Convergent processes for the synthesis of a GARFT inhibitor containing a methyl substituted thiophene core and intermediates therefor

摘要

The invention relates to processes for the preparation of a GARFT inhibitor containing a methyl substituted thiophene core having the following structure: chemistry chemdraw filechemistry mol file;wherein each of R¹ and R² are independently a hydrogen atom or a moiety that together with the attached CO₂ forms a readily hydrolyzable ester group; from an intermediate of the formula chemistry chemdraw filechemistry mol file;wherein R³ is a moiety that together with the attached CO₂ forms a readily hydrolyzable ester group; ;Pg¹ is an amino protecting group; ;R⁴ is H; ;or Pg¹ can optionally be taken together with R⁴ and the nitrogen to which Pg¹ and R⁴ are attached to form (i) an imine; or (ii) a fused or bridged bicyclic ring or a spirocyclic ring, wherein said ring is saturated and contains from 5 to 12 carbon atoms in which up to 2 carbon atoms are optionally replaced with a hetero moiety selected from O, S(O)_j wherein j is an integer from 0 to 2, and NR⁸, provided that two O atoms, two S(O)_j moieties, or an O atom and a S(O)_j moiety are not attached directly to each other; ;R⁵ is selected from the group consisting of CC and CHCH; and ;R⁸ is independently H or C₁-C₆ alkyl; ;to form the compound of the formula (I) that is optically pure; and to processes for preparing intermediates thereof.