DD263771A5 - PROCESS FOR PREPARING 2-OXO-5-PHENYL-2,5-DIHYDROFURON-3-YLAMINE - Google Patents

Abstract

The invention relates to a process for the preparation of 2-oxo-5-phenyl-2,5-dihydrofuran-3-ylamines. According to the invention, a compound of formula (II) wherein R1 is carboxy or lower alkoxycarbonyl is prepared by reacting a compound of formula (III) wherein R1 is carboxy or lower alkoxycarbonyl with trans-2-oxo-4-phenyl-but-3-ene is reacted in the presence of an alcohol. Formulas (II) and (III)

Description

6 3 7 71

Process for the preparation of 2-oxo-5-phenyl-2 ₎ 5-dlhydrofuran-3-ylamine The field of application of the invention

The invention relates to a new process for the preparation of 2-oxo-5-phenyl-2,5-dihydrofuran-3-ylamines.

Characteristic of the known state of the art

A method in which anilines are used instead of a compound of formula III is described in J. Org. Chem. 33, 3991 (1968).

Object of the invention

The object of the invention is to provide a novel process for the preparation of 2-oxo-5-phenyl-2,5-dihydro-3'-uranium-3-ylamines, which are useful as intermediates in the synthesis of inhibitors of angiotensin converting enzyme (ACE inhibitors). the formula

S \ ' \ Z / S

I II (S). -N-CH-CH ₂ -CH ₂ -... (I),

wherein R ^{1 is} carboxy and R ^{2 is} carboxy or lower alkoxycarbonyl can be used.

- 2 Explanation of the essence of the invention

The invention has for its object to provide a synthetic route for the preparation of 2-oxo-5-phenyl-2,5-dihydrofuran-3-ylamines of the formula II available as intermediates in a synthesis route for the preparation of ACE inhibitors of Formula I can be used, which is simpler and cheaper than the known methods for preparing such ACE inhibitors.

These and other important objects are achieved by the present invention, according to which the corresponding 2-oxo-5-phenyl-2,5-dihydrofuran-3-ylamines of the formula

wherein R ^{1 is} carboxy or lower alkoxycarbonyl, starting from trans-2-oxo-4-phenyl-but-3-enoic acid are prepared by being condensed with a suitable amine of the formula R-NH 2 (III). In this way the new NRN- (2-oxo-5-phenyl-2,5-dihydrofuran-3-yl) -amines of formula II are obtained.

Above and below, the definitions used have the following meanings:

R is the 2,3,4,5-tetrahydro-lH- [1] benzazepine-2-one-3 (S) -yl-radical, which in the 1-position, ie at the ring nitrogen atom, by R ^l -CH 2 - substituted.

The term "lower" defines groups of up to and including 7 carbon atoms, preferably up to and including 4 carbon atoms, and most preferably with one or two carbon atoms.

53771

Lower alkoxycarbonyl is e.g. Methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl or butoxycarbonyl, such as tert-butoxycarbonyl.

In detail, the process according to the invention for the preparation of compounds II comprises the reaction of an amine of the formula

• 1 ·

ίN (SX ·-NH ₂ (III),

wherein R ^{1 is} carboxy or lower alkoxycarbonyl, with trans-2-oxo-4-phenyl-but-3-enoic acid in the presence of an alcohol, preferably a lower alkanol, especially of ethanol.

embodiment

The invention will be described below for the sake of better understanding by way of some examples, which are only by way of example only), without limiting the scope of the invention. Temperatures are given in degrees centigrade.

Example 1; Preparation of 1-ethoxycarbonylmethyl-3S- [ ( 2-oxo-5S-phenyl-2,5-dihydrofuran-3-yl) amino] -2,3,4,5-tetrahydro-lH- [1] benzazepine-2 -on the formula II

To a solution of 0.935 g (0.0055 mol) of trans-2-oxo-4-phenyl-but-3-enoic acid in 8-10 ml of cold ethanol at 0 ° dropwise with stirring, an ethanolic solution of 1.3g (0.005 1-ethoxycarbonylmethyl-3S-attino-2,3,4,5-tetrahydro-1H-1-benzazepine-2-one. After completion of the addition, the mixture is stirred at 20 ° for 1 hour, then allowed to come to room temperature. After 20-43 hours, the product precipitates and can be filtered off. This gives between 60 and 90% of the desired product, depending on the reaction time and temperature. The product has a melting point of 144-146 ° (crude) or 146-148 ° after recrystallization.

Examples 2-4: Example 1 is repeated with the exception that R ¹ in the compound of the formula III is methoxycarbonyl, tert-butoxycarbonyl or carboxy.

Claims (2)

2 * 377! claims 1. A process for the preparation of a compound of the formula wherein R ^{1 is} carboxy or lower alkoxycarbonyl, characterized by the reaction of a compound of the formula (III) wherein R ^{1 is} carboxy or lower alkoxycarbonyl, with trans-2-oxo-4-phenyl-but-3-enoic acid in the presence of an alcohol. 2. The method according to claim 1, characterized in that l-ethoxycarbonylmethyl-3S - [(2-oxo-5S-phenyl-2,5-dihydrofuran-3-yl) -amino] -2,3,4,5- tetrahydro-lH- [1] benzazepine-2-one. FO 7.4 / GR / cc *