SU617014A3 - Method of obtaining derivatives of 8b-pyrimidine-aminemethyl-10a-ergoline - Google Patents

Description

(54) METHOD FOR PRODUCING 8 fb-pyrimidine-aminomethyl-10 oC-ergoline

one

The invention relates to a method for producing 8 / -pyrimidinoaminomethyl-10-o-ergrlin derivatives not described in the literature.

gle R is hydrogen or methyl,

R and RJ are hydrogen, methyl or phenyl, Rj is hydrogen, halogen, methoxy, phenyl,

nitro, amino, or cyano circle having

pharmacological activity.

The known method is obtained (derivatives

2-aminopyrimidine, concluded that

substituted guanidine is reacted with dicarbonyl compound (1).

Using the known reaction, new 8 / J-nHpHNWjuiHoaminomethyl-10a-zrgoline derivatives of the general formula 1 can be obtained. The purpose of the invention is {and - to solve the range of biologically active ergoline derivatives.

This is achieved by the prevailing pososum.

for the preparation of 8/3-pyrimidipoamipomethyl-Yua-ergoline derivatives of the general formula I, namely that diadrolysargamine or Lmsgyl-dihydrolisergamine is subjected to an interaction with a compound capable of transforming

an amino group to a guaiidino group, and the corresponding 6-methyl-or 1,6-dimethyl-8/3-guanidanomethyl-10 o-ergoline thus obtained is reacted with a dicarbate compound of the general formula RiCOCHR.iCORj (I),

where RI.RZ and РЗ have vyscheuka-zai 1 () e -chuyuiye, at a temperature of 10--150 ° C and thus obtained derivative 8-rIiPi and; u oroamIlomethyl-10 a-ergol1I are cleared.

Claims (2)

As a compound, ciiocoujioio transform yarn of an amino group in uani / shno pyiniy, is selected presumably from the group consisting of cyanamide, l-guanyl-3. 3-deimerschirazole S-alkylisothiourea or O-alkyl isomers or their salts. Distinctive features of the method are the transformation of dihydrolisor or lme tyldihydrolizargamin into the corresponding derivative of 8E-guanidinometal-10y-ergodsh., Which is subjected to interaction with a p-asarbovlly compound. Derivatives of 8 | 3-g5. Anidomelyl 10a-ergolic are obtained in an organic solvent, presumably at the temperature of its boom. The reaction proceeds as follows: example. ib-dimethyl-8 | 3- (5.ltffltpo2pyrimidinomeminomethyl): 10 a-ergolin. I CTBOp 5 g of 1-methyldagydro isergha and 4 g of 1-guanyl-3,5-dimesh1Pyrazole nitrate in 200 ml of ethanol are heated with a refrigerator for 7 h. The solution is concentrated until the onset of crystallization, and 4 g of 1,6-dimethyl-8 nitrate; 3-guanidinomethyl-10 se-zrgol on, m.p. 242-244 ° C. To a solution of 3 g of the product in 120 ml of methanol was added 4.8 g of sodium salt of W1-ro malondialdehyde and 0.1 ml of piperidine, the mixture was displaced for 8 hours, yielding 2.5 g of 1.6 d. 8 (5-nitro-2-pyrimidinoaminomethyl) -10-№-ergoline, t. Pl. 204-206 ° C. Example 1 1,6-dimegsh1-8 / 3- (4,6-da: methyl 2-tshrimidinoaminomethyl) -10 a-ergolin. A solution of 4 g of Imethyldihydroplastic ffl in 150 ml of ethanol is heated under reflux for 4 hours with 2 equivalents of cyanamide, neutralized with nitric acid and concentrated to the onset of crystallization, 2 g of 1,6-dimethyl-8 guanidinomethyl-Yua-ergol nitrate}; on . m.p. 242-244 C. When adding the equivalent of sodium methoxide to the nitrate 1,6-dimethyl-8 | 3-guanidinomethyl 10 a-ergoline, the corresponding freedom of axis is obtained}. 0.9 g of 1,6-dimethyl-8 | 3-human indomethyl-lO-a of Erg D long B base is dissolved in 20 ml of aigtylacetone and the solution is heated for 8 hours. The residue is evaporated and chromatographed on oxides to give 6 g of 1,., 6-demegyl-8 E- (4,6-dimets-1-2-pyrimidine) 5MJJ Edmethyl) -10a-eproline, m.p. 129-131 ° C pp. M 3. 3. 1,6-dimetsh1-8 | 3- (4-methyl-b-phenyl-2-1 Srimidt oaminomethyl) -10 a-ergoline. 1 g of 1,6-dimethyl-8/3-guanidinol, ethyl-10 a-erg base and 5 g of benzoyl acetone are heated to 80 ° C for 65 hours, then the mixture of KOfraicra-piipyiox in vacuum, and the residue by chromatography on alumina, is obtained 0.5 g of 1,6-dg1methyl-8 (3- (4-methyl-6-phenyl-2-pyrimidinoap, scomomethyl) -10 sk-ergoline, mp 192-194 ° C. And p and m e p 4. 1,6-dimethyl-8 | 3- (5-chloro-2 pry lid1shominomethyl) -10 a-ergoline 2g 1, b-dimethyl-8 j3-hyancidine-10a-ergooJBl to the base of the base and 2 equivalents of chlorometal dialdehyde heated in butanol to 110 ° C for 4 h. Then the mixture is co-devolved in vacuum and the residue is chromatographed on alumina, 1.2 g of 1,6-dimethyl-8 jЗ- (5-chlorop-2-Shlpidinokinometsi I) -} Oo; -hergolina are obtained, mp 190-192 ° C. Example 5. 1, 6-dimethyl-8 jЗ- (5-nitpo2-pyvidd dinoamine w) -10 a-ergoline. Equivalent to methylmethydichdol of olysergamin is reacted with an equivalent of 3-ethyl isothiourea hydrochloride in an 80% ethanol at 50 ° C for 3 hours for 3 hours. 1, BD lmethyl-8 a-guanidinomethyl-10/5-ergoline is condensed with the sodium salt of nitromalondialdemide (1: 1) according to the procedure described in example 1. PRI me R 6. 1,6-dimethyl-8 iZ- ( 5-sh tpo-2pyrimid raoaminomethyl) - 10 a-ergolin. According to the procedure described in Example 5, but you have S-these isothioureas, 0-ethylisourea is used, and 1,6-dimethyl-8/5-guanidinomethyl-10 a-ergoline hydrochloride is obtained. Example. 1,6-dimethyl-8 (5-amino2-pyri, chshdinoamino-methyl) -10 a-ergoline. According to the method e, described in Example 1, 1,6-dimethyl-8 13- (5-amino. 2-pyrimidino-amino-negl) -10 a-ergoline, m.p. 176-178 ° C. 0 e rme 8. 8. 6-methyl-8 (3- (5-nitro-2-1harimddino-shnomet -sh) -10 a-ergoline. A solution of dihydrolysergamin and nitrate 1 .guanml-3,5-d; methylpyrazole in ethanol, heating under reflux for 7 hours At crystallization of the reaction mixture, 6-methyl-8/3-guanidinomethyl-10 a-ergoline nitrate is obtained, mp 235-237 ° C. The product is reacted with nitromalindialdehyde according to the procedure described in example 1 , 6-methyl-8 / 3- (5nitpo-2-sh pimidinoaminomethyl) -10 a-ergoline is obtained. According to procedure I described in example i, the following compounds are obtained: 1,6-dimethyl-8 j3- (2-pyrimidino aminomegly) - Yua rgolin, 1,6-dimel-IL-8 / J- (5-phenyl-2-pyrimidinoamino1Sh1) ilO-ra-ertolin, 1,6-dimethyl-8 i8- (5-dimethylamino-2-m simidino-minomethyl) -10 a- ergoline, 1,6-dimethyl-8 (5-vcegylamino-2-pyrimidinoaminomethyl) 10 a-ergolin, 1,6-dimetal-8 | 3- (5-acetylamino-2-pyrimidinoaminomethyl) -10 a-ergoline, 1, 6-dimethyl-8 / 3- (5-methoxy-2-pyrimidino aminomersh1). 10-a-ergoline, 1,6-dimethyl-8 | 3- (5-cyano-2-pyrimidanoaminomethyl) -10 a-ergoline. Claim 1. Invention method for production of Schrmidinoaminomethyl-10 a-ergolic formula N-4 1CH3 where R is hydrogen cll methyl, RJ and R 5 is hydrogen, hydrogen or phenyl, RS hydrogen, halogen, methoxn, phenyl, nigro, asrBfflo - Or shi anogrutm, characterized in that d.h. ilggg. 6-yes. mep1P1-8 jS-ryaio iHOMenifi-10 a-zrgo.shpg is subjected to interaction with D gkarbogo1l with the formula of RtCOCHRjCORj (I) where H1, H-2, Vz have the above value, bought 10-150 C and thus obtained 10 (3–11 irim | di amylpomethyl-10 a-argosh- and isolated. 2. The method according to p. I, that is, that is able to transform ap iHorpyimy to grtile 1cogra (y, choose from rpyrsubs, consisting of: i, N.iiuMnm, i-fyaшO1 -3, 5-dmmglnl nrazola, S-alkylization; lu) isky or O-alkshzomochechevik ujii kkh salts. Information sources. | ti1 tys in addition at examination: I. IbrspoUiiKJHi4scKise of the compound of ed. R. Elderfidz, M., 1Ш, i960., Vol. 6, p. 200.