Patent ID: 6608193
Filing Date: 2003-08-19
Classification: C07D

Abstract:
A method of preparing an amino-substituted-tetrahydroisoquinoline ring compound; wherein said compound comprises a structure selected from the group consisting of: represents a heterocycle, aryl, or hydrocarbocycle; represents a heterocycle; R1 is alkyl, aryl, heterocyclic moiety, amide, sulfonamide, urea, thiourea, or alcohol and R2 is alkyl, aryl, heterocyclic moiety, amide, sulfonamide, urea, thiourea, hydrogen, or alcohol; R3 and R4 are each independently an alkyl or aryl; n is from 0 to 1; R5 is the side chain of an amino acid and Z is NH, O or S; wherein the amino acid side chain may be selected from the group consisting of side chains of natural and synthetic amino acids; comprising the steps of (a) providing a support-bound amino-substituted-tetrahydroisoquinoline-carboxylic acid in the form of a carboxylate having the structure: wherein W represents a solid support and R1 is alkyl, aryl, heterocyclic moiety, amide, sulfonamide, urea, thiourea, or alcohol; (b) forming a support-bound intermediate by reacting the support-bound amino-substituted-tetrahydroisoquinoline-carboxylate with a reagent selected from the group consisting, of: (i) isocyanates having the structure R3NCO wherein R3 is an alkyl or aryl, (ii) thioisocyanates having the structure R4NCS wherein R4 is an alkyl or aryl, (iii) protected non-cyclic amino acids having the structure: wherein P is a protecting group, n is from 0 to 1, and R5 is the side chain of an amino acid, and (iv) protected cyclic amino acids having the structure: represents a heterocycle, P is a protecting group, and Y is NO2, NHP, OP, or SP, and (v) protected cyclic amino acids having the structure: represents a heterocycle, aryl, or hydrocarbocycle, P is a protecting group, and Y is NO2, NHP, OP, or SP; and (c) cyclizatively cleaving the support-bound intermediate to form the amino-substituted-tetrahydroisoquinoline ring compound.