A Short Synthesis of the 2-Bromo-N,9-dimethyl-6,7,8,9-tetrahydro-5 H-pyrido[2,3-b]indol-6-amine Building Block

Article abstract of DOI:10.1021/acs.oprd.9b00222

A concise synthesis of pharmaceutically useful (R)-tert-butyl N-(2-bromo-9-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-b]indol-6-yl)-N-methylcarbamate building block 11 is described. The racemic intermediate 17 was prepared in a single step from 2-bromo-6-(1-methylhydrazinyl)pyridine sulfate salt (14) and N,3,3-trimethyl-1,5-dioxaspiro[5.5]undecan-9-amine hydrochloride salt (16). Chiral separation of racemic intermediate 17 by diasteromeric salt recrystallization afforded the diasteromeric salt 18 in 37% yield, which was Boc-protected to afford building block 11. Thus, the process for the synthesis and chiral separation by diasteromeric salt crystallization allowed the synthesis of chiral building block 11 in kilogram quantities in 18% overall yield.