IE46732B1

IE46732B1 - N-(2-(3,4-dialkoxyphenyl)ethyl)-3,4-dialkoxyphenylacetamides

Info

Publication number: IE46732B1
Application number: IE2296/81A
Authority: IE
Original assignee: Sobio Lab
Priority date: 1978-04-20
Filing date: 1978-04-20
Publication date: 1983-09-07
Also published as: IE780779L; IE812296L; IE46731B1

Description

This invention relates to a class of amides which are useful as intermediates for preparing hydrogenated benzylisoguinoline derivatives which possess spasmolytic and hypotensive activity.

Patent Specification No. 46731 discloses compounds of formula (II), or a pharmaceutically acceptable acid addition salt thereof: (II) 'Γ 2 wherein R and R are different and one represents a Gj.'-Gg alkyl group and the other represents a C^-Cg alkyl group; and A and B either both represent hydrogen or together represent a covalent bond.

The compounds of formula (II) may be prepared by a process which comprises (a) cyclisation of a compound of formula (IV): (IV) OR OR with a condensing agent (to produce a compound of formula (II) in which A and B together represent a bond); and (b) optionally reducing the resultant product (to produce a compound of formula (II) in which A and B are both hydrogen).

The present invention provides an amide of 1 2 formula (IV) wherein R and R are as defined with respect to formula (II) above, with the proviso that, 2 when one. of R and R is propyl, the other is not C.-C3 alkyl.

The groups R^ and R^ may be, for example ethyl, n- or iso-propyl, or η-, iso-, sec- or tert -butyl, subject to the foregoing proviso. Preferably, one of 1 2 R and R represents isopropyl.

The compounds according to this invention may be prepared by known methods for preparing amides, for example by reacting a phenylethylanine of formula (V) with a compound of formula (VI): (VI) wherein Y represents a carboxylic acid group or an ester thereof, preferably an ethyl ester and R1 and R are as defined as above. This reaction is conveniently carried out without solvent at a temperature of from 12O°-21O°c.

The compounds of the present invention may be prepared by analogy with the following Examples: Example 1 n-/2-(3,4-diethoxyphenyl)ethyl7-3,4diisopropoxyphenylacetamide A mixture of 2 - (3,4 - diethoxyphenyl) - ethylamine (40«7g), 0.195 mole) and ethyl 3,4 - diisopropoxyphenyl - acetate (55.7 g, 0.195 mole) was heated with stirring at 160°C for 20 hours, allowed to cool and the resulting oil taken up in 700 ml of chloroform. The organic solution was washed 3 times with 100 ml of N hydrochloric acid and then with water to pH 7. The chloroform solution was dried over magnesium sulphate, the solvent removed under reduced pressure and purification effected by chromatography over silica gel, 64.5 g (yield 72%) of product was obtained sufficiently pure to be used in step (b) below.

By recrystallisation of a sample of cyclohexane N - /2-(3,4 - diethoxyphenyl) ethylj7 - 3,4 - diisopropoxyphenylacetamide is obtained, m.p.=37°C.

Analysis C2 gH, 71:0^-443.6 C% K% Calculated 70.40 8.41 3.16 Pound 70.49 8.22 3.13 Example 2 11-/2-(3,4-Diisopropoxyphenyl)ethyl/-3, 4diethoxyphenylacetamide N - /2 - (3,4- Diisopropoxyphenyl)ethyl7 3,4 - diethoxyphenylacetamide was prepared starting from 2 - (3,4 - diisoproxyphenyi)ethylamine and ethyl 3,4 diethoxyphenyl acetate using the process described in Example 1.

Yield=67%, m.p. 71°C. Analysis ^6^37^5^43.6 C% N% Calculated 70.40 8.41 3.16 Found 70.73 8.09 3.07 Example 3 N-/2-(3,4-diethoxyphenyl)ethyl/~3,4-di-npropoxyphenylacetamide N - j/ί - (3,4 - diethoxyphenyl)ethyl - 3,4 di - n - propoxyphenylacetamide was prepared from 2 (3,4 - diethoxyphenyl)ethylamine and ethyl 3,4 - di n - propoxyphenyl acetate using the process described in Example 1. - 6 Yield=77.5%, m.p. 99°C Analysis C Β,Λ=443.6 26 37 5 C% HS NS Calculated 70.40 8.41 3.16 5 Pound 70.20 8.37 3.20 Example 4 N-/2-(3,4-di-&-propoxyphenyl)ethyl/7-3,4diethoxyphenylacetamide N-/2- (3,4 -di -n- propoxyphenyl)ethyl7 10 3,4 - diethoxyphenylacetamide was prepared from 2 (3,4 - di - n - propoxyphenyl)ethylamine and ethyl 3,4 “ - diethoxyphenylacetate using the process described in Example 1.

Claims

1. CLAIMS;1. An amide of formula (IV): 1 2 wherein R and R are different and one represents a 5 C 1~ C 6 9 rou P a ud the other represents a C^-C^ alkyl group, with the proviso that, when one of R x and R is propyl, the other is not C^_2 alkyl.

2. A compound as claimed in claim 1 wherein 1 2 either R or R represents isopropyl. 10

3. A process for the prepartion of a compound as claimed in claim 1, which process comprises reacting a phenylethylamine of formula (V) with a compound of formula (VI) : wherein Y represents a carboxylic acid group or an 1 2 ester thereof, and R and R are as defined in claim 1

4. A process as claimed in claim 3 wherein Y represents ethoxycarbonyl.

5. A compound according to claim 1 whenever prepared by a process as claimed in claim 3 or 4.