DD206996A1 - PROCESS FOR PREPARING SUBSTITUTED 9H-9-OXO-S-TRIAZOLO (5,1-B) CHINAZOLINES - Google Patents

Abstract

The invention relates to a process for the preparation of novel heterocycles of the formula I. The 9H-9-oxo-s-triazolo (5,1-b) quinazolines of the formula I obtained according to the invention, in which R below 1 = aryl, substituted aryl R below 2 = H, alkyl, substituted alkyl, aryl, substituted aryl R below 3 = H, signify halogen, are obtained by reacting 2,3-diamino-3,4-dihydroquinazolin-4-ones with saeder derivatives. The novel compounds I have antihistaminic, antirheumatic, diuretic or antihypertensive properties. Field of application is the pharmaceutical industry.

Description

A process for the preparation of substituted 9B-9-OSO-s-triazolo (5,1-b) -iazaazolines

The invention relates to a Terfahrem for the preparation of otop substituted 9H-9-oxo-s-triazolo (5> 1-b) ohinazolinen the general formula I,

in the Е ^ жАгуі, substituted aryl

E ₂ = H, allyl, substituted alkyl, aryl, substituted aryl

E, = E, signify halogen.

Among these triazoloquinazolinones are compounds which have aatiacapb.ylactic, anti-viral, diuretic or antihypertensive properties. The invention is applicable in the pharmaceutical industry ac.

Characteristic of the technical LSs ^^ pt ^ Ti

It is known that I-diamino heterocycles react with different reagents by the attachment of a 1,2,4-eriazole ring (Bouben-Weyl, Methoden der organischen Chemie, B, 2/2, Qeorggieme Terlag, Stuttgart 1967; а.-гатаі, She Chemistry of amidines and imldates, KM Watson and DeHeilson.John Wiley & - Sons; 1975ϊ Bonden, Hew Tork, Sydney, Toronto). Such agents are substituted or substituted carboxylic acids and carboxylic acid derivatives, such as esters, dicarboxylic acid esters, halocarbonates, phosgene, thiophages, cyanate esters, isocyanates, isothiocyanates, urea, CS ₂ and SSureennydride (Houben-Weyl, loo.cit.j BD-Ιΐ 139 715i E Zottl £ e and H. Kunuistedt-Pharmacia 21 f9, 124, 12, 462, 507 (1978); £, 800 (1980). Extensive literature on the preparation of triazoloquinazolines, etc. (Sriazoloquinazolinones and their pharmacological effects are in the patents DD-KP T3S 715 and WP 0OT D 229 905 / O-containing (yergl., lalukdax, fB, Sengupta, SE and AK Daxta, India I »Ohem 19 B, 638 (Ί980) · About the meaning топ Ohimazeliaioii-DeriTaten in 4-Arzneimittelforscflung is reported in the literature wordea (S. Johne, Pharmacy 36. 583 (1981). upper presentation and pharmakologisene effect топ substituted 9H-9-oxo-striazelo _(5> 1-b) ohinazolinea nothing is known yet.

Object of the invention

Bs is the object of the invention to provide novel, biologically active heterocycles which act as antihypertensives, antibiotic agents and as platelet aggregation inhibitors.

Explanation of the essence of the invention

The invention is based on the object of developing a process for the preparation of substituted 9H-9-oso-s-triazolo (5,1-b) eninazolines. The task was solved so that. S, 3-diamino-3,4-dinydroohinazolin-4-ones of formula IX,

II NH-R ₁

in the .Д- = Агу1, substituted aryl S ^ = H, halogen

mean, with possibly activated acid derivatives !! of formula III,

III

in which

7 alkyl, ^И 2 О; HalOjäe alkyl, os alkyl, Halog ^ CH, aryl of alkyl, Qs. aryl

OEi n = 0 to 3

^G n ^H 2n + 1 ^0CB; Halogen;

Acetic anhydride OOC-OH-; Aldehydes H; Isothiocyanates (2, R ₂ J = S; isocyanates (X ₁ EgJ = QJ mean, under oxidative Oyelisierung

Melted or in organic solvent)

preferably under reflux conditions, are reacted:

The invention will be explained in more detail by means of exemplary embodiments.

Icelandic games (cf. table),

(n-0 to 3) zn IH ₂ = alkyl

A given amount II is refluxed with formic acid, eic acid or propionic acid under reflux for 3 hours. Thereafter, the reaction batch is added to Biswas в er and sucked the precipitated substance.

2. Reaction of II with ^a ^ 2n-k% ^GCS - ^{to τ} Bg ^ AUcylfBUbetitu-

iertea alkyl

0.01 mole of II-is reacted with 0.01 mole of acid halide in 20 ml of the corresponding alkanoic acid (e.g., propionyl chloride in propionic acid) under reflux for 3 hours. Work-up as under T.

3. reaction of II with acetic anhydride to II E ₂ = CH,

A given amount of II is slightly overlooked with acetic anhydride and heated in a water bath for 5 hours. To the. Methanol is added to the reaction mixture, the resulting ethyl acetate is evaporated and the substance is washed with water.

4. Reaction of the hydrazones of II with lead tetraacetate

to 1, IlI

0, Qt mol hydrazone is dissolved in anhydrous acetic acid and treated with 0.015 Hol lead tetraacetate. Upon cooling, the compounds I, aryl crystallize out.

Reaction of II isit isothiocyanates or isocyanates to Semi tb-iocarbagid- ¹¹ ^ d semicarbazide derivatives

a) Equimolecular amounts II and isothiooyanate are reacted in ethanol 1 Ь under reflux.

b) Equilibrium Jralars! tight II and isocyanate are reacted in benzene 1 Ii under reflux. The substances fail.

HC ₆ H ₄ -

Yield 67 %; Thrust, - 264-268 (n-butanol) j

Hr. 13,23 gef. H 12,96; C ₂₁ H ^ ₅ Bt ₂ S ₅ O ₂ . (529.2)

0 o

SNH-C-NH - «<- C ₁₀ ^H

N H - Q, H ₄ - P - ß i-

Yield 85SSj Schmb. 214-219 (n-butaiol) i

.Ber. 12.09 Hgef. 12.33; O ₂₅ H ₁ ^ r ₂ H ₅ O ₂ (.579,3)

Table: 9H-9-oxo-s-triazolo (5,1-l>) ohiaazoline I

^E 1 ^H 2 E ₃ Yield ft Melting range ( ⁰ C, n-butanol) Bulk formula Molar mass If t, over / gef P-Ol-C ₆ H ₄ H H 95 292-294 C ₁₅ H ₉ Ci B ₄ O 296.6 18,88 19,16 P-Cl-O ₆ H ₄ GH ₃ H 98 268-271 ° 16 ^H 11 ^C1 V 310.6 18.02 17.72

P-Br-C ₆ H ₄ I CH ₃ 7-Br J 74

222-227

420.0

188-193

434.1

13:33 13:16

12,91 13,02

location 1 η .-01-C ₆ H ₄ Table H ₂ E ₃ 7-Br Yield % Sohmelzbereioh (° 0, n-Bu-tanol) Molecular Formula Molar mass IT % over / under a) n-butanol b) glacial acetic acid H 91 242-247 (a) O ₁₄ H ₈ BrClN ₄ O 363.6 15,50 15,72 P-Ol-O ₆ H ₄ OH ₃ 74 250-256 (a) 389.6 14.38 14.55 O ₂ H ₅ 61 221-227 (Ъ) O ₁₇ H ₁₂ BrOur ₄ O 403.7 13,88 14,45 - ^C 4 ^H 9 76 170-175 (b) O ₁₉ H ₁₆ BrOIiT ₄ O 431.7 12,98 13,15 H 90 224-226 (a) O ₁₅ H ₈ BrOlM ₄ O 375.6 0 47.96 H 2,15 47,80 2,60 H 14,92 15,27

Claims (1)

1. Process for the preparation of substituted 9H-9-03EO-s-triazoloC5> 1-b) quinazolines of the I-formula I, ia the R ₁ = aryl, substituted aryl E ₂ = H, alkyl, substituted allcyl.aryl, substituted aryl E, = H. halogen characterized in that 2,3-Diarai.no-3,4-dihydegoquinazolin-4-ones of Pormel II, ! -NH ₁ NH-R ₁ II in the E ₁ = aryl, substituted aryl £, = - H.Halogen
mean, with acid derivatives !! the IOrmel III, III in the Σ, y, E ₂ mean, be implemented. Z. Procedure пвсЬ Punkt t characterized in that the reaction топ compounds of formula II with compounds of formula III- under the conditions of oxidative cyclization, under melting conditions or in organic Laaungami-t-teln., Уогаавачіеіаа under
is made.