Palladium catalyzed indolization of 2-bromo or chloroanilines

A method for making substituted indole compounds comprising the steps of:

• reacting a 2-bromoaniline or 2-chloroaniline of formula (I)
• wherein:
• X is Br or Cl,
• R is H, alkyl, aryl, —C(O)C1-6alkyl, —C(O)-aryl, —S(O)2C1-6alkyl or —S(O)2aryl;
• R1 is C1-6 alkyl, C1-6 alkoxy, —CO2 C1-6 alkyl, C1-6alkylHNC(O)—,
• and
• with a substituted acetylene of formula (II)
• wherein
• R2 is acyclic or cyclic alkyl, aryl, or heterocycly;
• R3 is:
• phenyl optionally substituted with F, Cl, alkyl, aryl, CO2C1-6 alkyl or carboxamide, or R3 is heteroaryl selected from pyridine, pyrimidine, furan, thiophene, pyrrole and imidazole, optionally substituted with F, Cl, alkyl, aryl, CO2C1-6 alkyl or carboxamide, or R3 is trialkysilyl, alkyl, alkoxy;
• in the presence of a palladium catalyst, a ligand, and a base in a solvent to give a compound of formula (III);