Synthesis of Tris[2‐(dimethylamino)ethyl]amine with Regiospecific Deuterium Labels

Simple synthetic routes to regioselectively deuterated tris[2-(dimethylamino)ethyl]amine (Me6TREN) variants are described. Imine formation with formaldehyde-d2 from tris(2-aminoethyl)amine (TREN) and subsequent reductions NaBD4 afforded N[CH2CH2N(CD3)2]3 or d18-Me6TREN in 79 % yield. A trisubstitution protocol 2-bromo-N,N-dimethylacetamide ammonium carbonate reduction of the N(CH2CONMe2)3 intermediate by lithium aluminum deuteride has N[CH2CD2N(CH3)2]3 (d6-arm)-Me6TREN three steps 52 overall similar 2-bromo-N,N-dimethyl-d2-acetamide, obtained two d4-acetic acid, N(CD2CONMe2)3 hydride N[CD2CH2N(CH3)2]3 (d6-cap)-Me6TREN four 13 yield CD3COOD.