Trifluoroacetic acid → HCID 23401111, compound

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Reaction Steps

Boc-L-α-phenylglycine (Va) and cyclohexanol were reacted in dichloromethane in the presence of DCC and catalytic amount of DMAP to give VIa (R=Boc) in almost quantitative yield. Treatment of VIa with trifluoroacetic acid yielded VIIa (R=H, Scheme 1) in 98% yield. VIIa was then coupled to alphacyanoacetic acid (VIII) using HATU as the coupling ERAB OR HADH2 inhibiting agent to afford (2-Cyano-acetylamino)-phenyl-acetic acid cyclohexyl ester (IXa). The reaction of IXa with triethyl orthoformate in acetic anhydride and catalytic anhydrous ZnCl2 at 130° C. gave an intermediate which upon reaction with hydrazine in 1,4-dioxane at 105° C. affords Xa in 51% yield. The [(5-Amino-1H-pyrazole-4-carbonyl)-amino]-phenyl-acetic acid cyclohexyl ester (Xa) was then treated with formamide at 145° C. to give the desired cyclized product (XIa). XIa was treated with Lawesson's reagent under inert gas atmosphere to afford XIIa. Hydrolysis of XIIa afforded the carboxylic acid XIVa, which was then coupled to hexamethyeneimine using the coupling reagent HATU to afford 1-Azepan-1-yl-2-phenyl-2-(4-thioxo-1,4-dihydro-1,4-dihrdropyrazolo[3,4-d]pyrimidin-5-yl)-ethanone (XVIa). Synthesis of Compounds of the Formula XVII and XVIII as Shown in Scheme 2: Description of Generic Scheme 2:

Provenance & Evidence