SU461621A1 - Method for producing substituted 4-amino-2-styrylquinazolines - Google Patents

Description

The reaction is usually carried out at 12O-2OO, preferably at 145-150 ° C. The process can be carried out in the presence of a basic or acidic catalyst, for example, acetic anhydride or piperidine. The starting compounds are prepared in a known manner. Example 1. A mixture of 2 g (7 2 metip 4- (d-diethylamino-t-methylbutylamino) x nazoline, 2.6 g (18 mmol) f-chlorobenzaldehyde, and: 8 ml acetic anhydride is heated with stirring at 145-15 ° C for 10 hours with chromatographic control of the reaction.The reaction mass is treated with 5O ml of 3% hydrochloric acid, boiled with charcoal, filtered, basified with 25% aqueous ammonia solution and extracted ether The ether solution is dried with magnesium sulfate, evaporated. The residue is dissolved in alcohol while heating is added Phosphoric acid solution to pH 4 is added. The precipitate of HeckoribJicpl® diphosphate is rubbed with then with acetone, filtered and dried to constant weight in a drying cabinet at 80 ° C Diphosphate yield 2- (4 - chlorostyryl) -4 (- diztilamino-methylbutylamino) hdnopina 2.42 g (56,, 3%). FoundGo: R 10.30; N 8.68. Calculated,%: P 1O, 01; N9.05. Dipicrate: mp. 219 -220.5 C (from elletsna.) Found,%: C 50.53; P 4.40; M15.7YA C | 4.09. - 4 C- S 33 ° 7 Calculated,%: C 50.43; H 4.24; N 15.89; Cr 4.03. : P P m ime R 2. A mixture of 3.1 g (12 mm, 2-methyl-4-diethylamino-7-chloroquinazoline, 2.41 g (14 mmol) of y-chlorobenzal deipa and 12 ml of acetic anhydride is heated for 3 hours at 148-150 ° C. The reaction mass is poured into 90 ml of 3% hydrochloric acid heated to 90 ° C. After cooling, the acidic solution is extracted with ether to remove fv-chlorobenzaldehyde. Then the aqueous solution is alkalinized with ammonia and the ether is extracted. evaporated, the residue (3.18 g), according to the data of chromatography on a plate with alumina 2- (4-x "r1Orstiryl) -4 -diethylamino-7-chloroquinazo-LING mixed with the starting 2-methyl-4-diethylamino-7-chloroquinazoline is divided into

, rolled out of absolute alcohol. 3.48 g (52%) of 2- (4-chlorostyryl) -4 (N-piperidino) -7-chloroquinazoline are obtained, m.p.

, 148-149 ° C. Light yellow crystals 60 soluble in ether, acetone, benzene, ascending alumina chromatography column, eluted with benzene. 1.35 g (30%) of pure 2 .. (4-chloroxyryl) -4-diethylamino-7-chloroquinazoline are obtained, m.p. 118-119 ° С (from heptane). Found,%: C 64.44; H 5.08; N 11, OP Q Vykskspeno. C, 64.52; H5, i4; N11.29 and 1.83 Gsmesi 2- (4-chlorostyryl) -4-diethylamino-7-chloroquinazoline and 2-methyl-4-diethylamino-7-chloroquinazoline. Example 3. A mixture of 4.1 g (14.9 mmol) of 2-methyl-4-phenylamino-7-chloroquinazoline, 3.5 g (23 mmol) of P-nitrobenzaldehyde,. 1.25 g (15 mmol) of anhydrous sodium acetate and 20 ml of acetic anhydride are heated with stirring and at a temperature of 150-152 ° C for 5 hours: “When the reaction mass is cooled to 80–85 ° C, a precipitate is formed, which is filtered, washed with acetic acid anhydride and treated with 6% hydrochloric acid solution, heated to 8O-85 C. The precipitate is filtered, washed with water, transferred to a base, which is recrystallized from ethyl acetate. Obtain 2.6 g (42%) 2- (4 nitrostyryl ) -4-phenylamino-7-chlorquinazoline, so pl. 242-243 / C. Crystalline (yellow substance is soluble in chloroform, worse - in alcohols, ethyl acetate, insoluble in ether and water. Found: C 65.45; H 4, O2; N13.68. S2. Calculated,%: C 65, 59; H 3.75; N13.91. P R m e R 4. A mixture of 5 g (19.1 mmol) of 2-methyl-4- (N-piperidino) -7-chloroquinazoline, 4.02 g (28 , 6 mmol) P-chlorobenzaldehyde, 1.64 g (20 mmol) of anhydrous sodium acetate and 2O ml of acetic anhydride are heated with stirring and 150-152 seconds for 5 hours. 135 ml are added to the reaction mass, cooled to 85 ° C. 8% hydrochloric acid heated to -85 ° C. After cooling, the The precipitates were filtered off by filtration, washed with ether (weight 6.03 g), dissolved in water, alkalinized with a 2O% solution of potash and extracted with ether. The ether extract was dried with potash and evaporated. The residue (4.4 g) was recrystallized from chloroform, ethyl acetate, worse — in alcohol j Findayo,%: C 65.5O; H5, O1; Ct 18.43; I N10.69. Sl l9 2S Calculated,%: C 65.63; H 4.98; Ci 18.45; N 10.94. I Guide; Chloride, m.p. 271-272 ° C. igemeICTBO is soluble in ethyl alcohol, 1methyl | alcohol, worse - in chloroform, ada - tone, water, insoluble in ethyl acetate, benzene. Found,%: P. {25,19; N9.89. :; Script,%: Ct 25,28; M 9.99; PRI me R 5. A mixture of 4.82 g (14.9 mmol) of 2-methyl-4-diethylamino-7-chloro J ,. . ,,. ... | quinaz6lin, 4.4 g (29 mmol) p -nitro benzaldehyde, 1.72 g (22 mmol) of anhydrous sodium acetate and 20 ml of acetic anhydride are heated with stirring and 150-152 ° C for 5 hour. IK of the reaction mass, cooled to 85 ° C, is added 65 ml of a 6% solution of hydrochloric acid heated to 80-85. The precipitated precipitate is filtered, washed with water and ether, transferred to a separatory funnel, 70 ml of 1O are added. % potassium solution and extracted with ether. The ethereal extract is dried with potash, evaporated. The residue (6.7 g) is recrystallized from 400 ml of absolute alcohol. The crystals are filtered off, get 4,1; (55%) 2 - (4-nitrostyryl) -4-diethyl but-7-chloroquinazoline, so pl. 160-161 ° C. It is soluble in acetone, benzene. : chloroform, worse in the ether insoluble in heptane and water, Foundo,%: C 62.9O; H 5, On; Ct 9.3 N14.43. i So l9 402: Calculated,%: C 62.74; H 5.00; C1 9.26; N 14.64. eHydrochloride, so pl. 267-268 C (decomp.). It is soluble in ethyl alcohol, chloroform. worse - in methyl alcohol, acetone, insoluble in ether, ethyl acetate, benzene and water. Found,%: Ct 16,53; N 13.12. o 0 19 "LVL calculated.%; SS 16.91; Nl3.36. EXAMPLE 6 A mixture of 5 g (16.7 mmol 2-methyl. -4- (b-diethylamino-methyl butyl amino) quinazoline, 7, OZ g (50 mmol) o-chlorobenzaldehyde, 2. O7 g (25, 2 mmol of anhydrous sodium acetate and ZO. Ml of acetic anhydride is heated with stirring and 15O-155 C for 6 hours. The reaction mass is filtered; the solution is withdrawn and poured into 10O ml of 10% hydrochloric acid heated to. | The hydrochloric acid solution is filtered, the extract is extracted with ether of an impurity of a minor nature, the solution is alkalinized and extracted with chloroform. The chloroform extract is dried with potash, evaporated. The residue (4.6 g) is solution t in ether and acidified with hydrochloric acid alcohol solution. After two recrystallizations of the precipitated isopropanol, 3.45 g of 1 (42%) dihydrochloride 2 -. (2-chlorostyryl) 1-4- {d-diethylamino-ct - methylbutyls 1) quinazoline with a melting point of 240-241 C. A crystalline substance, well soluble in water, worse - in alcohols, insoluble in afer, acetone, benzene. Found: Cf 21.44: W 11.30. Calculated,%: Ct 21.45; N 11.45. PRI me R 7. A mixture of 1 g (2.98 mmol): 2-methyl-4- (5 X diztilamino - methylbutylamino) -7-chlorochinazoline, | 1.38 g (9.1 mmol) vanillin and 10 Piperidine drops are heated with stirring and 125-130 C for 4 hours. The reaction mixture was triturated with dry ether. The precipitate formed was filtered off and converted into phosphate, which was recrystallized from methanol. 1: O5 g (53%) of diphosphate is obtained - 2 (3-me.; Toxi-4-oxystiryl) -4- (3-d-ethylamino; C-methylbutylamino) -7-chloroquinazoline. m.p. 239-24 ° C. The yellow crystalline substance is soluble in water, worse in alcohols, insoluble in chloroform, ether, acetone. Found,%: C 46.75; H 6, O2; Ct 5.21; N 8.8О; R 9.34. N 4 ° 2-2 zR 4 Calculated,%: C 46.95; H 5.91; et 5.33; N8.43; R 9.32. Similarly, 2- (4-chloro-styryl) -4- (S-diethylamino-d-methylbutylamino) -7-chloroquinazoline can be obtained. 2- (4 nitrostyryl) -4 - ((S-diethylamino-c. -Methyl-butylamino) -6-methoxy-quinazoline. 2- (4-nitrostyryl) -4- (Y-piperidino) -6-methyl-quinazoline, 2- (4- nitrostyryl) -4- (piperidino) -7-chloroquinazoline. 2- (3-chlorostyryl) -4-diethylamino-7-chloroquinazoline and other similar compounds with yields of 42-65%.

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Subject invention

1. A process for the preparation of substituted 4-amino-2-styrylquinazolines of formula I

where R is hydrogen, halogen, lower alkoxyl, lower alkyl; i R is hydrogen, lower alkyl;

R -) "from alkyl, phenyl, dialkyl but noalkyl;

moreover, and and R, together with the nitrogen atom, mean piperidine, R, R i R simultaneously mean hydrogen, halo, nitroxy or lower alkokoi-group or their salts, from that, (;

that 2-methyl-4-nminoh: inazoli general

formulas I

NRR

Claims (3)

12 10 where R, R and R have the above values are interacting with correspondingly substituted aromatic aldehyde when heated. ; 2. The method according to paragraphs. 1 and 2, differing from the fact that the reaction can be carried out in the presence of a basic or acidic catalyst, for example, acetic anhydride or piperidine. 3. The method according to claim 1, wherein the reaction is carried out at 120-200 ° C.