DE1643459B2 - 1- (2-METHOXYPHENOXY) -3-TERT.-BUTYL-AMINO-2-PROPANOL AND ITS SALT, PROCESS FOR THE PREPARATION AND MEDICINAL PRODUCT - Google Patents

Description

OCH,

OCH ₁ -CH-CH ₂ -NH-IC ₁ H ₄

OH

The invention relates to that as defined in the claims. Objects.

In the last minute! Attention has focused heavily on the manufacture of pharmacologically active compounds concentrated, which is a // - adrenergic Have an inhibiting or blocking effect. This effect is generally of great value in treatment of angina and in the control of cardiac arrhythmia as well as to reduce certain Forms of obstruction of the arteries leading away from the heart in congenital and acquired Heart damage.

Albeit extensive research aimed at discovering a useful one ί-adrenergic inhibitor, yet the remedies produced so far are either a high degree of effectiveness in suppressing the acceleration of the pulse caused by isoproterenol is brought about, owns. Furthermore, it shows no noticeable effect on the normal mean Blood pressure, however, exhibits dose-related inhibition of antihypertensive drugs Response to isoproterenol. They also have a low toxicity.

The superiority comes from the following test report emerged:

Anesthetized dogs were used as test animals for the experiments. These were stimulated with isoproterenol. The i-blocker to be tested was then given intravenously. The table shows the amount of the Active ingredient was necessary to increase the heartbeat and blood pressure caused by Isoproterenol had been caused to block.

Tested connection

, · (- blocker effect
HD ₅ ,, Img kg)

toxicity
LD ₅ "(mg.kg)

Heartbeat blood pressure oral inlrapcri-

loneal

- 9 - CH ₂ - CH - CH ₂ - NHCH (CHj) ₂

■ HCl
(Propranolol)

0.028 *) 0.041 368

! 14

OCH,

HC

O --- CH ₂ - CH - CH ₂ - NHC (CH,!,

OH
(compound according to the invention)

0.012 *) 0.039 420

168

♦ ι MiHrI from? Compared

The compound of the present invention can be conveniently prepared by treating 1- (2-methoxyphenoxy) -3-halo-2-propanol with tertiary butylamine. The time taken to carry out the reaction, as indicated in the examples, is not binding as longer periods of time can be used provided that it does not result in undue decomposition of the starting materials or the product. However, a satisfactory shorter period of time can also be determined by periodic analysis for ionically bound chlorine in the reaction mixture. The reaction can be carried out at temperatures from about room temperature to about 150 ° C, although the preferred Umsetzungstemperatui is about 100 ⁰ C. Even if the example uses a large excess of tert-butylamine without a solvent, a smaller amount of amine can advantageously be used in the presence of an inert solvent, e.g. By using an equivalent of the amine in an alkanol such as ethanol, which enables the immediate isolation of the hydrohalide of the product by diluting the reaction mixture with ether.

The amine formed can according to known Me-:> methods are isolated; such a method is described in the example. However, it is preferred that To isolate amine as a pharmaceutically acceptable acid addition salt. Albeit the preferred method to prepare the acid addition salts with aqueous acid, they can just as well, for example with alcoholic acid or by treating a solution of the free base in an inert solvent, like ether, with an anhydrous acid. 7. B hydrogen chloride.

The following example explains the invention.

example

1- (2-Methoxyphenoxy) -3-tert-butylamino-2-propanol hydrochloride

A. l- (2-Methoxyphenoxy) -3-tert-butylamino-

2-propanol

A mixture of 52.4 g of 1- (2-methoxyphenoxy) -3-chloro-2-propanol is kept and 65 g of tert-butylamine on a steam bath under reflux for 116 hours, during which time the mixture turns yellow with the formation of solids. You acidify with 250 ml of 6N hydrochloric acid, extracted several times with diethyl ether, the ether extracts washed several times with water, make the combined aqueous extracts basic with dilute sodium hydroxide solution and extracted them four times with diethyl ether, then washed the combined ether extracts several times with water and evaporates to dryness. 52.6 g of l- (o-methoxyphenoxy) - 3 - tert are obtained. - butylamino - 2 - propanol as Solid.

B. l- (2-methoxyphenoxy) -3-iert.-butylamino-

2-propanol hydrochloride

The solid product obtained according to A is dissolved in 60 ml of 4N hydrochloric acid, evaporated to dryness and the dried solid is recrystallized from ethanol-diethyl ether. 48.1 g of 1- (2-methoxyphenoxy) -3-terl are obtained. - butylamino - 2 - propanol -. Hydrochloride, mp 140-142 ⁰ C. Further recrystallization from ethanol-diethyl ether gives an analytical sample, melting at 142-143 ° C.

Analysis door C ₁₄ H ₂₄ ClNO ₃ :

Calculated ... C 58.02, H 8.35. N 4.83%;
found .... C 57.78, H 8.19. N 4.85%.

Claims (3)

Patent claims: 1. 1- (2-Methoxyphenoxy) -3-tert-butylamino-2-propanol and its pharmaceutically acceptable acid addition salts. 2. Process for the preparation of the compound according to claim 1, characterized in that l- (2-methoxyphenoxy) -3-halo-2-propanol with tert-butylamine is used in a manner known per se reacted and optionally treated the base formed with an appropriate acid. 3. Medicament containing a compound according to claim 1 as an active ingredient. poor in pharmacological activity, "or because they are toxic or otherwise undesirable Have side effects and thus their pharmaceutical dosage and general applicability is restricted. There is therefore a continuing need for effective / i-receptor blockers. It has now been found that the 1 - (2 - methoxyphenoxy) - 3 - tert according to the invention. - butylamino - 2 - propanol the formula!