Two syntheses of 7,8‐dichloro‐1,2,3,4‐tetrahydroisoquinoline‐1‐¹⁴C

Abstract

Two complementary radiosynthetic routes to the potent PNMT inhibitor 7,8-dichloro-1 ,2,3,4-tetrahydroisoquinol i ne-l -l 4C(1) from 2,3-dichl orobenzal dehydeformyl-C(Q) are described. In the Pomeranz-Fritsch sequence isoquinoline 6 was prepared from Schiff's base 2.furnished 1 in 28% radiochemical yield from 4. sequence, 4 was converted via amino alcohol 7 to chloro amine 6. the latter with aluminum chloride/ammonium chloride (fusion, 190 "C) yielded labeled Jin 31% radiochemical yield from 2. 14 -Catalytic hydrogenation of fi (H2/Pt02) In the aluminum chloride fusion Treatment of m. i s 7.8-dichloro-l,2,3,4-tetrahydroisoquinol ine hydrochloride (1. S K f F 64139-A).(4) studies, we explored two complementary synthetic approaches both of which posi-One of the most potent of these agents. J I J In order to prepare carbon-14 tagged material for metabolite tioncd the carbon label in the 1-posltion of the tetrahydroisoquinoline. (5) The cmcn intermediate for the herein described methods was 2,3-dichlorobenzal-dehy~!e-formyl-'~C, readfly prepared from K CN. 14 RESULTSThe classical approach i s illustrated in SCHEHE 1. This method, which utilized the Pmeranz-Fritsch reaction(6a) for cyclization, produced 1 in 26-28 radiochemical yield from aldehyde 2. Commercial 2,3-dichloroiodobenzene SCHEME 1 CI CI DIBAL/

Diastereoselective electrophilic substitution of α-amino-substituted benzylic organometallics

“…Tetrahydroisoquinolines 8 and 9 were synthesized according to a modification of a procedure described in ref. 19. The starting amino alcohol (2.5 mmol) was dissolved in decalin (1 ml) in a 25 ml flask equipped with reflux condenser and magnetic stirrer under dry Ar.…”