).113a... 

Tris(ethoxycarbonyl)-l,3,5-triazine serves as an azadiene in reaction with 5-aminopyrazoles to produce purine isosteres, pyrazolo[3,4-t ]pyriniidines." In order to overcome the relative instability of 5-aminoiniidazoles, required for analogous synthesis of purines, 5-aminoiniidazole-4-carboxylic acids can be used, in situ decarboxylation producing the required dienophile."" ... 

An elegant method for the utility of unstable 3-unsubsti-tuted 2-aminothiophene derivatives 385 in the Yonemitsu-type reaction has been elaborated by Krayushkin et al. (Scheme 13.81) [153]. Starting from stable 4,5-disubstituted ethyl 2-aminothiophene-3-carboxylates 383, the ester functionality is hydrolyzed to yield the corresponding alkali metal carboxylates 384. These are directly subjected to the three-component Yonemitsu-type reaction in acetic acid as the reaction medium. Protonation of the carboxylate followed by decarboxylation generates the 2-aminothiophene derivatives 385 that directly undergo Yonemitsu reaction without the need of isolation of those intermediates. This method has been applied to methyl 2,4-diaminothiazole-5-carboxylates 388 [154], ethyl 5-aminopyrazole -carboxylates 389 [155], dimethyl 3-aminopyrrol-2,4-dicarboxylates 390 [156], 4,5-disubstituted methyl 3-aminothiophene-2-carboxylates 391 [157], dimethyl 3-amino-4-phenylthiophene-2,5-dicarboxylate 392 [156], and ethyl 5-amin(Mmidazol-4-carboxylates 393 [158]. 

Murlykina et al. [55] studied the three-component reaction of 5-aminopyrazoles (24), salicylic aldehydes (25) with pyruvic acid (26). The reaction involving pyruvic acid can be selectively directed to the formation of either 3-aryl-10,ll-dihydro-4,10-methanopyrazolo[4,3-c][l,5]benzoxazocine-4-carboxylic acids (27) or 3,6-diarylpyrazolo[3,4-fc] pyridine-4-carboxylic acids (28), while the reaction involving arylpyruvic acids leads only to 7-hydroxy-2,5,6-triaryl-... 

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