JPS58225074A - Dibenzoazepine derivative - Google Patents

Abstract

NEW MATERIAL:The compound of formula I [R<1> is H or one or more substituent groups (halogen, lower alkykoxy or lower alkyl); the group of formula II is group of formula III (R<4> and R<5> are lower alkyl or form together with N a heterocyclic group; m is 2 or 3), 4-methylpiperazinyl or 4-methylhomopiperazinyl] and its salt. EXAMPLE:2, 4-Diisopropyldibenz[b, f][1, 4]oxazepin-11(10H)one-8-carboxylic acid N-methylpiperazinamide. USE:Antiulcer agent. PROCESS:The compound of formula I can be prepared easily by reacting the dibenzoxazepinonecarboxylic acid of formula IV or its reactive derivative (e.g. acid halide, and anhydride, ester, etc.) with the compound of formula V.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is based on the following general formula (wherein R1 is a hydrogen atom, a halogen atom, a lower alkoxy group, a lower alkyl group).
- methylpiperazinyl, 4-methylhomopiperazinyl group, R and R are lower alkyl groups, respectively, and may be bonded to each other to form a complex with a nitrogen atom, and m is 2 to 3'e ftt+ and its salts.

The compound of the present invention represented by the above formula is, for example, a compound of the general formula (in which R' has the same meaning as above), in which dipenzoxazepinonecarboxylic acid has the same meaning as above). It can be easily obtained by reacting with a compound. Examples of the reactive conductor here include acid halides, acid anhydrides, and esters.

This reaction uses acetone, benzene, tetrahydrofuran, dioxin, and chloroform as thermal solvents.

F [When used in a solvent such as ethyl, N, N-dimethylformamide, water, etc., or in a mixture thereof, in the presence of a dehydrating agent or a condensing agent, or in the acid halide state, , in the presence or absence of a dehydrohalogenating agent, under cooling, at room temperature, or by heating.

Examples of the dehydrating agent here include carbodiimides such as N,N'-dicyclohexylcarbodiimide,
Examples of condensing agents include phosphorus oxychloride.

Thionyl chloride, phosgene, etc., and dehydrohalogenation agents include, for example, sodium hydrogen carbonate.

It is preferable to use potassium hydrogen carbonate, sodium carbonate, potassium carbonate, sodium hydroxide, triethylamine, pyridine, etc.The reaction time varies mainly depending on the reaction temperature and the type of reagent used, but it is instantaneous to about 10 hours. be.

The compound of the present invention thus obtained has excellent antiulcer activity and is useful as a medicine.

Example 1 8-carboxy-2,4-diisopropyldipenzo (b
, f] [1,4) Oxazepine-11 (IOH) on 3
．． 4tf was dissolved in 25ml of dry benzene, and 10ml of thionyl chloride was added thereto and refluxed for 3 hours.

After the reaction, the excess thionyl chloride 'tM is distilled off under pressure to give the carboxylic acid chloride as an oily residue. This is dissolved in 30me of chloroform and added dropwise with stirring to an ice-cold mixture of 3v of N-methylbiperazine and 10% NaOH15*e. The chloroform layer was stirred for 1 hour under water cooling and then for 2 hours at room temperature, the chloroform layer was washed with water 4 times, the dry ridge solvent was distilled off, and 2,4-diisopropyldipenzo (b
, f) [1,4]oxazepine-11 (IOH) on 8
-Carboxylic acid N-methylpiperazine amide 3.6 f
'Iz get it. Yield 85.4%, recrystallized from benzene-hexane, melting point 191-2°C. A hydrochloride salt having a melting point of 285-8°C (decomposition) is obtained from 10% ethanol hydrochloric acid.

Elemental analysis value OHN as molecular formula 026H3103N3 Theoretical value (3) 71.23 7.41 9.97 Actual value) 71.21 7.39 9.85 Example 2゜8-Carboxydipenzo (b, r) ( 1,t) Oxazepi:/-11(IOH)on 2.0? 'fr: Dissolve in 35d of dry N,N-dimethylformamide, add 1.1 rnl of triethylamine, add 0.94f'i of ethyl chlorocarbonate dropwise at -7°C, then add 0.94f'i of N-methylpiperazine. Add 8 mef below -5°C and stir at 0°C for 1 hour. Muroya 9 - Pour into 200ml of drained water that was left overnight, and remove the precipitate with chloro; ULAr - 0
．． ．． The residue is subjected to silica gel chromatography.

Dipenzo (b,
r) (x,4)Oxazepi/-11(IOH)oncerboxylic acid N-methylpiperazine amitohego 92 is obtained. Yield 28.7%, recrystallized from benzene-hexane, melting point 20
A hydrochloride salt is obtained in the same manner as in Example 1 at 1-2°C.

Melting point: 251°C (decomposed).

Elemental analysis value Molecular formula 019I (OH as IJO3N3
N Theoretical value (1) 67.46 5.68 12.46 Actual value) 67.52 5.58 12.35 Example 3~
10゜ Compounds of Table I in the same manner as in Example 1 or Example 2 Continued from page 1 of Q Multiple Examples Author: Tamotsu Yamazaki Chugai Pharmaceutical Co., Ltd., 3-41-8 Takada, Toshima-ku, Tokyo 0 Inventor: Sakai - Chugai Pharmaceutical Co., Ltd., 3-41-8 Takada, Toshima-ku, Tokyo Inventor: Toshi Hata - Chugai Pharmaceutical Co., Ltd., 3-41-8 Takada, Toshima-ku, Tokyo Inventor: Yoshio Takagaki Toshima-ku, Tokyo 3-41-8 Takada Chugai Pharmaceutical Co., Ltd.

Claims (1)

[Claims] General formula (wherein R1 means 1 to piperazinyl group selected from a hydrogen atom or a halogen atom, a lower alkoxy group, a lower alkyl group, and R4 and FLS are each a lower alkyl group or a bond with each other) may form a heterocycle together with a nitrogen atom, and the compound represented by the formula (2 or 3) and its salt.