"Azetidinyl-Tryptamine", or 3-(N-Azetidinyl-ethyl)-Indole is a DMT analog, where the two N-methyl groups are connected with a -CH
2- group to form a four-membered ring, an azetidine. The compound can be thought of as a conformationally restricted analog of DMT and a cyclic isomer of N-Methyl-N-Ethyl-Tryptamine (Why can I not find the latter in Tihkal?). It is most certainly active, and I find it to be a
very worthwhile synthetic target. Who will be the first to prove that it is active (perhaps even orally so)?
4-(1-Azetidinyl)butanal dimethylacetalA mixture of azetidine (2.0 g, 35.0 mmol), 4-chlorobutanal dimethylacetal (5.88 g, 39.0 mmol) and K2CO3 (5.38 g, 39.0 mmol), in anhydrous DMF (100ml), was stirred at room temperature for 72 h. Water (50 ml) was added and the mixture extracted with EtOAc (3x150 ml). The combined extracts were washed with 3x50ml H2O, dried (Na2SO4) and evaporated. The crude product was purified by distillation (1.2 g).
3-indolyl-ethylazetidine (Hydrogen Oxalate Hemihydrate)A solution of substituted phenylhydrazine (4.1 mmol) and 4-(1-azetidinyl)butanal dimethylacetal (0.65 g, 3.8 mmol), in 4% H2SO4 (30 ml), was refluxed for 4.5 h. The solution was cooled to room temperature, basified with K2CO3 and extracted with EtOAc (4x100 ml). The combined extracts were dried (Na2SO4) and evaporated and the residue chromatographed on silica-gel eluting with CH2Cl2/MeOH/NH3 (40:8:1) to give the title indole. The hydrogen oxalate hemihydrate salt was prepared (30 mg).
Reference:
Patent US5567726