CONVERGENT SYNTHESIS OF A GARFT INHIBITOR CONTAINING A METHYL SUBSTITUTE THIOPHENE CORE AND A TETRAHYDROPYRIDO`2,3-D! PYRIMIDINE RING SYSTEM 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 (I), wherein each of R<1> and R<2> 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 (III), wherein R<3> is a moiety that together with the attached CO2 forms a readily hydrolyzable ester group; Pg<1> is an amino protecting group; 10 R<4> is H; or Pg<1> can optionally be taken together with R<4> and the nitrogen to which Pg<1> and R 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)S wherein j is an integer from 0 to 2, and -NR<8>-, provided that two O atoms, two S(O); moieties, or an O atom and a S(O); moiety are not attached directly to each other; R<5> is selected from the group consisting of -C=-C- and -CH=CH-; and R<8> is independently H or C1-C6 alkyl; to form the compound of the formula (I) that is optically pure; and to processes for preparing 20 intermediates thereof.