SU423298A3 - METHOD FOR PRODUCING DERIVATIVES OF 2,6-DIMORFOLIN-8-ALKAKOLAMYNO-PYRIMIDO- [5,4-th '] - Pyrimidine - Google Patents

Description

one

This invention relates to a process for the preparation of new pyrimido-5,4-d-pyrimidine derivatives with valuable pharmacological properties.

Based on the well-known mining reaction, the proposed method for the preparation of the 2, b-dimorpholino-8-alkanolamine pyrimido-5, 4-d-pyrimidine derivatives of the general formula

where A, AI and AO-halo are substituted by alkyl, benzyl or phenyl hydroxy, mercapto or sulfonyl groups, one or two of these radicals being capable of representing a morpholino or alkanol amino group

-NRiRa,

treated with alkanolamine of the general formula

where RI-C is C4-alkyl, Cz-Ce-oxyalkyl or

methoxy-C2-Cz-alkyl; R2-- C4-Sb-hydroxyalkyl, consists in the fact that the compound of the general formula

.one,

HN;

where RI and R2-as indicated above, and / or morpholine, eatsBenpo when heated, for example, to 50-200C. The reaction is carried out in the presence of an acid acceptor in a high boiling solvent, for example, in dimethylformamides, an excess of the starting alkanolamine or morpholine. In some cases, the reaction will speed up the add. Copper salt or the salt of the amine used with the acid are added or they are reacted in a closed vessel.

Example 1. 2,6-Dimorpholino-8-butanol-propanolamine-5, 4-d-pyrimidine.

3.4 g (0.01 mol) of 8-chloro-2,6 - dimorpholpnopyrimido - 5,4-d-pyrimidine (t. Pl. 212-

215 ° C) and 14 g of butanol propanolamine are heated for 1 hour to -140 ° C, the resulting orange solution is poured into 200 ml of water and 3.6 g (81%) of the desired product are recovered, m.p. 160-162 ° C (methanol).

Example 2. 2,6-Dimorpholino-8-butanol / prapanolamine-irimido - 5,4- (i is pyrimidine.

3.5 g (0.01 mol) of 8-ethoxy-2,6-dimorpholino-pyrimidine, 5, 4- pyrimidine (mp 210-213 ° C), 4 g (0.01 mol) of 2.6 -5 dimorpholino-8- (2propoxyethoxy) -pyrimido - 5.4- (i - pyrimidine (t. Bl. 141-142 ° C) or 3.6 g (0.01 mol) of 8-ethylthio-2,6 - dimorpholinopyrimido- The 5.4 th pyrimidine (mp. 215-218 ° C) is heated in each case with 14 g of butanolpronolamine for 2 or 8 hours to 200 ° C and the product is isolated as in Example 1.

The output of 40-60%, so pl. 160-162 ° C (methanol).

The same compound is obtained by the interaction of 8-phenoxy - 2,6 - dimorpholipopyrimido - 5,4-uf - pyrimidine, 8-benzylthio2, 6-dimorpholine-pyrimido - 5,4 - - pyrimidine or 8-ethylsulfonyl-2,6 - dimorpholipopyrimido - 5,4-d - pyrimidine with butanolpropanolamine at 200 ° C.

Example 3. 8-Ethanolhexanol "but - 2,6-dimorpholine-pyrimido - 5,4-d - pyrimidine is obtained from β-chloro-2,6 - dimorpholine-pyrimido - 5,4-th - pyrimidine (t. Pl. 212-215 ° С) and ethanol hexanolamine analogously to example 1. Yield 86%, so pl. 148-149 ° C.

The same compound can be obtained from 8-phenoxy- or 8-benzylthio-2,6-dimorpholine Irimido-5,4-d-pyrimidine and ethanol hexanolamine "180-200 ° C.

Example 4. 8-ethanolpentapolamio-2,6-dimorpholin-pyrimido-5,4-fi-pyrimidine is synthesized, as in example 1, from 8-chloro-2,6. Initial alkanolamine

Methylbutanolamine

Ethanolbutanolamino

Dibutanolamino

Isopropanolpentanol

in

Ethanol tert-butanol.mino

n

Hexanolpentanol.mino

propylamine

4-Oxybutyl-3-.methoxypropylamino

Butylbutanolamine

Propyl butanolamino

Methyl pentanolamino

dimorpholinopyrimido - 5,4-rf - pyrimidine and etapolpeptanolamina.

The yield of 78%, so pl. 137-139 ° C. The same compound is obtained by the interaction of 8-ethylthio- or 8-ethoxy-2,6-dimorpholine-pyrimido - 5,4- - pyrimidine with ethanolpentanolamine at - 180-200 ° C.

Example 5. 8-Ethylbutapolamipo - 2,6-dimorpholipopyrimido - 5,4th - pyrimidine is obtained from 8-chloro-, 8-phenoxy- or 8-benzylthio-2, 6 - dimorpholinopyrimido - 5,4-cf) - pyrimidine and ethylbutanolamine at 140-200 ° C. Example 6. 8-Ethylbutanolamine - 2,6 - dimorpholine pyrimido - 5,4-d - pyrimidine.

3.7 g (0.01 mol) of 8-ethyl-butanolamino-6-chloro-2-morpholipopyrimido-5,4-th pyrimidine (mp. 146-148 ° C) and 12 ml of morpholine are heated for 2 hours with a reflux cooler, to 60 ml of water are added to the orange solution and the desired product is isolated as an oily residue. After settling for some time, it is sucked off, washed with water and dried.

The output of 3.4 g (81%), so pl. 135-137 ° C (isolated from 0.1 and. Hydrochloric acid with 2N ammonia).

The indicated compound can be obtained from 8-ethylbutanolamino-2-morpholino-6-phenoxypyrimido-5,4-rf-pyrimidine, 8-ethylbutanolamino-6-chloro-2-methylthiopyrimido 5, 4-c-pyrimidine or 8-ethylbutanolamino-6 chlorine - 2 - methylsulfonylpyrimido, 4th - pyrimidine and morpholine at

- 200 ° C under pressure.

In examples 7-16, target products are obtained as in example 1, using 8-chloro-2,6-dimorpholinopirimido-5,4-d-pyrimidine and various alkanolamines. The results are shown in the table.

Get my connection

t. pl., C

8 NRiR2

output, %

153-155 161-162 180-182 133-135 197-199 134-136 112-114 144-146 147-149 141-143

Subject invention

Claims (2)

1. A method for producing 2,6-dimorpholino-8-alkanolamine pyrimido-5,4-th pyrimidine derivatives of the general formula where A, AI and A: are substitutable radicals, such as halogen, substituted by alkyl, benzyl or phenyl OXY, mercapto or sulphonyl groups, and one or two of these radicals can mean the morpholino or alkaiolamine group — NRiRa; alkanolamine decomposition of the general formula RV where RI is d-C4-alkyl, Cz-Ce-oxanalkyl or methoxy-C2-Cz-alkyl; R-2-C4-Sb-oxyalkkl, about tl and h and Y and O with the fact that the compound of the general formula where RI and R2 - as indicated above, and / or with morpholine, followed by separation of the target product by known methods. 2. A method according to claim 1, characterized in that the process is carried out at an elevated temperature, preferably at 50-200 ° C.