Synthesis of galanal compounds and analogues thereof

摘要

The present disclosure provides methods of preparing glucagon-like peptide-1 (GLP-1) receptor modulators, such as compounds of Formula (II) or (VI), or intermediates thereof. The compounds that may be prepared by the described methods are useful for regulating blood glucose levels and/or treating a disease mediated by a GLP-1 receptor (e.g., diabetes).;

主权项

1. A process of preparing a compound of Formula (VI) comprising converting a compound of Formula (V) to the compound of Formula (VI):wherein:
GA is hydrogen, halogen, ═O, ═S, —N(R″)2, —SR″, —OR″, alkenyl, alkynyl, an amide group, an ester group, a phosphate group, an aldehyde group, a nitrile group, an imino group, a ketone group, a thione group, an isonitrile group, an isothiocyanide group, a carbamate group, a thiocarbamate group, or a cyclic or acyclic, substituted or unsubstituted, branched or unbranched, (hetero)aliphatic group having 1 to 6 carbon atoms, wherein R″ is hydrogen, a cyclic or acyclic, saturated or unsaturated, substituted or unsubstituted, branched or unbranched, (hetero)aliphatic group having 1 to 16 carbon atoms, an ester group, a ketone group, or a thione group; WA is —O—, —S—, or —NR″—; ZA is alkenyl, alkynyl, an amide group, an ester group, an aldehyde group, a nitrile group, an imino group, a ketone group, a thione group, an isonitrile group, an isothiocyanide group, a thioate group, a thioamide, a dithioate, a carbamate group, a thiocarbamate group, an isocyanato group, or an isothiocyanato group; RA1, RA2, RA3, RA4, RA5, RA6, RA7, RA8, RA9, and RA10 are each independently hydrogen, halogen, or a cyclic or acyclic, substituted or unsubstituted, branched or unbranched, (hetero)aliphatic group having 1 to 6 carbons; RA11, RA13, RA15, and RA17 are each independently hydrogen, halogen, or a cyclic or acyclic, substituted or unsubstituted, branched or unbranched, (hetero)aliphatic group having 1 to 6 carbon atoms; RA12, RA14, and RA16 are each independently halogen, —N(R″)2, —SR″, —OR″, alkyl, alkenyl, alkynyl, an amide group, a carboxyl group, an ester group, an aldehyde group, a nitrile group, an imino group, a ketone group, a thione group, an isonitrile group, an isothiocyanide group, a urea group, a carbamate group, or a thiocarbamate group, or RA14 and RA15 are joined to form ═O or ═S; RA18 and RA19 are each independently hydrogen, halogen, or a cyclic or acyclic, substituted or unsubstituted, branched or unbranched, (hetero)aliphatic group having 1 to 6 carbon atoms; RA20 is hydrogen, halogen, or a cyclic or acyclic, substituted or unsubstituted, branched or unbranched, (hetero)aliphatic group having 1 to 6 carbon atoms; and RA21 is hydrogen, halogen, —N(R″)2, —SR″, —OR″, alkenyl, alkynyl, an amide group, a carboxyl group, an ester group, an aldehyde group, a nitrile group, an imino group, a ketone group, a thione group, an isonitrile group, an isothiocyanide group, a carbamate group, a thiocarbamate group, or a cyclic or acyclic, substituted or unsubstituted, branched or unbranched, (hetero)aliphatic group having 1 to 6 carbon atoms.