US 11,896,670 B2
Synthesis routes to access MDMA prodrugs by using controlled and non-controlled intermediates
Daniel Trachsel, Detligen (CH); Matthias Emanuel Liechti, Oberwil (CH); and Felix Lustenberger, Meggen (CH)
Assigned to Mind Medicine, Inc., New York, NY (US)
Filed by Mind Medicine, Inc., New York, NY (US)
Filed on Aug. 23, 2022, as Appl. No. 17/893,292.
Claims priority of provisional application 63/236,498, filed on Aug. 24, 2021.
Prior Publication US 2023/0066171 A1, Mar. 2, 2023
Int. Cl. A61K 47/54 (2017.01)
CPC A61K 47/542 (2017.08) [A61K 47/545 (2017.08)] 2 Claims
 
1. A method of synthesizing a pharmacological compound substance including the steps of:
performing an aldol condensation on 3,4-dibenzyloxybenzaldehyde to obtain 1-(3,4-Dibenzyloxyphenyl)-2-nitropropene;
dissolving 1-(3,4-Dibenzyloxyphenyl)-2-nitropropene in an inert solvent, adding the solution to a suspension of alane, and obtaining 3,4-Dibenzyloxyamphetamine hydrochloride;
reacting 3,4-Dibenzyloxyamphetamine hydrochloride with an activated lysine derivative to obtain Boc-L-Lys(Boc)-3,4-dibenzyloxyamphetamine;
dissolving Boc-L-Lys(Boc)-3,4-dibenzyloxyamphetamine in a solvent and performing a hydrogenolytic removal of O-benzyl groups to obtain Boc-L-Lys(Boc)-3,4-dihydroxyamphetamine;
O,O′—methylating Boc-L-Lys(Boc)-3,4-dihydroxyamphetamine to obtain Boc-L-Lys(Boc)-3,4-methylenedioxyamphetamine; and
performing a step chosen from the group consisting of
(A) deprotecting Boc-L-Lys(Boc)-3,4-methylenedioxyamphetamine to obtain L-Lys-(R,S)-MDA, and
(B) alkylating an amide nitrogen of Boc-L-Lys(Boc)-3,4-methylenedioxyamphetamine to obtain Boc-L-Lys(Boc)-3,4-methylenedioxymethamphetamine, and deprotecting Boc-L-Lys(Boc)-3,4-methylenedioxymethamphetamine to obtain L-Lys-(R,S)-MDMA.