Pyrazolo pyrimidines with electrophiles

B. Chemical Properties of Pyrazolo[3,4- /]pyrimidines 1. Reactions with Electrophiles... 

Reaction of 2-amino-3-phenylazo-5-methyl-6,7-dihydropyrazolo [ 1,5-a] -pyrimidine-7-one (209) with ACOH/H2SO4 gives the pyrazolo[l,5-a]-pyrimidine derivative 210 (77JHC155). This reaction can be looked at as electrophilic substitution of the arylazo function by the proton. Similarly, 4,5,6,7-tetrahydro-2-phenyl-3-phenylazo-5-oxopyrazolo[l,5-a] pyrimidine gives 4,5,6,7-tetrahydro-2-phenyl-5-oxopyrazolo[l,5-a]pyrimidine 212 by the action of acetic/hydrochloric acid (75T63). 

Pyrazolo[l,5-fl]pyrimidine derivative 222, when treated with water, partially changes into 223. This reaction is assumed to proceed via attack of base at C-7 (81CPB1548 81JHC163). The C-6=C-7 double bond in 222 adds a variety of electrophiles (81CPB1548 81JHC163 83H(22)1913). Thus, treatment of 222 with acetic acid and water at 70°C affords 8-carbeth-oxy-3-substituted-7-methyl-6W-pyrazolo[ 1,5-a]-1,3-diazepin-6-one (224). Compound 222 reacts with phenylhydrazine to yield the pyrazolo[3,4-6,7]pyrazolo[l,5-n]pyrimidine derivative 225. The double bond in 222 also adds diazoalkanes to yield the pyrazolo[l,5-a]pyrimidine derivatives 226 (81CPB1548 81JHC163 83H(22)1913). 

Vega developed an efficient synthesis of pyrazolo[3,4- /]pyrimidines based on the electrophilic properties of nitrilium salts formed by reaction of 5-aroylaminopyrazoles, nitriles and Lewis acids. Treating iminolyl halides with nitriles with SnCU gave rise of the nonisolated nitrilium salts, which underwent cyclization to generate the desired pyrazolo[3,4-i/]pyrimidines in moderate to good yields. A similar approach was extended to the preparation of 4-amino-2-phenylquinazolines via cyclization of V-arylbenzamides with cyanamide catalyzed by TiCU. ... 

Another ingenious example of catalyst-mediated regiocontrol was published by Bedford in the direct arylation of pyrazolo[l,5-d]pyrimidine 83 (Scheme 39) (2015AGE8787). This core displays two reactive sites as determined via DFT calculations C7-position turned out to be the most acidic while the C3-position is the most susceptible for electrophilic substitution. Selective C7-arylation (83 85) was achieved with a Pd(OAc)2/SPhos... 

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