Consecutive Pschorr-Sandmeyer reactions in a pyrazole series. Part 2. Access to the [2]benzopyrano[4,3-c]pyrazole system of pharmaceutical interest

摘要

The diazonium salts obtained from 2-amino-N-methyl-N-(1-phenyl-3-methylpyrazol-5-yl)benzamide were reacted with cuprous oxide or copper at 5 or 25 degrees C under different pH conditions. Cuprous oxide at 25 degrees C and pH 6.25 yielded the racemic epimers (3'SR,4'RS)-and (3'SR,4'SR)-4'-hydroxy-2',4'-dihydro-2,5 dimethyl-2'-phenylspiro[isoindoline-1,3'-3'H-pyrazol]-3-ones 2 and 10 respectively, (RS)-2',4'-dihydro-2,5'-dimethyl-2'-phenylspiro[isoindoline 9 and N-methylphthalimide 8, The thermal transformation of 2 and 10 into the potentially pharmacologically active 3-methyl-1-phenyl[2]benzopyrano[4,3-c]pyrazol-5(1H) 4 was strongly dependent on the structure of the two epimers, When I was reacted with cuprous oxide or copper sulfate and sodium halide (chloride or bromide), in the presence of ascorbic acid as initiator, a mixture of epimers (3'SR,4'RS)- and (3'SR,4'SR)-4'-chloro(or bromo)-2',4'-dihydro-2,5'-dimethyl-2'-phenylspiro[isoindoline-1,3'-3' H-pyrazol]-3-ones 6b and 7b (or 6c and 7c) was obtained. The same epimers were obtained when the diazonium halides (chloride and bromide) 1b,c obtained from 2-amino-N-methyl-N-(1-phenyl-3-methyl-1H-pyrazol-5-yl)benzamide were treated with the appropriate classical Sandmeyer catalysts. The formation of the spiro compounds is based on consecutive Pschorr and Sandmeyer reactions. The X-ray crystal structures of the epimers 2 and 10 have been determined, confirming the given formulations. [References: 21]