SU634668A3 - Method of obtaining heterocyclic compounds - Google Patents

Description

(Н2§В21 Н, Нз (-7 CH BiNHg етг where В, and В have the indicated meanings. Example. Triple N-2 hydrochloride N-2 (4-methyl-5-imidazolipmegylthio) -ethyl - N- {2- (4 methyl-5 -imidazolylmethylthio) propyl guanidine A. A solution of 14.8 g of 4-hydroxymethyl-5-methylimidazole hydrochloride 12.8 g of 2-mercaptopropylamine hydrochloride in 1OO ml of 48% aqueous hydrobromic acid is heated at reflux temperature for 6 h , concentrated and recaptured from a mixture of ethanol and ether to obtain 30.0 g of double bromo-yyrate 2 (4 methyl-5-.-imidazolylmethylthio) propylamine, t, n 177-178 C. B. A solution of 2.29 g of N (5-methyl-4-imidazolylmethylthio) ethyl thiourea and 1.56 g of methyl iodide in 5 ml of methanol is kept at room temperature for 18 hours, obtained at BTO 2 , 3 g of S -methyl-M- 2- (5-methyl-4-imide solnemethylthio) ethyl tyuronium iodide, mp 128-131 C, are converted to the corresponding sulfate by ion exchange on an ion-exchange resin 1R A 4O1 in the sulfate form. B, Solution of 4.0 g of 2- (4-methyl-4-imidazolylmethylthio) propylamine (from dihydrobromide) and 3.35 g of S-methyl-N-J2 (4-methyl-5-imidazolyl) methylthio ethyl thiuronium sulfate in 25 ml of water is heated at a temperature of reflux with reflux for 4 hours. Concentration followed by purification on ion exchange resin Q50 (H with evacuation of 0.02 n hydrochloric acid, treatment with sodium hydroxide and picrolic acid gives 1.75 g of ternary picrolonate N - 2 - (4-methyl 5-imidazolylmethyltrope) propyl} guanidine m.p., 173-175 C, from aqueous dimethylformamide. Found,%: With 46.9; H 4.5; N21.9; & 5.1. 8.60 imidazole - 2H: singlet, and 3.94 imidazole - CHP: singlet. C ,, H ,, N, S,. calculated,%: C 47.1; H 4.4; N22.7 S 5.5. Triple pikrolokT suspended in aqueous ethanol and treated with hydrochloric acid to form the corresponding ternary hydrochloric salt, Found,%: CE 22.1; lg a-znse. Calculated,%: CE 21.7. PRI me R 2, Triple hydrochloride H, N-bis f2 -. (4-methyl-5-imidazolylmethyl) propyl} guanide raa. A. A solution of 13.0 g, 2- (4-methyl-5-imidazolylmethylthio) propylamine (from dihydrobromide) in 50 ml of ethanol is cooled to 0 ° C and 3.78 g of benzoylminoesulformethane are stirred during the gradual addition. After the addition, the reaction mixture is left to stand at room temperature for 2 hours and heated on the steam bath for 30 minutes. The mixture is then poured into water and the undissolved material is removed by filtration, the pH of the filtrate is adjusted to 9. The resulting crude product is purified by chromatography on an alumina column, followed by chromatographic purification on a sklikagel column (chloroform / methanol) to give N - benzoyl-NSN-bis-2- {4-methyl-5-imidazolylmethylthio) propyl -guanidine. B. 3.2 g of benzoyl compound is then hydrolyzed in 40 ml of concentrated hydrochloric acid at a steam bath temperature for 5 hours. After cooling, diluting with water and extracting with ether to remove benzoic acid, the product is purified as in Example 1 and concentrated to obtain 1.35 g of picrolonate t, pl. 230 ° C (decomposed). The picrolonate is dissolved in aqueous methanol, purified by an IF A 401 ion exchange resin (C6) and acidified with hydrochloric acid to form the guanidine N, N-bis-2- (4 methyl-5-imidazolylthio) propyl hydrochloride. The NMR spectrum of the solution in L.O. is cleared at 1OO MHz and contains the following chemical shifts: (2.0 protons on the integral curve, calculated for 2.0 protons), (4.4 protons on the integral curve, calculated for 4, 0 protonOB),, with

where B and Bg are the higher alkyl groups, so that the sludge is (CH) 2, and B- is

CH3 -CH2-CH-m - (jH-dH -,

CHj

or B and B.g both% 1 are taken from

-CHN-CH-CH-CHL- ,. II

sn,

CH,

five

characterized in that the dilation of the general formula

HjC-77GH2 $ BiUH-

SA UffU

СН2 $ В, ЖН- (С.

Hf

v

where B and Bg have the indicated meanings;

A is a lower alknp and is reacted with a common amine foil with the corresponding amine.

H, (- 7

3 SchuK nn w

or

fijtJ-7 Y 5H2 $ BiKH2 3®NK K

where B and B have specified captures.

Sources of data taken into account during the examination:

38 1, Weigand - Hilgetag. Metopy experiment in organic khmnvn. M., 1968, p. 512. NH-CHR-: doublet, (f 3.39 (6.6 protons on the integral Oi / -e el. About r-.1 curve, calculated at 6.0 CHO-CH - S: multiplet, cr 3, 04, J protons), imidazole — CH „: singlet, cf 2.37 {6.0 protons on the integral –CH–: doublet, d 1.34. SN o ormula of the invention. Method of obtaining heterocyclic tg dinene of the general formula Hjd / - СНзSBi: NH - (- HHB2 cw y-yn, –v --V -11f w curve, internal standardg), Tn