DE1620347C3 - Process for the production of 5- (dialkyl-aminoalkyl) -5, l 1-dihydrodibenz square bracket to b, square bracket to square bracket to 1,4 square bracket to oxazepines - Google Patents

Description

in which R and R 'are each hydrogen, halogen, low molecular weight alkyl or alkoxy, trifluoromethyl, Trifluoromethylmercapto, trifluoromethoxy or N, N-dimethylaminosulphonyl groups and A is a low molecular weight alkylene group at least 2 carbon atoms and B a low molecular weight dialkylamino radical with at most 12 carbon atoms mean by reaction of a 5,11-dihydrodibenz [b, e] [l, 4] oxazepine of the general formula II

NH- A

-j-R (H)

- o - \ y

30th

in which R and R 'have the meanings given above, with a dialkylaminoalkyl halide of the general formula III

B - A - halogen (Hl)

in which A and B have the meanings given above, in the presence of a basic condensing agent and in a solvent, characterized in that the reaction in the presence of an excess of powdered sodium hydroxide in acetone.

It is known that 5- (aminoalkyl) -5, ll-dihydrobenzoxazepine have physiological effectiveness. In U.S. Patent 3,069,432 there are such Compounds and a process for their preparation are described.

The known process is carried out in the presence of a basic condensing agent such as sodium hydride, and in the presence of a solvent, e.g. B. xylene performed. From Journal of Medicinal Chemistry, Vol. 7 (1964), pp. 609 to 614, it is also known, the condensation with sodium hydride in dimethyl sulfoxide or tetrahydrofuran to carry out.

It has now been found that the yield of the desired products compared to that after known processes, the yield obtained can be increased significantly in a reproducible manner, if you use acetone as a solvent, and that you use the difficult to handle, to spontaneous combustion The tendency to replace sodium hydride with the cheaper and safe sodium hydroxide.

It is surprising that in the process according to the invention with the relatively reactive Solvent acetone, which is less flammable than xylene because it is miscible with water Alkylation can carry out successfully and with more favorable yields. It is known that acetone is present in The presence of strong bases condenses to form diacetone alcohol.

Preferably, the powdered sodium hydroxide is used in an excess of at least about 4 molar equivalents, and more preferably from about 6 to 8 molar equivalents per mole of that in the reaction mixture present compound of formula II used. Although the reactants of the general formulas II and III can be used in stoichiometric amounts, the amine is the general Formula III is preferably used in excess in order to ensure complete conversion.

The reaction can take place at normal temperature, e.g. B. room temperature can be carried out. Preferably but it is at elevated temperature, for. B. at the reflux temperature of the reaction mixture carried out, to increase the reaction speed.

The examples explain the process according to the invention.

example 1

Production of

5- (2-dimethylaminoethyl) -5, ll-dihydrodibenz [b, e] [l, 4] oxazepine maleate

A mixture of 10 g of 5,11-dihydrodibenz [b, e] - [l, 4] oxazepine, 24 ml of 2-dimethylaminoethyl chloride and 16 g of powdered sodium hydroxide in 100 ml Acetone is refluxed for 2 hours. The mixture is cooled, filtered and evaporated Filtrate to dryness. The residue is dissolved in ether and extracted with dilute hydrochloric acid.

The acid phase is made alkaline with sodium hydroxide solution and extracted with ether. The ethereal solution is then concentrated, the residue is dissolved in acetone and a solution of Maleic acid in acetone to it. After the addition of ether, the product crystallizes out and is obtained in 72% yield 5- (2-dimethylaminoethyl) -5,11 -dihydrodibenz [b, e] [1,4] oxazepine maleate, melting point 141

up to 142 ° C.

If the above example is carried out for comparison with tetrahydrofuran instead of acetone, so the yield drops to 39%.

In the procedure of Example 12 of U.S. Patent 3,069,432, the yield is on use of xylene 28%.

55

Example 2

Production of ·

5- (2-Dimethylaminoethyl) -5,11 -dihydro-7- (trifluoromethyl) -dibenz [b, e] [ 1,4] oxazepine maleate

A mixture of 5 g of 5, ll-dihydro-7- (trifluoromethyl) -dibenz [b, e] [l, 4] oxazepine, 8.2 g of 2-dimethylaminoethyl chloride and 6 g of powdered sodium hydroxide in 50 ml of acetone is reacted according to Example I and gives 5- (2-dimethylaminoethyl) -5, l in a 64% yield 1 -dihydro-T-itrifiuormethyO-dibenz-

. [b, e] [1,4] oxazcpine malcat; Mp 166-168 ° C.

Example 3

Production of

5- (2-Diethylaminoethyl) -5,11 -dihydro-7- (trifluoromethyl) -dibenz [b, e] [1,4] oxazepine maleate

A mixture of 7.3 g of 5, ll-dihydro-7- (trifluoromethyl) -dibenz [b, e] [l, 4] oxazepine, 15.0 g of 2-diethylaminoethyl chloride and 8.8 g of powdered sodium hydroxide in 73 ml of acetone is reacted according to Example 1 and gives 5- (2-diethylaminoethyl) -5, l in 80% yield 1 -dihydro-7- (trifluoromethyl) -dibenz- [b, e] [l, 4] oxazepine, Bp. 152 to 157 ° C / 0.2mm. The maleate of this base melts at 147 to 149 ° C.

Claims (1)

Claim: Process for the preparation of 5- (dialkylaminoalk'yl) -5, ll-dihydrodibenz [b, e] [l, 4] oxazepinender general formula I. IO R (I)