Sodium Carbonate → 6,7-dimethoxy-1-[4-(3-methoxypyridin-4-yl)benzyl]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

Participants

Reaction Steps

The synthesis of 6,7-dimethoxy-1-[4-(3-methoxypyridin-4-yl)benzyl]-1,2,3,4-tetrahydroisoquinoline hydrochloride salt 12 is shown in Scheme 3. Reaction of 1-(4-bromobenzyl)-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 1 with 3-methoxypyridine-4-boronic acid 10 in the presence of Palladium(II) acetate, triphenylphosphine, and Na2CO3 yielded 6,7-dimethoxy-1-[4-(3-methoxypyridin-4-yl)benzyl]-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 11 which was then treated with 2 M HCl solution in diethylether to get compound 12. N-[4′-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-ylmethyl)biphenyl-2-yl]-methanesulfonamide hydrochloride salt 15 was prepared by the reaction of 1-(2′-Methanesulfonyl-aminobiphenyl-4-ylmethyl)-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 14 with 2 M HCl solution in diethylether. Compound 14 was obtained by the Suzuki coupling of compound 1 with (2-methylsulfonylaminophenyl)-boronic acid 13 using Palladium(II) acetate, triphenylphosphine, and Na2CO3 in isopropanol (scheme-4).

Provenance & Evidence