SU498906A3 - Method for preparing indazole derivatives - Google Patents

Description

(54) METHOD FOR OBTAINING DERIVATIVES OF INDAZOL

one

This invention relates to a process for the preparation of indazole derivatives of the general formula

where RI is hydrogen or Ci-C3-alkyl;

R2 is hydrogen, halogen, or alkyl, alkoxy or alkylthiorue with 1-3 carbon atoms;

Кз - hydrogen, halogen, alkyl or adkoxygroup with 1-3 carbon atoms or hydroxy group;

A - di - or trimethylene, in which one hydrogen atom can be replaced by hydroxyl or C-C3 alkyl, which have physiological activity.

Compounds of this formula may be in tautomeric form.

ten

The proposed method for the preparation of these compounds is based on a known reaction and is concluded in that the compound of the general formula

20

NH2-A-)

25

where RI, Kr, Rs and A are as defined above, they undergo cyclization and the desired products are isolated by known methods.

The cyclization is usually carried out in an inert solvent, preferably in C-C alcohol, for example ethanol, in water, dimethylformamide T1ri 20-150, preferably at 60-110 ° C, in the presence of bases, for example alkali metal or alkaline earth metal hydroxide, or heavy metals such as mercuric oxide or lead acetate.

For the synthesis of starting compounds of a compound of the general formula

where RI, R2, and Rs - KaiK indicated above, is treated with thiaphosgene, preferably in 3 n. hydrochloric acid at room temperature, followed by the reaction of the resulting 7-isothiocyanatoindazols with compounds of the general formula

iNHs-A-NH2,

where A is as defined above, in an inert solvent, such as chloroform, at room temperature.

The resulting target products are at room temperature. Peratura solids are crystalline or oily substances that can be treated with orthanic or inorganic acids and converted to acid crystallizing acid-a-dative salts. As acids, hydrohalic acids, sulfuric, phosphoric, toluenesulfonic, acetic, malonic, succinic, block, maleic and tartaric acids are commonly used.

Example. 7- (Imidazolin-2-ylamiio) - methylindazole. 10 g of N- (2-aminoethyl) -M (1-methylindazolyl-7) -thiourea are added to a solution of 2.3 g of potassium hydroxide in 30 ml of ethanol, boiled for 15 hours under reflux, acidified with concentrated hydrochloric acid and evaporated. The residue is dissolved in 150 ml of 4 n. hydrochloric acid, filtered, alkalinized filtrate 2 n. with caustic soda, extracted with 2x100 ml of chloroform, the o-combined organic phases are dried over sodium sulfate, evaporated, the residue is recrystallized from ethyl acetate and the desired product is obtained, t. 1PL. 180-181 ° C

For the synthesis of the starting N- (2-amino-ethyl) N (1-methylindazolyl-7) -thiol Bins to a solution of 20 g of 7-amino-1-methylindazole in

600 ml 3 n. (lOic acid, 24 g of thiofosren is added, stirred for 24 hours at room temperature, a corrosive precipitate is filtered off, washed with water, the residue on the filter is dissolved in a hot form in 1 l of cyclohexane, the undissolved products are filtered, the solution is treated with activated carbon, filtered and evaporated. A light yellow precipitate is recrystallized from CEClohexane to give 1-methyl-7-isothiocyanato-indazole, mp 68 ° C.

A solution of 19 g of 1-methyl-7-isothiocyanatoindazole in 150 ml of chloroform is added dropwise to a mixture of 30 ml of ethylenediamine and 200 ml of chloroform, stirred for 20 hours, the precipitate is filtered off, the filtrate is evaporated and the oil is separated, which gradually crystallizes. The crystals are suspended in 400 ml of boi; after 1 hour they are filtered; a white residue of an OK-filter is dissolved in an IB 300 ml 4n. hydrochloric acid, filtered, shaken the filtrate twice with 300 adl chloroform, alkalinized 2 n. caustic soda and extracted with 2x300 ml of chloroform. The chloroform extracts are combined, evaporated, the residue is recrystallized from ethyl acetate and the N- (2-amino-ethyl) -N- (1-methylthylenazole-7) -thiourea is isolated, m.p. 153 ° C.

The compounds listed in the table are prepared similarly.

Claims (1)

Invention Formula The method of obtaining derivatives indazole of general formula ten where iR is hydrogen or Ci-Cz-alkyl; R2 is hydrogen, halogen or alkyl, alkoxy or alkylthio with 1-3 carbon atoms; Cs is a common, halogen, alkyl or alkoxy group with 1–3 carbon atoms or oxy group; A is di- or trimethyl-ene, in which one hydrogen atom can 1 be substituted with hydroxyl or Ci-Cz-alkyl, differing from the fact that the compound of the general formula I H A-XH-C-S where RI, R2, Rs and A have the above value, is subjected to cyclization with the selection of the target product known methods.