Synthesis of clomipramine‐d₈

Abstract

SUllMARYThe synthesis of deuterium labelled clomipramine which is an antidepressant drug is described. Eight deuterium atoms have been incorporated specifically into the nonaromatic part of the molecule --six atoms at 1, 2, and 3 positions of the dimethylaminopropyl side chain and two atoms at the 10 and 11 positions of the molecule. 1,1,2,2,3,3-Hexadeutero-3-dimethylaminopropyl chloride has been synthesized for this purpose and used for the construction of the labelled side chain.

Synthesis of stable‐isotope‐labeled N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide and N‐(3‐dimethylaminopropyl)‐N′‐ethylurea

“…The first steps of the synthesis were based on the known synthesis of [D 6 ] 3-dimethylaminopropyl alcohol. 5 (3). The nitrile of compound 3 was reduced to the amine using lithium aluminum hydride to yield hydroxylamine 4.…”

“…The synthetic strategy involved preparing compound 7 , a labeled diamine intermediate that can be elaborated to either EDC or EDU, from commercially available [1,2‐ 13 C 2 ] ethylene glycol 1 (Scheme 1). The first steps of the synthesis were based on the known synthesis of [D 6 ] 3‐dimethylaminopropyl alcohol 5 . Compound 1 was heated with phosphorous tribromide to give bromoethanol 2 in 63% yield.…”