Amido, aminoamido, and diamino groups in combination with various aromatic and heterocyclic systems are the most widely encountered pharmacophore ~ents in antiarrhythmic drugs [1]. Arylalkyl structures are known to exhibit psychotropic activity as well [2,3]. In continuation of our previous search for new drugs possessing these properties [4], we have synthesized substituted aminoamides and diamines representing 4-spyrosubstituted 1,2,3,4-tetrahydroisoquinolines (X, XII) and their analogs (XI, XIII) as described in the scheme below.The initial compounds were 4-spyrosubstituted 6,7-dimethoxy-l,2,3,4-tetrahydroisoquinolines (I, II) [4,5] or [1-(3,4-dimethoxyphenyl)ethyl]methylamine (IH) [6]. Acylation of amines I -III by chloroacetic chloroanhydride (IV) in the presence of pyridine led to N-chloroacetyl derivatives (V-VII) obtained under the optimum reaction conditions (0 to -2~ with a yield exceeding 70%. Aminoamides X and XI were synthesized by heating toluene solutions of the corresponding chlorine-containing derivatives of V-VII and amine III, piperidine (VIII), or morpholine (IX) on a boiling water bath in sealed ampules in the presence of catalytic amounts of potassium iodide.A comparison of the IR spectra of chloramides V-VII with those of aminoamides X and XI reveals, as expected, a shift of the absorption band due to the C--O groups toward lower frequencies (from 1650 to 1620 era-l). Note that the passage from bases of aminoamides X to their hydrochlorides is accompanied by a reverse shift of the absorption bands of carbonyl from 1620 to 1670 cm-1. The IH NMR spectra of X and XI, in contrast to those of chlommides V-VII, display new signals at 3.6 -3.8 ppm due to the methylene protons of the morpholine cycle (CH2OCH2) or the signals from methylene protons ofpiperidine in the form of a broad singlet 403 at 1.6 -1.8 ppm (CH2CH2CH2) and 3.8 -4.2 ppm (CH2NCH2).Aminoamides X and XI were reduced by lithium aluminum hydride to the corresponding diamines XII and XIII. The structures of products were established by spectroscopic techniques, in particular, by comparing the ltL IH NMR, and mass spectra of amides X, XI and diamines XII, XIII.
EXPERIMENTAL CHEMICAL PARTThe IR spectra were measured on an UR-20 spectrophotometer (Germany) using samples prepared as vaseline oil suspensions. The 1H NMR spectra were obtained on a Varian T-60 spectrometer (USA) using TMS as the internal standard. The mass spectra were measured on an MX-1320 spectrometer. TLC chromatograms were obtained on A1203 plates of activity type II, eluted with a benzene-acetone (4: I) mixture. Hydrocb_lorides were purified by recrystallization from acetone. The melting temperatures were determined on a Boetius heating stage (Germany). The data of elemental analyses for C, H, N, and C1 agree with the results of analytical calculations performed for the empirical formulas.6,7-Dimethoxy-2-chloroaeetyl-l,2,3,4-tetrahydroisoq uiuo-line-4-spyro-4'-tetrahydropyran (V). To a mixture of 5.6 g (0.05 mole) of chloroanhydride IV with 50 ml of benzene at-2 -0~ was...
