Synthesis of 1-aroylmethyl-and 1-aryloxymethyl-3,4-dihydroisoquinolines and their effects on blood clotting

Abstract

Acylation of a number of tertiary enamines with aroylchlorides was used to synthesize 1-aroylmethyl-3,4-dihydroisoquinolines. Reaction of 1-chloromethyl-3,3-dimethyl-3,4-dihydroisoquinoline with phenols with interphase catalysis was also used to make 1-aryloxymethyl-3,4-dihydroisoquinoline derivatives. 1-Aroylmethylisoquinolines characteristically had a hemostatic effect, while 1-aryloxymethyl-3,4-dihydroisoquinolines had an anticoagulant effect. The most active compound increased blood clotting by 17.7%.

Succinct Syntheses of Methopholine, (±)‐Homolaudanosine, and (±)‐Dysoxyline via Metal‐free One‐Pot Double Alkylation on 1‐Methyl‐3,4‐dihydroisoquinolines

“…Through solvent screening processes, DCE and CH 3 CN turned out to be better than other solvents for the formation of double alkylating product 3a (entries 2–6). As alkylation at the C1‐methyl of iminium salt was known to be enabled by converting iminium salt to enamine with the help of bases, addition of bases, such as Na 2 CO 3 , DIPEA, Et 3 N, DBU, and NMP, was performed in DCE and CH 3 CN (entries 7–16). Apparently addition of the base was beneficial to increase the yield of 3a .…”