SU1192614A3 - Method of producing 6-hydrazino-pyrido-(2,1-b)-quinozalin-11-on derivatives or salts thereof - Google Patents

Abstract

Compounds of the general formula <IMAGE> (wherein R, R<1> and R<2>, which may be the same or different, each represents a hydrogen or halogen atom or a nitro, carboxy, cyano, C1-4 alkoxy, C1-4 alkyl, amino, or hydroxy group or an alkoxycarbonyl group in which the alkoxy contains 1 to 4 carbon atoms; or R and R<1> together represent a methylenedioxy group, and R<2> represents a hydrogen atom; R<3> represents a hydrogen atom or a C1-4 alkyl group; R<4> represents a hydrogen atom or a C1-4 alkyl group, a naphthyl or pyridyl group or a phenyl group substituted by 1 to 3 substituents, which may be the same or different, selected from halogen, C1-4 alkyl, C1-4 alkoxy, phenoxy, hydroxy, nitro, amino, cyano, carboxy, alkoxycarbonyl in which the alkoxy moiety contains 1 to 4 carbon atoms, alkanoyl in which the alkyl moiety contains 1 to 4 carbon atoms, methylenedioxy, trifluoromethyl, phenyl and mono- or di-alkylamino in which the alkyl moiety contains 1 to 4 carbon atoms; and each dotted line represents an optional further bond and the salts, optical and geometrical isomers and tautomers thereof are intermediates in the preparation of Rutaecarpine and the analogues thereof. The compounds of formula I may be prepared by reaction of a pyrido[2,1-b]quinazolin-11-one with a diazonium salt or with hydrazine or a derivative thereof.

Description

one

This invention relates to a process for the preparation of new derivatives of 6-hydrazino-pyrido (2,1-b) quinazoline-11one of the general formula

nitro, carboxyl, nitrile, C C - alkoxy, C-C4 alkoxycarbanyl, C4-C (ralkyl, amino group or hydroxy group,

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diluted with glacial acetic acid and then a solution of 2.0 g (o, 01 mol) 11-oxo 6,7,8,9-tetrahydro-1 H-pyrido (2, 1-b) quinazolium-e 10 ml of 50% acetic acid. The reaction mixture was stirred at (5) 0 C for 3 hours and then left in the refrigerator overnight. The precipitated crystals are filtered and washed with water. Received

10 6-phenylhydrazono-11-oxo-6,7,8,9-tetrahydro-11H-pyrido- (2,1-b) -quinazolines, if necessary, instantaneously recrystallize from n-propa-iol.

15

The compounds obtained are listed in Table. one.

and R together methylenedioxy R c

group;

R is hydrogen; g-

R4 is hydrogen or C (, C 1 -alkyl, known conditions one or three times, equally or differently substituted by halogen, C 4 -C 4 -alkyl, C-C-alkoxy, phenyloxy, hydroxyl, nitro, amino, cyano, carboxyl, C / j-C-alkoxy-carbonyl, C 5 -C4-alkanoyl, methylenedioxy, trifluoromethyl, phenyl, C-C -dalkylamino, phenyl, naphthyl or pyridyl,

the dotted line, under certain conditions, is a C-C bond from a friend,

or their salts, which can be used as starting materials in the preparation of alkaloids.

The purpose of the invention is the synthesis of new compounds that are the starting material for the preparation of alkaloids.

The reaction is carried out at (j-O C in a mixture of water with an organic solvent or in an organic solvent miscible with water.

Alkane carboxylic acids can be used as the inert organic solvent.

Examples 1-22

To a mixture of 0.01 mol of aniline derivative and 5 ml of 1: diluted 28% aqueous hydrochloric acid slowly, at -5 ° C and with stirring and cooling, 0.69 g, (0.01 mol) of sodium nitrate in 5 ml of water. The reaction mixture was stirred at (-5) for 0.5 h, after which the pH of the reaction mixture was adjusted by adding sodium acetate to 4. The reaction mixture

Examples 23 and 24. The process is carried out similarly to examples 1-22, however, instead of 11-oxo-6,7,8,9-tetrahydro-11H-pyrido- (2,1-b) -quinazoline use 11-oxo-1,2 , 3,4,6,7,8-octa-hydro-1 1 H-pyrido (2, 1-b) -quinazoline.

The compounds obtained are presented in Table. one,

 ., Examples 25-28. The process is carried out analogously to examples 1-22, however, 2,3,4-trimethoxy-11-oxo-6, 7,8,9-tetrahydro-11H-pyrido {2,1-b ) -quinazoline, in example 26, 11-oxo-6,7,8,9-tetrahydro-11H-pyrido- (2,1 -b) -quinazoline-2-carboxylic acid, in example 27 methyl-1- oxo-6,7,8,9-tetrahydro-11H-pyrido- (2,1-b) -quinazo-LIN-2-carboxylate; in example 28, 1I-oxo-6,7,8,9-tetrahydro- 11H-pyrido- {2,1-b) quinazoline,

The resulting 6-phenylhydrazono-1 1-oxo-6,7,8,9-tetrahydro-11H-pyrido {2,1-b) -quinazoline derivatives are listed in the table below. one.

Products may be recrystallized from n-propanol.

Example 29. 0.93 g (0.01 mol) of aniline is dissolved in 5 ml of 1: 1 diluted 38% aqueous hydrochloric acid at -5 ° C, then 0.69 g (0) is added dropwise with constant displacement and cooling. , 01 mmol) of sodium nitrate in 5 ml of water. The reaction mixture is stirred for 0.5 hours at -5 ° C, after which the pH is adjusted to 4 by addition of sodium acetate and the mixture is diluted with 10 ml of acetic acid.

3

lots. A solution of 2.28 g (0.01 mol) of 6-h1) Ormyl-1 1 -oxo-b, 7.8, E-tetr agidro 1H-pyrido- (2 ,) - quinazoline in 30 MP of acetic acid. The reaction mixture is stirred for i h and then left overnight in a refrigerator. The precipitated crystals are filtered and washed with water. 3.1 g (91% of b-phenylhydrazono-6,7,8,9-tetrahydro-11-co-11H-pyrido- (2,) - tsinazolinghydr, chloride, mp 255 ° C are obtained.

Calculated,%: C 63.60; H 5.04; N 16.48; C1 0.16.

c, gH N4001

Found,%: C 63.44; H 4.98; N 16.59; C1 10.11.

Examples 30-40. The process is carried out analogously to examples 23 and 24, using as starting materials derivatives of H-oxo-1, 2,3,4- 6,7,8-octahydro-11H-pyrido- (2,1-in) hnnazoline.

Derived 6-phenylhydrazio-11-yuco-1,2,3,4,6,7,8-octahydro-I1H-pyrido- (2,1-b) -quinazoline

The crystals separated out after diazo-bonding are suspended in 5% sodium hydroxide solution, after which the aqueous solution is shaken with chloroform. The chloroform solution dried over sodium sulfate is evaporated and the residue is crystallized.

Example 41.O., 46 g (0.005 mol) of aniline is dissolved in 3 ml of I: 1 diluted 38% hydrochloric acid at -5 s, after which

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under constant stirring and cooling, 0.35 g (0.005 mol) of sodium nitrite is added in 3 ml of water. The reaction mixture was taken up at (-5) for 0.5 h, after which the pH was adjusted to 4 by addition of sodium acetate. A solution of 6-formyl-11-OXO-1,2,3,4,6,7,8-octa-10 hydro-15 H-pyrido- (2,1-b) -quinazoline in 15 ml of 75% - is slowly added dropwise to the mixture. acetic acid. The reaction mixture is stirred at a temperature below for 3 hours, then left overnight in cold water and diluted with 30 ml of water. The crustaceans that are left are filtered and rinsed with water. 1.3 g (73%) of 6-phenylhydrazio-11-oxo-1,2,3,4,6, 8-okta hydro-I H-pyrido- (2., 1-b) -hina-20 are obtained. zoling hydrochloride with. m.p. 242-244 C.

&Amp; N,%: C 63.59; H N 15.61; From 9.88.

Found,%: C 63.21; H 6.28; 25 N 5.75; From 9.65.

Compounds of general formula (I) are used to produce new up-pockets — analogues of rucapprin of general formula for a chopper.

The diuretic effect of new alkaloids and the well-known rutecarpine is shown in Table. 2

From the data it follows that obtained from the pr, the subject proI

interstitial compounds alkaloids have a significantly stronger diuretic effect compared with rutecarpine.

table 2

Female

New alkaloid.

Male

Methylcel-

Same 5 lozolv

Rutecarpine

13.56

. 10.05 14.17 10.42

3.8

5.05 4.35 6.08 4.75 7.15 4.80 7.10

Claims (1)

The method of obtaining derivatives of 6-hydrazino-pyrido- (2,1-b) -quinazoline-11-one of the general formula is differently substituted with halogen, C <—C4 — alkyl, C (—C4 — alkoxyl, phenyl-silo, hydroxyl, nitro, an amino group, a cyano group, a carboxyl, C4 — C4 — alkoxycarbonyl, C ₍ —C ₄ -alkanoyl, methylenedioxy, trifluoromethyl, phenyl, C ₄ —C ^ - dialkylamino group phenyl, naphthyl or pyridyl; dashed line — under certain conditions, there is another C — C bond, or salts thereof, distinguished by the fact that the compounds of the general formula where R _f , R ₂ , R ₃ , R ₄ and the dashed line have the indicated meanings; R ₆ is hydrogen, formyl formulas or a group N where Rj, R ₂ and R ₃ are the same or different and mean hydrogen, halogen, nitro group, carboxyl, nitrile, C | -C4 alkoxy, C {-C4 alkoxycarbonyl, C ^ -C ^ -alkyl, amino or a hydroxy group, or R and R ₂ are together methylene dioxy; R ₃ is hydrogen; R ^ - hydrogen or Cj-C ^ -alkyl ;, R ₅ - under certain conditions, one to three times, the same or where - C, -C ₄ -alkyl, is reacted with a diazonium salt of the general formula Θ Θ R5-N2CI where has the indicated meanings, with the exception of the hydrogen atom and the C ^ -C ^ -alkyl group, with the isolation of the target product in free form or in the form of a salt. 09) SU mi 1192614