NO123386B - - Google Patents

Description

Procedure for the production of indole derivatives.

The present invention relates to a new process for the production of indole derivatives of the general formula:

where R is hydrogen, halogen, hydroxyl, alkoxy, amino, alkylamino or acylamino with up to 6 carbon atoms, R 2 and R 3 , which may be the same or different, are hydrogen or alkyl with up to 6 carbon atoms, and R^ is hydrogen, halogen , amino, hydroxyl or alkyl with up to 6 carbon atoms.

It is known that 2-methylindole derivatives included in formula I have anti-inflammatory and antipyretic properties. It is time-lier known, e.g. from Belgian Patent Nos. 615,395 and 643-268, to prepare N-aroyl-2-methyl-5-substituted 3-indolyl-lower aliphatic acids and esters thereof by various syntheses of the indole ring and with the introduction of the desired substituents either before or after the ring closure. The present method, however, relates to an economic method in which readily available reactants are used which give a pure product in high yield.

The compounds of formula I are prepared according to the present method by indole-2,3:3'>4'-dihydrothiophenes of the general formula:

12**^ lx

where R , R , R and R are as above, is reduced catalytically. The reaction is illustrated by the following diagram:

The catalytic reaction is suitably carried out at room temperature or by boiling under reflux using Raney nickel in alcohol, a mixture of alcohol and water or in an aqueous solution of sodium bicarbonate.

The hitherto unknown starting compounds of formula II can be suitably prepared according to the invention according to the following reaction scheme:

where R<1>, R<2>, R^ and R^ are as indicated above..

The following example illustrates the preparation of a compound of formula I and of the starting material of formula II, as other compounds of these formulas can be prepared in a similar manner.

Example

Preparation of N-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indolylacetic acid

a) 3.2 g of N'-(p-methoxyphenyl)-N*-(p-chlorobenzoyl)-hydrazine hydrochloride and 2 g of 4-thiophenone-2-carboxylic acid in 15 ml of acetic acid are heated

with stirring at 8o°C for 3 hours. After cooling to room temperature, the reaction mixture is poured into 50 ml of water. The precipitated crystals of [N-(p-chlorobenzoyl)-5-methoxy]-indole-2,3:3',4<*->(2<*->carboxy)-

dihydrothiophene is filtered off, dried in vacuum at 6o°C and re-

is crystallized from tertiary butanol.

b) 3 g of the compound prepared in step a) is added to a suspension of 30 g of Raney nickel in 500 ml of ethanol, and boiled slowly

for 4 hours whereby a reduction takes place with the help of hydrogen adsorbed to the catalyst during its preparation.

After cooling, the reaction mixture is filtered. The clear up-

solution is evaporated in vacuo to dryness. The residue is crystallized from tertiary butanol, and pure N-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indolylacetic acid with a melting point of 151°C is obtained.

in a similar way, N-benzoyl-5-methoxy-2-methyl-3-indolylacetic acid with melting point 172 - 173°C and N-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indolyl-a-propionic acid with melting point 87 - 88°C

be asked.

Claims (1)

Procedure for the preparation of indole derivatives of the general formula: where R is hydrogen, halogen, hydroxyl, alkoxy, amino, alkylamino or acylamino with up to 6 carbon atoms, R<2> and R o, which may be the same or different, are hydrogen or alkyl with up to 6 carbon atoms, and R^ is hydrogen , halogen, amino, hydroxyl or alkyl with up to 6 carbon atoms, characterized in that indole-2,3:34'-dihydrothiophenes of the general formula: 1 2 "3 Ll where R , R , R and R are as above, is reduced catalytically.