CIS, ENDO-2-AZABICYKLO/3.3.0/OKTAN-3 -KARBOXYLSYROR OCH DERAS ESTRAR, SAMT FOERFARANDE FOER DERAS FRAMSTAELLNING.

摘要

The invention relates to cis,endo-2-azabiscyclo- [3,3,0]octane-3-carboxylic acids and their esters with the formula IIIa or IIIb, where W is hydrogen, a C1-C6 alkyl group or a C7-C8 arylalkyl group. The invention also relates to the salts of these compounds. To prepare the compounds in question by the process according to the invention, an enamine with the formula VI (where X1 is a C2-C10 dialkylamino group or a group with the formula VII, where m and o are 1-3, (m + o) is at least 3 and A is CH2, NH, O or S) is reacted with N-acylatedβ-halo-α-aminocarboxylic acid esters with formula VIII (where X2 is a nucleophilic group, Y is a customary protective group and R2 is a C1-C5 alkyl or a C7-C9 arylalkyl group), or it is reacted with acrylic acid esters with formula IX (where Y1 and Y2 are the same as in formula X above and R2 and Y1 are the same as above). The resulting compounds are then cyclized with strong acids, accompanied by an acylamide and ester cleavage, to give compounds with formula XIa or XIb. These compounds are converted, by catalytic hydrogenation or reduction with a borane-amine complex or complex boron hydrides, into compounds with formula IIIa or IIIb, where W is hydrogen. These compounds are possibly esterified to prepare compounds with formula IIIa or IIIb, which contain a C1-C6 alkyl group or a C7-C8 arylalkyl group. The compounds according to the invention can be used as intermediates in the preparation of therapeutically active cis,endo-2-azabiscyclo[3,3,0]octane-3-carboxylic acid derivatives. IIIa, IIIb, VI, VII, VIII, IX, X, XIa, XIb