SI8311767A8 - Process for obtaining new pyridine compounds - Google Patents

Description

AMERICAN CYANAMID COMPANY

PROCEDURE FOR OBTAINING NEW PYRIDINE

Technical field

The present invention relates to the field of organic chemistry and relates to a process for the preparation of novel pyridine ......... compounds.

More specifically, the present invention relates to a process for the preparation of novel 2- (2-imidazolin-2-yl) pyridine and quinoline compounds. According to the ICP, this application is labeled:

Technical problem

This invention solves the problem of obtaining novel pyridine compounds that are useful for controlling undesirable plant species.

The state of the art

M »'' * *

The present invention provides novel compounds, so the applicant is not aware of the relevant methods for preparing them.

- -2--3Description of a solution to a technical problem for the preparation of pyridine

formulas:

The present invention encompasses a process

in which Λ represents COOR ^ and R _Q is hydrogen, alkyl may be substituted by C 1 -C 4 alkoxy, hydroxy, phenyl, furyl, halogenphenyl, C 1 -C 4 alkylphenyl, methoxyphenyl, nitrophenyl, carroxy, C 4 - C ^ alkckarbonil, or CC trialkilarnonijum grupom, C ^ -C ^ ,, alker.il PA1 and godno substituted with C ^ -C ^ alkoxy, phenyl, halogen or C ^ C ^ alcohols) κsikarbonil grupom, C _o -C cycloalkyl suitably substituted with one or 2 methyl groups, C 1 -C 6 / alkynyl substituted with one or two methyl groups or a cation selected from the group consisting of alkali metals such as K and Na, alkaline earths such as Ca, ammonium and organic ammonium; R is alkyl, R4 is C1-C4 alkyl or cyclopropyl and when taken together can be C1-C4 cycloalkyl optionally substituted by methyl, X is hydrogen, halogen, hydroxy or methyl, W is 0, Y and Z individually represent members selected from the group consisting of hydrogen, halogen, * methoxy, methylamine, or when taken together by LMQR

"Q and R ^ individually represent members selected from the groups s / containing hydrogen, halogen, methyl, provided that only one of L, M, Q and R _? may be substituent \ ent different .. from hydrogen, halo-4-5gens and methyl groups, the novelty of this process is in the friction that the compound of the formula

or the mixture PCI cyclizes with the aid of PCl ^ T ^ OCt * · / in toluene, at room temperature to 80 ° C, whereby this compound can be formed in situ.

»

2- (2-imidazolin-2-yl) quin: oline compounds are illustrated by the formula "(II):

«· In which au Rp Rg, W, B, A, I *» M, Q and R? defined previously with respect to formula (I) ·

Formula (II) 2- (2-imidazolin-2-yl) quinoline compounds which are preferred herbicides! an agent is one in which R1 represents methyl; R8 represents methyl, ethyl, isopropyl or cyclopropyl;

W is oxygen; B is hydrogen, CO-alkyl of C 1-6 alkyl, CO-phonyl optionally substituted by a chlorine, nitro or methoxy group; A is COORj, OHgOH or OHO; R 1 is previously defined in formula (X);

X is hydrogen 1 L, M, Q and R? each room selected from the group consisting of hydrogen, halogen, methoxy, nitro, alkyl of

CF ^, ON, N (C9j) ₂ , ^ 2 · ^SCH 5 BO2 ^OH 3 ^{p0 <and by the condition dQ ewm0} one Member of L, M, Q or R? may be nitro, CF ^, ON, N (GH ^) 2, NH ₂ , SCHj or S0 ₂ CHj.

A more preferred group of 2- (2-imldazolin-2-yl) quinoline compounds of formula (11) is one in which X, L and R are? hydrogen; R1 is methyl; R ₂ is methyl, ethyl, isopropyl or cyclopropyl; B is hydrogen or COCH1j A jo OOORj, OHgOH or CHO, and R4 is as previously defined in formula (I); W is oxygen and M and Q are each represented by a member selected from hydrogen, halogen, methyl, methoxy, nitro, OFj, CN, »(CH ₅ ) ₂ , NHg, SCH ^ or SOgOH ^, provided that only one of the members of M or Q may be a substituent other than hydrogen, halogen, motil or methoxy.

A more preferred group of 2- (2-imidazolin-2-yl) quinoline of formula (II) is that in which R is methyl; Rg is isopropyl; tf jo oxygen;

B, X, L, M, Q and R? are hydrogen; A jo COOR ^ where jo is R ^ alkyl of ^C 1 ^C 8 'hydrogen, ^C 1 ^-C 6 alkenyl, allcinyl of C 1 -C 8, ocycloalkyl of O 2 -Og or a cation selected from the group of alkali metals, alkaline earth metals, manganese, copper, - iron, zinc, cobalt, lead, silver, nickel, ammonium or aliphatic ammonium.

In the formulas 1, 1a and II shown above, alkali metals include: sodium, potassium and lithium, but still mainly m · ¹

-7-:

is also preferred the term organic ammonium ¹ 'defined as a group comprising a positively charged aa atom bonded aa to one to four aliphatic groups, each containing from one to 20 carbon atoms. Among the organic ammonium groups typical of the preparation of aliphatic ammonium salts of formulas (I) derived from imidazolinyl nicotinic quinols on the esters are the following: trialkynylammonium, monoalkanolammonium, dialcanolammonium, trialkanolammonium, cycloalkylammonium of O ^ -Οθ, piparidinium, morpholinium, pyrrolidinium, benzylammonium and their equivalent groups. Examples of halogens mentioned include chlorine, fluorine, bromine or iodine, but ou chlorine and bromine are preferred.

As previously shown, the present invention relates to

2- (2-imidazolin-2-yl) pyridine and 2- (2-imidazolin-2-yl) quinoline compounds and their application as herbicides, These novel pyridine and quinoline compounds are represented by formula (I) common to both groups compounds. Formula (II) is a specific self and refers to 2- (2-imidazolin-2-yl) quinolino.

Many of the step-by-step phases described herein and the topic are common to the preparation of the pyridine and quinoline derivatives of the present invention,

for the sake of convenience, the post-production stages limited to the production of quinoline derivatives will be discussed separately and followed by a discussion related to the production of pyridine derivatives.

Conveniently, about 2- (2-imidazolin-2-yl) pyridine ontr 'mulo (Ib) is obtained from dioxopyrrolpyridine acetomide and (IV), wherein Bp Bg, X, Ϊ and Z are previously defined by cyclization a strong bass such as 1,5-diazobiocyclo .0 undocane-5-β (DBU), in the presence of an inert erganic solvent such as xylo xol or toluene, obtains the eir d nu d zopyrrolpyridine formula at Sen. salt (III) · Keakoion mixture e · warms <v> temperatures between I00 ° 0 and 150 ° 0, and the genus ee removes from r '· ifion emesies during the reaction in convenient ways, such as using the Dean-Stark-ννβ water removal apparatus. J4 ¹ cinoj EMEA ee Tada add · jedan least equivalent c 'prikazanog formulom (V) K ^ OH, in kojoj B ^ is Cl gojočiji than hydrogen or a cation koji trimmed salt au,

X Ϊ i EU previously definieanl, and the thus obtained E "" nar va ee up to the presser foot refluktovanja partitioned between 100 ° C and 150 ° C _t to .la

2- (2-Imidazolin-2-yl) pyridine ester of formula (Ib). The Uknp action can be shown schematically as follows:

(IV)

- (III)

in which eu X, Y, Z, R.

and Rj are previously defined.

- within the framework of the process characterized by the preparation of 2- (2-iraidazolin-2-yl) pyridine ether of formula (Ib), cyclization of the carbamoyl nicotinic acid ester of formula (VI) is carried out with .to. for p ant * chloride at elevated temperatures. , generally between 60 ° C and 100 ° C. The reaction will conveniently be carried out in the presence of an inert organic solvent, such as Au or toluene or benzene. A good yields of the hydrochloric kyeline of the desired ester of formula (Ib) are obtained.

They are hydrochloric acid, the L _a where translations in ester of the formula (Ib), by dissolving the acid-addition salt »-obtained with an acid, in water and neutralizacijom so obtained solution of sa bazom, as well as ot o s sodium or potassium karbonftt. Overall reactions can be displayed in any of the following ways:

(VI)

X storm

-9 ·

in Roy A represents COOR ^ and R ^ is a substituent other than hydrogen or a salt-forming cation, and Rp X, Y, and Z »have the preceding equation · in a process characterized by the production of 2- (2- * jmidazolin-2 -yl) pyridine esters of the present invention of formula (Ib), cyclization of the turbanjoyl nicotinic acid ester was performed using a mixture of phosphorus pentulyl chloride and phosphorus oxychloride. The reaction mixture was stirred at room temperature for about 4 to 8 hours and then the POCl was removed in vacuo. The residual dcc> ae is treated with an organic solvent such as toluene. The solvent was removed and the residue treated with water and heated from 80 ° C to 100 ° C. After cooling, the pH of the aqueous mixture was adjusted to

5-6 using sodium bicarbonate, and the product is extracted with methylene chloride to give the desired product 2- (2-imidazolin2-yl) pyridine ester of formula (Ib). The reaction can be shown schematically as follows:

Y ·.

COOR,

R,

CONH-C-CONH r

R.

1 · PClc / POCl,

-? 2 - »

2. HgO (VI)

in which A represents COORj, 1 Rj is a substituent of the second moiety. of hydrogen or a cation that builds salts, and R ^, R ₂ , X, Y, and Z & a in the foregoing.

2- (2-imidazol-2-yl) pyridine esters of formula (Ib) in which A COORj and Rj represents alkyl of ° X- ° 12 · alkenyl of ^C 3 ' ^C 12' alkynyl of Oj-Ojo ' ^c cycloalkyl of Ο ^ -Οθ or a substituted derivative of these groups, and X, Y, Z, R ^ and R ^ are previously defined, may be converted to the corresponding amide where A represents CONH ₂ , by reaction with ammonia under ouperatmospheric pressure at temperature about 25 ° C to 125 ° C · This reaction takes place in a protic solvent such as phyto is lower alkanol or aprotic solvent such as tetrahydrofuran, dioxane and the like · Similarly, under iodine conditions, but substituting ammonia hydroxylaminor in this reaction; acid. These reactions can be schematically illustrated in the following ways

-12 (Ib)

CONHOH

Treatment of the thus obtained primary amide ea tltan-tetrachlo · rido and triethylamine, preferably in the presence of an inert aprotic solvent such as tetrahydrof uranium, gives the corresponding nit ryl. The reaction is mainly carried out in an atmosphere of inert gas, such as Slo is aaot, at a temperature between about 0 ° 0 and 10 ° C. The reaction of the knife to be shown schematically as follows:

in which X, 7, Z, R ^ and Rg have been previously described ·

The preparation of N-substituted llldasolinone derivatives of formula (VIII) in which B is COR ^ or SOgR ^ j A represents CH ^, ON or COOR ^ j W is Oj and R ^, Rg, R ^, X, T and Z have the foregoing meanings, except that Sto X and Z cannot be an alkylamino, hydroxy or lower hydroxyalkyl group, can be achieved by the reaction of a suitably substituted 2- (2-imidazolin-2-yl) pyridine of formula (I) with an excess of aoyl halide, acyl phthalide or sulfonyl-halc genide anger or in a solvent such as pyridine or toluene in «» «

-13 ~:

higher temperature between about 5θ ° θ to 125 ° C · The reaction can be shown schematically as follows:

R ^ COOl or (r ₄ co) ₂ o or

R ^ SOgCl

I i;

t>

in which A is CH ^, ON or COORjj Rj, «^ 2 * ^ 5 * ^ 4 * ^ 5 * have been predefined, eei» phyto Y and / or Z cannot be al kil— amino «hydroxy or lower hydroxyalkyl group «

The reaction of either 2- (2-imidazolin-2-yl) pyridine "of formula (I)" or N-substituted imidaeolinone derivatives, of formula (VIII), described and shown shortly before, wherein A represents CH2, CN or COOR1 provided that R has the preceding meaning, ooirn Sto cannot be an unsaturated alkyl group and B is R ^ CO or R ^ S0 ₂ and Y and Z cannot be an alkylamino, alkylthio or dialkylamino group, ea by excess a-chloroperbenzoic acid in the presence of an inert solvents such as methylchloride, at reflux temperature, yields the N-oxide of the corresponding pyridine derivative used as starting point. "The reaction can be shown as follows:

B

/ *! · Ro

Oh

-44n to which Λ represents ΟΗ ^, ON or COOR ^ previous ⁿ oim ir (; o Rj but may be unsaturated alkyl group; TV or ......

00R _{/ (} or SOpRc ·, R ^, Rg _t R ^, R ^ _t X, Y and Z are pre-d ·· ' ^: those phyto Ϊ and Z but may be an alkylamino, alkylthio or d-ιp' nmino group.

Hydrolysis of the N-oxide thus obtained by the use of Strong at least quo h of sodium sodium hydroxide. n lower «to the alcohol that it corresponds to Yesterday H I I 'in which B denotes H«

If, and preferably, the adlolone salts of hydrochloric acid, t; r, the ester of formula (I) in which A denotes COOR ^ and Rj Jo is other than hydrogen or cation-forming salt, and R ^, R £, X, ϊ: and 7 ou previously defined, solutions in organic solution k! 8This is motilenchloride, otar or the like. " Adding at least 1 equivalent of acid to the solution then leads to the desired acid addition salts. The reaction can be illustrated as follows

-15Iltt convenient mode of acid of formula (I) may be provm '· ·

5-H-imidazo 1 ', 2'and 1,2-pyrrolo 3,4-b pyridin-3 (2H), ·' formula (VII) in reaction with diochlohexylcarbodiimide ImReaction is preferably carried out using approximately the approximate one! amounts of carbodiimide in the presence of chlorinated hydrocarbons at a temperature between 20 ° 0 and 32 ° 0, Reverse reaction in the following ways

X

(I)

9lf-Jmidaz0 1 {2 * tl, 2 pyrrolo 3,4-b pyridin-3 (2H), 'i <n <um.Io (VII) ou isomers of imidazopyrrolpyridindione ίοι-.n'<piv.i.hoduo given. And especially eu useful for the age of jim, b »<- ¹ ? - (2-iuidazolin-2-yl) -pyridine derivatives of this formula (I)), which will be clearer on the basis of n><- · -b · Is ·, - 1. · ·

X

-16One general process for the preparation of a compound of formula (1) · catches the reaction of a quinoline anhydride of formula (XVI) with an optionally substituted <> 6-aminocarbonitrile formula (XVII), thereby yielding the emo monoamide of the hyalinic acid of formula (X) (X). This reaction is carried out at a temperature between <Approximately 20 ° C and 70 ° C, preferably between approximately 35 ° C and in an inert solvent, such as tetrahydrofuran, motile, d, ether, chloroform, toluene or dried · Acetic acid thus obtained ·· · '' Ee then cyclize to the proper. pyrrolpyridine poet · labeled with formula (XI) by heating the reaction with · excess acetic anhydride in the presence of a Catholic ^; larvae of sodium or potassium ethoate ·

- -17- /

Typically, this reaction is carried out by treating the reaction mixture with acetic anhydride, acetyl chloride, thionyl chloride or a similar compound and then heating this mixture between about 20 ° C and 100 ° C to give the pyrrolidine ae The formula of formula (XI) is treated with a strong acid such as sulfuric acid. Pyrrolpyridine cotauiid formula (XII) is obtained in this reaction - easy addition of a non-immiscible solvent such as methylene chloride, chloroform or the like is not relevant to this reaction, however, addition of such solvent is usually desirable. Said reaction is typically carried out at a temperature between about 10 ° and 70 ° 0.

The cyclisaoia of the compounds of formula (XII) or pyrrolpyridine acotamide gives imidazopyrrolpyridinedione, tricyclic formulas (111) which are intermediates for imidazolinyl nicotinic acids and esters, of the compounds of the present invention represented by formula (Ib).

The product of this reaction is still predominantly imidazopyrrolpyrindione (8%)

...... 'I' together with the isomer of the formula (lilac). The mixture of these two isomers in an isomeric, gives this ratio almost completely, pure nicotine products. The cyclization reaction is preferably effected at a temperature of 80 ° 0 to 15O ° O in the presence of a base such as sodium or potassium hydride or acids such as aromatic sulfonic acid and a solvent that builds an azeotropic mixture with water, allowing virtually instantaneous removal of water from the reaction mixtures at the moment of construction. The solvents that can be used are toluene, benzene, xylols and cyclohexane. Bases Koje the benefits of obuhvataju hydroxides of alkali metals, hydrides of alkali metals, oxides of alkali metal, tertiary amines As can su diizopropiletilumin,: -181.5-dlazobiciklo 3,4 nonene-5, l, 5-di ^a zobiciklo 5,4.0 -undekm5 , 1,4-Diazobiocyclo 2.2.2 octane, tetramethylguanidine, potassium fluoride and quaternary ammonium hydroxide, such as trimothy 1 bonzyl ammonium hydroxide and strongly basic ion-exchange and, in addition, acidic reagents which may be used include include aromatic sulfonic acids, such as? - toluenesulfonic acid, naphthalenedisulfonic acid and the like.

The eyes of the compounds of formula (XXJ) and formula (lilac) are then converted into the compound of formula (Ib) in the manner previously disclosed to the aid of alkali metal alkoxide and alcohol.

These reactions are schematically illustrated in reaction scheme I, wherein ^z ', wherein X, Y, Z, Rg, ®l are previously defined.

REACTION SCHEME I

X

(IX) (X) (REACTION SCHEME I - continuation)

H ₂ 80 ₄ base ->

(III)

-20 (REACTION SCHEME I - Score)

Another general method of aa to obtain a pyridine derivative of formula (I) involves the reaction of a quinoline anhydride of formula (XVI) aa with a suitably substituted 6-aminocarboxylic acid such as T-methylvaline, of formula (XIX), preferably in a ketone orifice, such as aootone a nitrogen atom to obtain an isomeric mixture of acids of formula (XX) and (XXI) · The mixture is then treated with acetic acid and anhydride and a catalytic amount of sodium acetate at elevated temperature to give dihydrodioxopyrrolpyridic acid of formula (XXII). The reaction of the acid thus obtained with thionyl chloride or thionyl bromide, in the presence of an organic solvent such as toluene, xylol, benzene and the like, at an elevated temperature of 80 ° C-150 ° C affords an acyl halide of the formula (XXIII) corresponding to the acid of formula (XXII). Treatment of this aoyl halide with excess ammonia then yields the dihydrodioxopyrrolpyridine acetamide of formula (IV). The reaction is preferably carried out in the presence of an aprotic solvent.

Reaction of acotamide of formula (IV) with 1,8-diazobicyclo 5 * 4.0 undoken-7 in an inert organic solvent such as toluene or xylene at an elevated temperature of between about 80 ° C and I25 ° gives imidazopyrrolpyridindione of formula (III) which possible '> ·

-21 heated with morpholine or the corresponding amine NHgR2 to give the salt 2- (2-imidazolin-2-yl) -clotinamide. This reaction is shown in reaction scheme IX »

REACTION SCHEME II

(XVI) (XIX)

X

YxJx ^ COOH

I I

CONH

COOH

R,

CONH-C-COOll

IR _?

Η ^χΛ ^ Ν ' ^χΛχ ΌΟΟΗ

(XXII)

-25.-. In another general method, 2- (2-imidazolin-2-yl) pyridine;

acids and the sharp formula (I) salt can be obtained by the reaction of 2-carboalkoxynicotinoyl chloride of formula (XIV), preferably in the form of a motile ester and preferably in the form of a hydrochloride salt, with the corresponding aminocarboxamide of formula (XIII). In the reaction with j, carbamoyl picolinate of formula (XV) is obtained whereby it is desirable for the reaction to be carried out under a nitrogen atmosphere, the Reaction dew point is usually maintained at a temperature below. During the reaction period, the carbamoyl picolinate, of formula (XV) thus obtained, may be suppressed to be dispersed in an inert solvent (nonproticin) such as .Ixylol or toluene and then heated from about 50 ^p 0 to 1 10 ^V C! with 1,5-diazobicyclic © - [5, AD ^] undec-5-Sn. The reaction produces a mixture of imidazopyrrolpyridinedione isomers of formula (XII) and (lilac), which can be used in a folk reaction without separation when the reaction mixture is treated with an alkali metal alkoxide, in the presence of alcohol, to give a mixture of imidazolinyl nicotinyl and imidazolinyl , The desired nicotinate of formula (ib) can be easily separated from picolinate by neutralizing the reaction mixture, preferably with glacial acetic acid, concentrating the neutralized solution, and chromatographing the resulting residue on an ailic gel using ether, using the procedures described above.

Similarly, imidazolinyl nicotinic kyelines can be converted to the corresponding alkali metal salt, ammonium salt or organic ammonium salts by the methods described above.

The preparation of acids and esters of formula (I) in this manner is shown schematically in reaction scheme III,

REACTION SCHEME III

(XV)

DBU xylol 't

(III) (lila) ά,

Ρ-1767/83 US-1/157 5986Ρ

REACTION SCHEME III - continued) r ₃ oh

R ^ ONa

(no angles nat) (Ib) ··. ^ 1 ^H z ^/ T00H (picol nat)

The 2- (2-imidazolin-2-ylquinol and carboxylate esters of formula (XXXVI) may also be obtained from the deoxypyrroloquinoline of formula (XXXVIII) wherein R1, Rg. X. L, M, Q 1 described, by clicking with a strong base, such as being 1,5-diazabi. -2δ-. :

cyclo ^ 5.4,03index-5 "®n (DBU) in the presence of an inert organic solvent such as xylene or toluene, this salt produces the crude imidazopyrroloquinolindione formula (XXXVII) · The reaction mixture is heated to a temperature between about 100 ° 0 and 150 ° C. _? i

The water is removed from the reaction mixture using a Dean-Stark water removal apparatus. At least one ♦ equivalent of the R ^ OH alcohol represented by formula (V) is then added, wherein R _z is a substituent having the above meaning but excludes hydrogen and cations forming the salts, and the resulting reaction mixture is heated to reflux at 100 ° C and 1βΟ ° Ο, and ester formula (XXXVI) is built. The reaction can be shown schematically as follows:

r ₅ o- - _Ml + (IV) (XXXVII)

-27L

in which Rp are Rg, Rj, X, L, M, Q and R? previously defined.

2- (2-imidazolin-2-yl) quinoline carboxylate aster formula (XXXVI) can also be obtained by olicisao of carbaryoyl phenol carboxylate ester, formula (XXXIX) with phospho-pentachloridoia, at an elevated temperature between about 60 ° C and 1 ° C. The reaction is usually carried out in the presence of an inert organic solvent such as toluene or benzene to give hydrochloric acid salt of formula (XXXVI) or 2- (2-imidazolin-2-yl) quinoline carboxylate ester hydrochloride. Treatment of such halogen hydrate with a base such as sodium or potassium carbonate then yields 2- (2-imidazolin-2-yl) quinoline carboxylate ester, formulas (XXXVI). The carbamoyl quinoline carboxylate ester of formula (XXXIX) used> in the above may be shown as follows:

in which Rj is described above but excludes hydrogen or a cation that builds salt, and Rp! <.>., X, L, M, Q and R? are threatening. -28described.

The 2 ~ (2-imidazolin-2-yl) quinoline carboxylate esters of formula (XXXVI) can also be obtained by cyclization of carbamoyl quinoline carboxylate ester having the structure shown by formula (XXXIX):

(XXXIX) in which Rj has the preceding meaning, except that they exclude hydrogen or cations that build eols, and Rj, Rg, X, L, M, Q, and K? have been described previously · The cyclization of the carbamoyl quinoline carbocylate ester is achieved by reacting that compound with a mixture of phosphopentachloride and phosphorus oxychloride. The reaction mixture is stirred for several hours at a temperature between approximately 15 ° C and 35 ° θ, 1 POClj is then removed in vacuo. from this reaction is dispersed in an organic® solvent such as toluene. The solvent was then separated from the resulting mixture, and the resulting residue was suspended in water heated between 80 ° C and 100 ° C. After cooling, the pH of the aqueous mixture was adjusted to 5-6 ea with sodium or potassium bicarbonate, and the product was extracted with methylene chloride to afford the 2- (2-imidazolin-2-yl) quinoline carboxylate ester of formula (XXXVI).

V

A quinoline ester of formula (XXXVI) in which R1 has the meaning given "but excludes hydrogen or cations that build salts, and Rp Rp X, L, M, Q and R? have been previously described, the salt is readily converted into its corresponding acid adioion salt, in the reaction of a dipped ester with at least one equivalent of strong acid. Use Lo ae strong mineral acids such as hydrochloric, sulfuric and hydrobromic acids, although organic acids can be used. In practice, it has been found that the reaction goes best where it is carried out in the presence of an inert organic solvent such as e Lar, chloroform, methylene chloride or aaea of these solvents Sulfuric acid pain is usually obtained by this process, but lower aliphatic alcohols are used instead of the solvents mentioned above. Preparation of 2- (2-imidazolin-2-yl) quinoline derivatives, formula (II), wherein A is C0t) H; B is hydrogen; W oxygen, a R ^ K · ,,

X, L, M, Q and R? have the meaning given that, provided that X, L, n, Q and Ry are not halogen or nitro groups, they may be carried out by hydrogenolysis of the benzyl ester of 2- (2-imidazolin-2-yl) quinoline carbolcsilate of formula (XXXVI). The reaction involves suspending the benzyl ester in an organic solvent such as those described for the hydrogenolysis of the benzyl ester of 2- (2-imidazolin-2-yl) pyridine series, of formula (XV), and thus treating the reaction mixture with hydrogen in the presence of a catalyst as which is palladium or platinum on carbon. Hydrogenolysis is usually carried out at a temperature between about 20 ° C and 50 ° C.

Acids of 2- (2-imidazolin-2-yl) quinoline derivatives, formula (II) in which A represents COOR; B is hydrogen; W oxygen, and Rp R ^,

- -50with the given meaning, but excludes hydrogen or cations that build salts, and Rp Rg, X, L, M, Q and H? have been described previously, with at least one equivalent of a strong aqueous base, such as an alkaline metal hydroxide aqueous solution, removed at 20 ° C and 5θ ° 0 at a temperature · The mixture is cooled and the pH is adjusted to 6.5 to 7.5 aa mlneial acid. Such treatments give the desired acid.

Dispute of 2- (2-imidazolin-2-yl) quinoline derivatives, formula (II), in which A denotes a COOR ^ j R ^ cation forming a salt; B is hydrogen; W oxygen and Rp Rg, L, M, Q and R? having the above meaning, may be derived by dissolving an acid of formula (II) wherein A is COOH; B is hydrogen; W oxygen and Rp Hg, L, M, Q and Rr have the meanings given above, in response to the solvent and by trituration of the mixture thus obtained with at least one equivalent of a cation forming salt. The reaction is practically in1, and as described for the preparation of pyridine, of formula (I), in which A represents COOR ^ and R ^ is a salt-forming cation.

It is understood that imdazolinylquinoline carboxylic acid and esters represented by formula (II) in which B denotes hydrogen may be tautomeric, it is also understood that when R 1 and R 8 denote different substituents of fora (II) and 2- (2-imidazolin-2-yl) quinoline derivatives and imidazopyrroloquinoline dione, of formula (XXXVII), - then the carbon attached to R1 and R8 is asymmetric, and the products (as well as the intermediate of these products) are present in the form 1 and also as dl forms.

Cyclization of imidazopyrrolchinoline acetamide, formula (XXXVIII) gives iraidazopyrrolinolindione, tetracyclic formula (XXXVII)

-51i of formula (XXXVlIa), which is in the intermediates of 2- (2-imidazolin-2-yl) quinoline carboxylic acids and esters of formula (II). The product of this reaction is the predominantly desired imidazopyrroloquinolindione, together with a small amount of isomers, of formula (XXXVIIa). Treatment of these isomeric emeae with an alkali metal alkoxide yields a generally isomerically pure quinolinecarboxylate product. The cyclization of aa is preferably carried out at a temperature of from 80 ° C to 15θ ° θ »in the presence of a base such as sodium or potassium hydride, or an acid such as aromatic sulphonic acid and a solvent that builds an azeotropic mixture with water, allowing practically instantaneous removal of water from the reaction mixture at the time of formation. The solvents used may be toluene, benzene _with xylols and cyclohexane. The bases that may be used include alkali metal hydroxides, alkali metal hydrides and oxides, tertiary amines such as au diisopropylethylamine, 1,5diazobiocycle §.4? nonen ^ 5il £ Mi ^a zobicyclo ^ .4.0jundecene-5, 1,4-diazobiocyclo (2.2.27octane, tetramethylguanidine, potassium fluoride, and quaternary ammonium hydroxide, such as trimethylbenzyl ammonium hydroxide and strong basic ionic acid, reagents that may be used herein include aromatic sulfonic acids, such as N-toluenesulfonic acid, N, 2-naphthalenesulfonic acid, naphthalenedisulfonic acid, and the like. Reactions are schematically attached to reaction scheme IV.

-52beakoiona scheme iv

(XXXVIII)

I

-33r (REACTION SCHEME IV - Continued)

R4O-alkali metal

COOR,

Q

JkA .K ⁷¹

'(XXXVI)

Several methods have been used to obtain the pyrroloquinoline acetamide given by formula (XXXVIII) · Preferably, the hydration of pyrrolinolin aoetonitrile, formula (ΧΧΧΧ) is treated with a strong acid such as sulfuric acid. This reaction yields pyrroloquinoline acetamide, formulas (XXXVIII). easy addition of a non-immiscible solvent such as methylene chloride, chloroform and the like is not essential for carrying out the said reaction, however, addition of the solvent to the reaction mixture may be desirable. Said reaction is usually carried out at a temperature of from 10 ° C to 7θ ° 0 · Alternatively, pyrroloquinoline acetamide, of formula (XXXVIII) may be rewarded with a Diels-Alder cycloaddition reaction of substituted antranyls, formula (ΧΧΧΧΙ) and dioxopyrrolin acoshiro tamide, of formula (ΧΧΧΧΙΙ ). These reactions are carried out at a temperature interval: below 13O ° C significant amounts of intermediate aldehyde, of formula (ΧΧΧΧΙΙΙ), are obtained, while at 130-200 ° 0, pyrroloquinoline aoethmid, of formula (XXXVIII) is formed. Alternatively to the intermediate aldehyde, formula (ΧΧΧΧΙΙΙ) may be isolated and cyclized in refluxing xylene in the presence of an acid catalyst, such as p-toluenesulfonic acid. This reaction yields the desired pyrroloquinoline aoetamide, formulas (XXXVIII). These reactions can be shown schematically in Reacolone Scheme V.

KEAKOION SCHEME V j 'i

(ΧΧΧΧ)

(XXXVIII)

(ΧΧΧΧΙ)

-ο.5-

(XXXVIII)

Many different. the reaction can be used to obtain pyrroloquinoline acetonitrile, formulas (ΧΧΧΧ), depending on the nature of the substituents L, M, Q and R? *

Pirolohinolin acetonitrill formula (ΧΧΧΧ) may be obtained by treating RA ₀ varajučo supstituisanog anhydride of the formula (XXXXIV) with corresponds juče eupstituisanim -aminokarbonitrilou, formula (XVII), that is built mixture monoamide of formula (XXXXVn) and acid, of the formula (XXXXVb) · This is the reaction is carried out at a temperature between 20 ° C and 7 ° C, preferably between about 35 ° C and 40 ° C, in an inert solvent, such as tetrahydrofuran, methylene chloride, ether, chloroform, toluene or the like. oiklize to the corresponding pyrroloquinoline aoetonitrile, indicated by formula (ΧΧΧΧ) · This is done by heating

1 *.

of the reaction mixture to a temperature between about 75 ° 0 and 15θ ° θ, with excess acetic anhydride, in the presence of a catalytic amount of sodium or potassium acetate. Basically, this reaction is cured by treating the reaction mixture with acetic anhydride, acetyl chloride, tlonyl chloride or a similar substance, and heating said mixture to a temperature between about 2O ° O and 100 ° G. · These reactions are schematically shown in reaction schemes VI. where Rp Rg » ^x » ^L »Q and ^ ^ma d ^{into the} equation ·

-36 are schematically shown below, and Rp Rg, L, M, Q and R? have the preceding meaning ·

(xxxm)

H *

aryl or

-CN (ΧΧΧΧ). · -57 Compounds of formula (ΧΧΧΧ) with electron donor aupstibuets at positions L, M, Q, and R ?, such as phyto are alkyl, alkoxy, allciltio, dialkylamino, hydroxy, and halogen, can be obtained by racation a suitably substituted o-aminobenzyl alcohol of formula (ΧΧΧΧΧΙΙΙ) or anthranilic acid, of formula (XXXXXIV), with chromo (or chloro) maleimide, of formula (ΧΧΧΧΧ). The reaction is carried out in the presence of a protic solvent such as phyto is isopropyl or t-butyl alcohol at 0 ° to 5O ° C to give hydroxymethylanilino maleimide, of formula (ΧΧΧΧΧΥ), or dioxopyrrolinyl anthranilic acid, of formula (XXXXXVI). Different base acceptorsP.ri salt can be used in these reactions, such as hydrocoids of alkaline earth motors, such as ΒβΒ ^, BaO or sodium acetate. However, in many cases the reaction is satisfactory without the aid of the base effector.

The oxidation of alcohol (ΧΧΧΧΧΥ) to aldehyde, .. 'of the formula (ΧΧΧΧΙΙΙ) salt can be accomplished by the use of a large number of oxidation reagents and is typical of the use of pyridine hydrochlorate in methylene chloride or of activated manganic oxide in t-butanol. Olicization of fortiul aldehyde (ΧΧΧΧΙΙΙ). ^ * ·. into pyrroloquinoline acetonitrile,. of formula (ΧΧΧΧ) is achieved by any of the methods previously described, for example by heating said aldehyde between 140 ° C and 200 ° C, in the presence of an aprotic solvent.

Oxidation of o-anilinocarboxylic acid, of formula (XXXXXVI) into acetoxyquinolia, of formula (ΧΧΧΧΧΥΙΙ) is carried out by the action of orchic acid anhydride, triethylamine and 4-dimethylaminopyridine at ambient temperature. Mild reductive elimination yields pyrroloquinoline acetonitrile, formulas (ΧΧΧΧ). Hydrolysis in warm aqueous acetic acid gives the compound of formula ((3 in kok · X; denotes OH, J 00 · ·

(ΧΧΧΧΧΙ)

L

(ΧΧΧΧΥΙΙΙ)

1.Δ.

rt ΤΙ *

(ΧΧΧΧΙΙΙ)

In addition, a further modification, useful for synthesis, which starts from aniline with electron donor substituents at positions L, M, Q and R? or aa by a chlorine or OP ^ function, so that the interaction of o-alkyl or arylthiomethyl 'aniline, of formula (ΧΧΧΧ1Χ) with bromomaleid, of formula (ΧΧΧΧΧ)., gives a smallimide, formula (ΧΧΧΧΧΙ), which is then oxidized to maleimide, of formula (ΧΧΧΧΧΙΙ) The latter is then oxidized in acid-catalyzed reaction 1 to give pyrrolinoline aoetonitrile, of formula (ΧΧΧΧ), Reactions

-39REACTION SCHEME VII - continued)

This synthesis is particularly effective when the substituents L, tl,

Q and Ry are electronegative, for example in the case of halogens, nitro, CF3, SOgCH2 and ON groups. A modification of this process involves the reaction of an o-aminoacetal, of formula (ΧΧΧΧΥΙΙΙ) with a suitably substituted maleimide, of formula (ΧΧΧΧΧ) or dioxopyrrolin aoetamide, in the presence of an aprotic solvent, as xylol or toluene at a temperature between approximately 5θ ° θ and 13θ ° θ · These reactions are schematic are shown as follows:

(X v 7 i <\ (χχχχνιιΐ)

1. Δ

2. H ⁺

A preferred route for the synthesis of pyrroloquinoline acetonitrile, of formula (ΧΧΧΧ), is Diela-Alder thermal thermal loading reaction of a suitably substituted maleimide, formula (XXXXVI) with a suitably substituted antranyl. In this reaction, X must be hydrogen. The outcome of this reaction depends on the reaction temperature. The preferential compound of formula (ΧΧΧΧΥΙΙ) is obtained at about 55 ° θ · As the reaction mixture is heated further, an int. »X— mcder, of formula (ΧΧΧΧΙΙΙ), denotes an aldehyde, at temperatures between 55 ° C and 150 ° C. If the reaction is carried out in the presence of an aprotic solvent such as o-dichlorobenzene, and the reaction mixture is heated to between 140 ° C and 200 ° C, pyrroloquinoline acetonitrile, of formula (ΧΧΧΧ), is obtained. The reaction is shown in reaction scheme VII.

reaction scheme VII

L

R, o

CN (ΧΧΧΧΙ)

R,

(χχχχνι) (χχχχνιι)

REACTION SCHEME VI

(m)

-42dinom gives iodine in which X stands for chlorine.

These reactions are shown in reaction scheme VIII.

(χχχχχνι) oxidation.

,. + 5 (χχχχχν) oxidoxia

ΓυυυυτττΊ

Γγγγγγνττ \

(ΠΠ)

The second pathway to 2- (2-imidazolin-2-yl) quinoline compounds of formula (II), especially useful for the synthesis of analogues in which group A is changed, is based on the use of 2- (2-imidazolin-2-yl) quinoline , of formula (ΧΧΧΧΧΙΧ). This intermediate is obtained from quinoline-carboxylic acid, formula (ΧΧΧΧΧΥΙΙΙ), which is converted to acyl chloride or anhydride, and then treated with any appropriately substituted << - aminocarbonitrile, formula (XVII) to give nitrile, formula (ΧΧΧΧΧΧ) or with an aminoamide, of formula (ΧΧΧΧΧΧΙ) to give the carboxanidoamide salt, of formula (χΧ' ·) · 'Cyclization of the dipped carboxamidoamide is carried out by the methods discussed above, although cyclization with sodium hydride, in the presence of xylol, is desirable. The introduction of different groups A is made possible by treating 2- (2-imidazolin-2-yl) quinoline of formula (ΧΧΧΧΧΙΧ) with the aid of metal reagents. Most soil organisms! of reagents has some effect when »C is used by two moles in addition to the dianion buildup, but in the yield and reaction content depends on the nature of the organometallic reagent, the reaction solvent, the reaction fluid and the electrophile used to stop the reaction. In practice, organometallic reagents such as phyto bu alkyl lithium are preferred, wherein the anion is formed with methyl, n-butyl, sec-butyl and tert-butyl lithium. Penyl lithium and lithium diisopropylamide can also be used. Solvents must be aprotic and diethyl ether preferred. The reaction temperature-used fabrications for civil dianjona kroču from -? 8 ⁰ C to 0 ° C, but preferably are made of -30 ° C to -10 ° C. The interruption of the reaction with ea by the electrophile is usually set at -? 8 ° C to + 20 ° C. If necessary, then treatment with acid occurs. All reactions are inert gas. Examples of reactive electrophiles include: CO ^, CICC ^ C (CH ^ gNCHO, CHjCHO, ΟθΗ ^ ΟΗΟ, CH ^ I. The corresponding substituents for A in formula (Ila) are COOH, COOCHp CHO, CH (OH) CH ₅ .

ΟΗ (ΟΗ) ΟθΗ ^ and CHj. After stopping the reaction with the electrophile, the products can be modified. Thus the aldehyde (A-CHO) is obtained

After stopping reactions with DMP, it reacts with hydroxyluinine to form an oxime. "This process is also useful for the synthesis of a compound in which A stands for COOH when the dianion is treated with carbon dioxide.

*. *

Aren't all the substituents X, L, M, Q and H? compatible with this process using organometallic compounds. Thus, if the aforementioned substituents are Br, I, or sometimes fluorine, then the reaction of elimination of these groups as well as the 'replacement of the quinoline protons in position 3' occurs at the same time · Chlorine is, however, compatible with this process, when L, M , Q or R? methoxy, then the anion can be built in the ortho position relative to the methoxy group. The reactions described above are schematically shown in Reaction Scheme IX.

7 & δ-

(ΧΧΧΧΧΧΙΙ) (ΧΧΧΧΧΙΧ)

-.- - ^ 47Some functional groups A are prepared with an alternative approach. According to the pyrroloquinolindione reaction of formula (XXXVII) aa ttJOM * gives 2- (2-imidazolin-2-yl) quinoline esters of formula (XXXVI). In the case of formula (II) for compounds in which A denotes a 'GOifiiCi ^ CHgOH group, cyclization is carried out to the oxazoline group in the reaction of the above-identified compound with triethylphosphite in refluxing xylene · Derivatives of formula (II) in which A gives a-CONHg' or translated into the corresponding cyano derivative in which A stands for ON by dehydrating the -GONHg function.

Most compounds containing L, M, Q and R? substituents can be obtained by the steps previously written; however, the amino alkylamino and dialkylamino compounds are conveniently obtained by the derivative alkylation of the corresponding NOg substituent at the L, M, Q or Ry position. Alkylsulfonyl compounds are most readily obtained by mild oxidation of the alkylsulfonyl group at position I, M, Q or R? at 0 ° to 20 ° C, using m-chloroperbemzoic acid. Under these axes, the N-oxidation of quinoline nitrogen is minimal. The oxidation of quinoline to N-oxide can be carried out before N-protecting the imidazolone ring with for example the COCH ^ group; The N-ocation. May then be assisted by porsuric acid or trifluoropersiracetic acid at elevated temperatures if necessary.

2- (2-imidazolia-2-yl) pyridines, formulas (I), 2- (2-imidazolinone;

** il) quinolines, formulas (II) and imidazoplrolopiridinedione and imid pyrroloquinolindione formulas (III), the compounds of the present invention are extremely effective herbicides useful for controlling a large number of grass and woody, annual and perennial monocotyledonous and dicotyledonous plants.

= -48 yen strong, in relatively small doses, from 0.016 to olto 2 hectares per acre, depending on the compound used and the treated area in which the plant grows.

It has been found in the alcea that generally 2- (2-imidazolin-2-yl) pyridines, formulas' (I) are most suitable as broad-spectrum herbicides, whether used pre-emptively or after an emergency in a weed control site . It is not intended to say to the eu team, however, that all pyridines of formula (I) are indiscriminate.

In fact, some 2- (2-imidazolin-2-yl) pyridines, in particular the formula (I) which is substituted in five places, as well as the pyridines, of formula (Ia) and are selective for the pods and especially for the pods soybeans. Similarly, 2- (2-imides, Formula (I) ₉ and (II), zolin-2-yl) quinolines have been found to be mainly selective herbicides and are particularly effective in controlling unwanted weeds in the presence of leguminous plants such as au pods soybeans. However, certain compounds of formula (I) and (II) are less selective than others in the series.

Also found were some 2- (2-imidazolin-2-yl) pyridines and

2- (2-imidazolia-2-yl) quinolines, formulas (I) and (II) are effective as defoliants for cotton when applied in amounts from 0.016 to 4.0 kg / ha. At doses not exceeding approximately 0.01 kg per hectare, certain pyridines and quinolines, formulas (I) and (II) have been found to act effectively to increase the thickening of legumes

plants and affect the early ripening of the grain.

Pyrrolopyridine acetonitrile, formulas (XI), and pyrrolopyridine acetamides, formulas (IV), pyrroloquinoline acetonitrile, formulas (form) and pyrroloquinoline acetamides, formulas (XXXVIII) are useful as intermediates for the preparation of herbicides of formula (I) and (XI) denote 2- (2-imidazolin-2-yl) pyridines and quinolines and herbicides of the formulas (III) and (XXXVII) denoting imidazopyrolopyridinedione and imidazopyrroloquinolindione · and

As imidazolinylpyridines and quinoline derivatives, the Te (I) and (II) forum in which R denotes a salt-forming cation, solution in water, can be readily prepared in the form of a dispersion and applied as a diluted aqueous spray for application to the leaves. plants or soil containing growing parts of plants. These salts may be present in the form of a liquid concentrate.

2- (2-imidazolin-2-yl) pyridines and quinolines, formulas (I) and (II) and imidazopyrrolopyridinedione and imidazopyrroloquinolindione, fory. ule (III) and (XXXVII) can be prepared as a wet powder, hail, so-called conoentrate, emulsion concentrate, granular preparation, and in the like.

The wet powder can be obtained by pouring together 20 to 45 $ (wt) of a finely separated carrier such as kaolin, bentonite, diatomaceous earth, atapulgite and the like, 45 to 80 wt% of the active compound, 2 to 5 wt% of dispersant reagent such as sodium lignosulfonate and 2 to 5 weight percent non-ionic surfactant (surface reagent) such as octylphenoxy polyethoxy ethanol, nonylphenoxy polyethoxy ethanol and the like.

A typical liquid preparation can be obtained by mixing 40 weight percent of the active ingredient with about 2 weight percent. percentage of zealotous agent such as 3 wt

-50zionic reagent such as sodium lignosulfonate, 1 weight percent polyethylene glycol and 54 weight percent water.

Typical emulsilone conoentrate knives are obtained by dissolving 5 to «

t weight percent of the active ingredient in about 65 to 90 weight percent N-methylpyrrolidine, isophorone, butyl oelosol, methyl acetate and the like, and a dispersion of 5 to 10 weight percent of a non-ionic surfactant such as alkylphenoxy polyethoxy alcohol. This concentrate is dispersed in the liquid for use as a liquid spray.

When the compounds of the present invention are used as soil treatment herbicides, then the ee compounds can be prepared and applied in the form of granules. The preparation of the granular preparation can be achieved by dissolving the active compound in a solvent such as methylene chloride, N-methylpyrrolidine or the like by spraying the solution thus obtained onto a granular carrier such as sand, corn-piston powder, atapulgite, kaolin and the like.

The granular preparation thus obtained typically contains 3 to 20 weight percent of the active ingredient and about 97 to 80 weight percent of the granular carrier.

Yes) ibl facilitated further understanding of the invention, the following examples are provided which primarily illustrate certain specific details of the invention. The invention is not judged to be limited on the basis of this unless defined by the claims. Unless otherwise specified, all parts are by weight »

-51PRIMBR 1

Preparation of 5,7-4ihydro- [Z-isopropyl- N - methyl-5,7 ~ dioxo-6 'pyrrolo [3,4-b] pyridine-6-acetonitrile

To a stirring solution containing 212 g of quinoline anhydride '- * 3

95θ cnr of methylene chloride was added at a moderate rate of 167 C 2- · ιο2,3-dimethylbutyronitrile. The mixture has reached the key point?. ·;

and after the addition of a quarter of aminonitrile and, then, the rate of dr. '',, it adjusts to maintain this temperature. · After the addition of solution r; · refluxes for a further 4 hours. The solution is cooled, filtered and centered on the oil. This oil is dissolved in 95θ c »anhydride / ·. Acetic acid, with 6 g of anhydrous sodium acetate λ added.

The * mixture was distilled until the vapor temperature reached 118 ° C when; o Reflux heating continues for 3 hours. The mixture was concentrated in vacuo, the residue dissolved in 5θ0 ca? toluot concentrates again. 'These are repeated. The residue is mixed with 'porridge with a mixture of ether and hexane and a crude crying product'. are expensive (349 g). This is dissolved in 7 ° θ cm ^ motylene chloride:? ': And strained through a column containing 70θ S silica gel, and is eluted with methylene chloride. Concentration of the stripped fraction gave 258 g of the desired product. Analytically pure sample, m.p. 95-9θ ° Ο, can be obtained by crystallization from ether and aotylene chloride.

<· V

Using appropriate amino nitrile and quinoline arch? .-. and in this process, the following pyrrolopyridines are synthesized:

-52-:

X

Y \ M Λ? N-C-CN Cf. X + * » 2 ^X «a X 1 0 1 ¾ Y Z mp ° c ch ₃ ch ₅ H H H • 119-123 ch ₅ <? 5 H, '/.V,' H H 95-97 ch ₅ _ Δ H H H 69-73 CH-. 3 CH ₂ CH (CH ₅ ) ₂ H H H oil - (CHg) ₅ - H H / H 85-87 ^C 2 ^H 5 c ₂ h ₅ H t H. H 71-72,5 ch ₅ CH (CH ₂ ) ₂ ch ₅ H H 129,5-1310 CHj CH (CH ₂ ) ₂ H H och ₅ 108-110 CH, 5 CH (CH ₂ ) ₂ H H Cl 94-96

-55- ^:

EXAMPLE 2

Preparation of 5,7-Dichloro-N-Z-Isopropyl-Z-methyl-5,7-dioxo-sickle, plof, 4-bJ pyridine-6-acetamide

In 5J0 cm ^ of concentrated acid, add drop by drop to the dream. 298 g of finely ground nitrile, so that the temperature: '· did not rise above? 2 ° C »After addition, the temperature ec is adjusted to 60-65 ° C and maintains an hour and a half · The mixture is cooled and the rock is stopped with ice and finally diluted to 4 liters, Ke ¹ /: adding 454 g of sodium acetate and cooling to 0 ° C in this?

The mixture was filtered and the solid was collected and washed 2 ™ with 5θθ cm ^ of water containing sodium acetate, then with water to remove all sulfuric acid. The substance is dried to give 289 6 products, m.p. · 17θ-178 ° Sup · The substance is synthesized in a similar manner that is analytically pure having t «t. 1 190 ° C.

Using the appropriate pyrrolopyridine acetonitrile in this process, the following pyrrolopyridine acetamides were synthesized.

^Β ι H ₂ X I ; z mp ° C ch ₃ ch ₃ H H H 203-5 CH, H H 'H 158-157 CH, H H ·· H 1 $ 5-18 <

EXAMPLE '? / _{! ff} j

I i

i

Preparation of 5-Isopropyl-3-ethyl-5H-imideBO- [1 *, 2ζ: 1,2Z] pyrrolo 3,4,4 3 pyridine-2- (3H) 5-dione

A mixture of JO g amide and 45 © cm ^ toluene is already heated in DeanStark apparatus for removing traces of water · 10.1 g of 50% sodium hydride suspension in mineral oil is added to the cooled mixture and the mixture is heated at reflux for 23 hours. " The hot solution is filtered, concentrated in vacuo and crystallized. The mineral oil was then decanted and the solid was washed with a mixture of hexane and dried in vacuo to give 4J, 5 g of product, which, by NMR analysis, was 90% desired! isomer II and $ 10 unwanted isomer of Il. A pure sample of isomer II can be obtained by crystallizing the crude product from hexane and methylene chloride, mp 107-115 ° G.

Cyclization can be done either with the help of a basic reagent of sodium or potassium hydroxy, or with the help of acidic reagent ^ t-toluenesulfonic acid in toluene as a solvent. are directly used for the synthesis of nicotinic acid esters.

Using the appropriate pyrrolopyridine carboxamide, the following imidazopyrolopyridines were synthesized.

<

R ₂

CH _? ° 2 ^H 5

ch (ch ₅ ) ₂

X Y z ·. Ό • l «- (· <·« · »« «« || «

H. _t HH 'v

H H H

H H H

H H H 125. 50

H H. OCH ^

EXAMPLE 4 ^J

Preparation of 3-Isopropyl-5-H-imidazo [2 *, 2 *: 1,2 J -pyrrolo [3,4-6] pyridine-2 (3H) -dione

Mixture containing 52 g of 5- E (1-carbamoyl-1,2-dimethylprop? 1? Picolinate, 1,77 cm ?, 5-iiazobicyclo [5? 4? O3-undec-5? Er: .au 400 cm ^ xylol was heated to the temperature refluktovanjc. u Doan-Stark-wrapping apparatus for 2 h. a mixture of the koncentrujo u 'kuumu and the residue chromatographed on 400 g baznog ^{aluminijxrn-o} .s5.da (alumina). a mixture reap yen product eluted with moti?. ·· .: ·· chloride and uses without purification.

s /.-56-.

EXAMPLE 5

Purification of the methyl 2- (5-isopropyl-5-methyl-4-OxQ-2 ~ imide with o lyre ~ 2- yl) nicotinate

This process involves the construction of triocyclic compounds at Measure 5 14, without isolation, and the direct construction of nicotinic acid esters:

ΡΒ'ϋ in three cycles č · a.

xylol intermediate

A mixture of 25 g of amide and 1 cm ^ l, 5-diazobicyclo- [5 * AO] undec-5ena (DBU) in 5θθ xylene was heated at reflux for 1 hour in a Dean-Stark apparatus. · The mixture was cooled slightly, ^J 7 remove the water extraction apparatus, add 100 cnr of anhydrous methanol, and heat the mixture at reflux for 3 hours. The solvents were then removed in vacuo and the product isolated chrenatographically as described in Example 5 to give 13.65 g of product, t, t. 120-122 ° C identical to Example 5 »

EXAMPLE 6,

Deactivation of methyl 2- (5-isopropyl-5-methyl-4-oxo-2-imidazolyl; -2-yl) nicatinate. Procedure A (Reaction scheme p, ¹⁰ »- ¹ ¾

A mixture of. 13.65 β of nicotinate and 9.69 g of phosphorus pentachloride in 110 era ^{5 of} dry toluene were heated with stirring at 80 ° C. After 1 1/5 hours, the thick mixture was cooled, evaporated and the solid was washed with ether and dried. This represents the hydrochloric acid salt of the desired product. This salt is dissolved in 60 cm ^; neutralize rn with sodium bicarbonate, the resulting precipitate separates the strainer, 1; steamed with water, dried in air, and obtained the product identiorr. to the one synthesized in Example 5 ·

Procedure B

ΧίΑ

COOCH,? ^H 3

C0NH - ^ - C0NH ₂ ch (ch ₅ ) ₂

1. PCl ^ / POCl ^

2. H ₂ 0 *

A mixture of 5 e nicotinate and 7.1 g phosphorus pentachloride in 40 cnr phosphorus oxychloride was stirred at room temperature overnight. The phosphorous oxychloride was removed in vacuo, the residue suspended in 40 cm &lt; ^{5 &gt; of} toluene and concentrated again. This is then repeated. 40 cm <^{5> of} water was added to the residue and the mixture was heated to reflux temperature and then left for 1 hour. After cooling, the mixture is triturated with methylene chloride and the extract is dried and concentrated at

-60-.

yielding 1.05 g of the desired product. The pH of the aqueous phase and the extraction with methylene chloride were adjusted to 5-6 by means of a nol trium bicarbonate solution and the mixture was again extracted with methylene chloride. The dried extract was concentrated and the residue. then crystallized to give 2.65 g of the desired product identical to that of Example 5 ·

The following nicotinic acid esters have been synthesized using '···!

one or more of the following procedures:

--61-

h i Rg X X Z_ 4.1. “Mr. CHj. CH ₅ ^c 2 ^a 5 H H H 126.5-128 CH ^ CH '<<_> ch ₅ CH (CH ₂ ) ₂ H H H 101-- ' ch ₅ -r -r H H E 16 · 5.3 - 'CH ₃ 1 CHgC ^ c n -ch- (ch ₂ ) ₄ - • H H H 117- Ό ch ₃ ch ₂ c ₆ h ₅ . -CH- (CH2) ₄ - H H H 146.,; .- 151 ch ₅ • CH ₂ CsCH ch ₅ CHj H H H 171-175 CH .. 2 ch ₅ OHj H H H 168-; 60 ch ₂ c ₆ h ₅ ch ₅ CHj H H. . H 162-114 ch ₂ c ₆ h _5z ch ₅ H H S < 116- / 10 CH ₂ C5CH · CH, 5 ^c 2 ^h 5 H H H 138-11-0 - ^ 25- ° ch ₅ ch (ch ₅ ) ₂ H H H 55-57 -c ₂ h ₅ ch ₅ CH (CH ₂ ) ₂ H H H 72-75. CH (CH ₂ ) ₂ H H H 90-02,5 “Oh ·. ch ₅ ch (ch ₅ ) ₂ H H  H 12Ο, 5-1ί -ch (ch ₅ ) ₂ CH, 3 - ch (ch ₅ ) ₂ H H H o: · _f, 7 i -ch ₂ c ₆ h ₅ • ch ₅ CH (CH ₂ ) ₂ H H H 122-125

 · X X Z j, p In L · ch ₅ oh (ch ₅ ) ₂ H H H ·> Ί Ί - * .J . , oii ₀ och, - 2 J oh ₅ OH (CH2) ₂ H H H GC-S * 5 - '/ huch ₂ ' v < CH, p oh (ch ₅ ) ₂ H H H m he ... · - '> ..? r :: -giuch ₂ ; / 'i CH, P CH (CH ₂ ) ₂ H H H - »* l ^{1 1} « *? , -CwCH _o ,. · I 2 CH, P ch (ch ₅ ) ₂ H H H. 92--100 OH, · 5 • CK-C ... CH | ch ₅ CH (CH ₅ ) ₂ H H H. • ''. '; 0 7 · 1 '; -CH.OHOH. -. · .. p ch ₅ 0H (CH ₂ ) ₂ H H H 07 · -39 · * ch ₅ , ch (ch ₅ ) ₂ H H H 12 -: - 126 0 CH, P ch (ch ₃ ) ₂ H H H . -_o . · 'J ¹¹ —Λ '3? 37 ⁿ CH, P ch (ch ₅ ) ₂ H H H 77-7-7 '· ⁽ ' Λ CH, P CH (CH ₂ ) ₂ H H H 115,3-1 CH, P CH ^ CHj) ₂ H H H 72- 78 > *. CH, oh ₂ ch (ch ₃ ) ₂ . H H H 92-91 -Γ ,, ί ^ -η CH, P ch ₂ (ch ₃ ) ₂ H H H 31-37 o; i ₀ csch f ' ch ₅ chch (ch,) ₂ H H H 123,5-1 , ”» R r s? - '- ·, 9 · CH, P < H H H 123-151 ^C? 2 ^C 6 ^H 5 ch ₅ H H H 111-113 / 1 «» 5. OH, P ch (ch ₃ ) ₂ H H OCH, P 151-155 • _? -CH-CH-C ₇ H ₁₅ «.n CH, P CH (CH ₂ ) ₂ H H H. 'il.jc , -C (Cl) -. CH ₂ b *. CH, P ch (ch ₃ ) ₂ H H H 75-77 'Γ5 ~ ^η CH, P ch (ch ₃ ) ₂ H E H vi.η e J .. (OH ₅ ) CH-CHCH ₅ CH, P CH (CH ₃ ) ₂ H H H oil o

^{, R} S h. X Y., Z t. ^r 'i t ft 0' (' •. <CK ₂ ) ₅ - .. -. H H H Ί f <Ί / 1 <? . <· '· Ί0Η ₃ ) _? CH ₅ CH (CH _? ) ₂ H H H 77,5-79 ^f - (ch ₂ ) ₅ H H H 117-129 /: - · .ΌΗ ₂ 0Η. * ch ₅ ch (ch ₃ ) ₂ H H H cu :. '' ¹ 2¾½. c ₂ h ₅ ^C 2 ^H 5 H H H 114,5-11 <· (. ·: ₇ >C; CH · / ce ₅ · οη (οη _? ) ₂ H H H 128-152 · ₂ '· ⁺ (ΟΗ ₃ ) ₃ χ-. ch ₅ ch (ch ₃ ) ₂ H H H 165-175 (. ·, ^c ž? 5 c ₂ h ₅ H H H 152,5-15 C (HH ₃ ) _? C = CH ch ₅ ch (ch ₃ ) ₂ H H H 104-105 <. · ./Ι,οη ch ₅ H H H 122-11; · </ CII - (CH ₂ ) - 0 H H 164,5-16 % CH, 5 CH (CH ₂ ) ₂ CH, 5 H H 114-12.5, c ₂ h ₅ c ₂ h ₅ H H H 155.5 15 ch ₅ ch (ch ₃ ) ₂ H H H 111-115  : .// ^ -Cl CH, 5 ch (ch ₃ ) ₂ H H H 156-158 <; ,, _ // '0piO ₂ ch ₅ oh (oh ₃ ) ₂ H H H 151,5-15 C: _Λ ς000Η2.f ··. · '.'.> ch ₅ CH (CH ₂ ) ₂ H H H 104-2.08 C- ^ K-O Objective CH, 5 ch (oh ₃ ) ₂ H H ' H 95-97 ClM / CH, Z c; , C! F _o CH ₂ CQ0C ₂ H ₅ ch ₃ CH (CH ₅ ) ₂ · H H H ul, jo c: Coh ^ coocHj CH, 5 CH (CH ₃ ) ₂ H H H 155-155 C '. '7 CH, 5 ch (ch _? ) ₂ H Nr H 122,5- C. / U, CiICOOC ₂ H ₅ CH, 5 Ch (ch ₃ ) ₂ H H H oil <^ pCOOCHj. ch ₅ CH (CH ₅ ) ₂ H .. H H - '•• C * c; / <Q> ~ 0 (OH ₃ 0 ₃ CH, 5 ch (ch ₃ ) ₂ H H H loo-

\ π

0., /; ii _? CU-C (CH ₅ ) ₂ C ^f ., C :-( 0n) CH ₂ 0H

CH,

CH,

CH, ch (ch ₅ ) ₂ ch (ch ₅ ) ₂ ch (ch ₅ ) ₂

X Y Z tet / 'C

HHH 107-100 ch ₅ H h 130-132

HHH II5-II5 ch ₅ ch ₅

- c ;; (c ₆ h ₅ ) c, o0ch ₅ · 0} ₂ ΰ1 ' ₂ 0 (0Η ₅ ) -0Η ₂ (C ^) _q CH.CH ₂

C]> (CH ₅ ) C ₆ H ₅

CH (CH ₅ ) ₂ hhh

CH (CH ₅ ) ₂ hhh

CH (CH ₅ ) ₂ 'HHH oil oil

73-73

CH (CH ₂ ) ₂ . HHH oil ch ₅ , oh (ch ₃ ) ₂ ch ₅ oh (ch ₅ ) ₂ ch ₅

CH, • ch (ch ₂ ) ₄ 'ch (ch ₃ ) ₂ ch (ch ₅ ) ₂

//.

CH ₂ & = Clt

CH _o C00CH _o CH,, 2 3

CiUCOOH. CB ₂ CQ0CH ₂ C ₆ H ₅

CII / 300.11

CII-

? h (ch ₂ ) J

CH,.

-gH (CH ₂ ) ₄ ch ₅ “ch (ch ₅ ) ₂ ch ₅ ch (ch ₅ ) ₂ ch ₅ - ch (ch ₃ ) ₂ ch ₅ ch (ch ₅ ) ₂ ch ₃ ch (ch ₃ ) ₂ ch ₃ ch (ch ₃ ) ₂

H H H

H H H ·

H H E

H H H

H H H

H H H

H H H

H H Cl

H H H

H H H

H H H

H H H

H H H ul jo oil ul j o oil

122- 124

123- 125

132-134,5

105,2-104

86-90

187-189

121,5-122

106-110

110-112 [oll ^ + 24-, 43

-65- ..

2i ^ 2_ X Y With tet- ch ₃ ch ₅ ch (ch ₅ ) ₂ H H h 110,5-: Qij - D " ol, about ₆ h ₅ ch ₅ ch (ch ₅ ) ₂ H H H 102-1 ·. 7- * oh ₂ c ₆ h ₅ ch ₅ oh (ch ₃ ) ₂ H H H 104-1 ' -CH, 2 ch ₅ ch (ch ₅ ) ₂ H H N (CH ₃ ) ₂ 184.7-

EXAMPLE 7 J

Preparation of the methyl-2- (5-isopropyl-p5-methyl-4-ox3c-2imidazolin-2-yl) nicotinate addition salt with hydrochloric acid

To a stirred suspension containing 3.0 g of the ester of Example 5, enough methylene chloride was added to 40 cc of ether to give a solution. The dry chlorine o hydrogen was then allowed to enter the solution for 20 minutes. After 1 hour, the mixture is filtered to separate the product which is washed with ether and dried; 1.90 g of analytically pure hydrochloric acid salt are obtained and the melting point is 195-196 ° C.

-66 EXAMPLE 8 /,

Preparation of 2- (5-butyl-2-pyridyl) -5-isopropyl-5-methyl-2-yridazolin-4-one

Ώ ° ζ ,. ^Η 9

Nf '^ CONH-C «J ch (ch ₅ ) ₂

COHH,

The suspension of sodium hydride (2.4 g) in 25θ cm &lt; 2 &gt; of dry weight is stirred at reflux temperature in Dean-Stor. '; * This apparatus. 26.52 g of diamide is added slowly to this mixture. · After addition, heating is continued for 1.5 hours. After overnight aging, the reaction was quenched with water, pH adjusted to 5 aa with hydrochloric acid and the layers separated. The aqueous phase was further extracted twice with ethyl acetate, the organic layers collected (combined), washed with brine, dried and concentrated. The residue was crystallized from hexane to give the pure product m.p. 60-62 ° C.

Following virtually the same procedure, the following u * imidazolinones were synthesized.

-67X Ϊ Z

Η ° 6 ^Ξ 5 ^Η

Η Η CH,

Ρ

CH * CHj Η

NO „NOg · Η

-68-,

EXAMPLE .9 v - \ Λ

4 [2- (5-Isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl) nicothionyl 3 morpholine is obtained

isomer

z

The cyclization of the amide is carried out by heating 7.83. g of amide in 150 toluene and 0.45 ca »^ 1,8-diazobicyclo 5» 4,0 ondec-7-ene v. Dean

Stark water separator for 2 hours as described in Example 4. Part of the water separator was separated by adding 4 cm- ^{7 of} morpholine and heating continued for 3 hours. The mixture was concentrated and the residue was chromatographed on silica gel overnight with ethyl acetate. The product is eluted first and crystallized from the ether-hexane mixture to give the pure amide, mp 143-145,5 ° θ »

Using the appropriate amino instead of morpholine synthesize ·. pale amides:

-CH ₂ C = CH

mp ° c

171,173.5

227.5- 228.5

174.5- 175.5

-70PRIMER 1Q

Preparation of 1,3-dihydro-N-isopropyl-N-methyl-1,3-dioxo-2-pyridin-1-C3,4-bJ quinoline-2-acetonitrile

Antranyl (59.6 g, 0.5 moles) was added dropwise under nitrogen atmosphere with stirring for 45 minutes in a refluxing solution of -isopropyl-methyl-2,5-dioxo-3-pyrrolin-1- acetoniiri la in o-dichlorobonsen (450 cm ^). After 18 hours the reaction is allowed. and cooled and methylene chloride was added. This solution was applied to a silica gel column (7.5 cm column) and eluted with methylene chloride. Concentrate the eluate to 5θθ ^cm and add hexane. A precipitate is built, the solution is treated and the precipitate is air dried; 110.6 g (75%) of a light brown substance are obtained. Crystallization from ethyl acetate-hexane gave pale yellow crystals, tt 195-193 Analysis: calculated (for C ^ r ^ H ^^ N ^ Og) θ 'θ ^, θΐ »H,. 5.15; N, 14, Found: C, 69.57} H, 5.15; N, 14.43.

The following products were synthesized under similar conditions (Table I)

-7'1Procedure Β

Oiklization o-formllanilin.o-aaleimj.da

Solution of N- (1-cyano-1,2-dimethylpropyl) -2 - (o-formylanilino) maleimide (7.19 g, 0.023 mol) in xylene (3θθ cap) containing Δ-toluenesulfonic acid (0.3 g , 0.0016 moles) is heated at reflux temperature for 4 hours and a Dean-Stark trap is used to collect the eliminated water. 7.5 cm in length · The ethyl acetate fractions are combined (after elution) to give a substance, m.p. 195-195.5 ° θ, in an amount of - 5.51 g (81%) representing 1,3-dihydro-eye-isopropyl-N-methyl-1,3-dioxo-2-H-pyrrolo, 4-bJquinoline -2-acetonitrile.

Other compounds synthesized by this procedure are given in Table I.

~ '? 2'

TABLE I

<1 1 h X L  M Q h Procedure mp _e ° C «: U. CH (CH ₅ ) ₂ H H no ₂ H H A 250-232 , · '· T ch (ch ₃ ) ₂ H H H N0 ₂ H A 260-261 <'L < o s;., / oii (ch,) ₂ ch (oh ₅ ) ₂ H H M ₂ H H H H H H no ₂ A Gi i -i- ch (ch ₅ ) ₂ H Nr H H H . A / »1 '·“ · * r ch (ch ₅ ) ₂ H Cl H H H A, B 139.5-142 CH (CH ₂ ) ₂ H H CF, 3 H H B Cii. 2 CH (CH ₂ ) ₂ H H H Cl H B 188 Cii, 5 ch (ch ₅ ) ₂ H H CH, 5 H H B Cii ,, 0H (CH ₂ ) ₂ « H H H ch ₅ H B 186-190 CM. ch (ch ₅ ) ₂ H H H H ch ₅ B 'Ί 1 i ,. ;.? ch (ch ₅ ) ₂ H H OCH, 3 H H B i. . > CH (CH ₅ ) ₂ H H H OH, 3 CH, 3 B C '·!., -> CH (CH ₂ ) ₂ H H CH, 3 H ch ₅ B { > CH (CH ₂ ) ₂ H CH, 3 H H CH, 3 B ( ') ch (ch ₅ ) ₂ H H H Cl CH, 3 B cm. CH (CH ₂ ) ₂ H Cl H H ch ₅ B c », 3 0H (0Hj) ₂ H H Cl H ch ₅ • B CM, '? CH (CH ₂ ) ₂ H Cl H H och ₅ B -

-75-:

TABLE I «(continued)

/.1 X L M «M Q h. procedure % ·, C, H _n H H H H H A ^{; ;} 3 ° 2 ^H 5 H H H H H A 2- ^C 4 ^H 9 H H H H H A ; £ - ° 4 ^H 9 H H H H H A ^j and Wg H H H H H A ^c; > iC _{Z [} H ₉ H H H H H A cyclopropyl H H H H H A . ch ₂ ch-ch ₂ H H H H H A cyclohexyl / J H H H H H A (ch ₂ ) ₅ H H H H H A 01!., CH (CH ₅ ) ₂ Cl H H H H j 0H (0H ₃ ) ₂ CH- P H H H H and CH (CH ₅ ) ₂ F H H H H CN., CH (CH ₅ ) ₂ och ₅ H H H H ch _} ch (ch ₃ ) ₂ OH H H H H ci> ₃ ch (ch ₅ ) ₂ H H Cl H A

202,5-203,

EXAMPLE

Acid addition salts derived from Old quinolinecarboxylic acids:

Preparation of hydrochloric acid addition salt from methyl-2 (5 “isopropyl-5-methyl-4-oxo-2-imidazolin-2-yl) -3-quinoline carboxylic acid

The solution of the ester is dissolved in a mixture of ether and methylene chloride and cheese. s <with hydrogen chloride; the solution is washed and the precipitate is washed ctro '?. and are · Si in vacuum; m.t · equals 226-27θ ° 0 · The following salts may be obtained: by analogy, if appropriate EX is used, some salts are hygroscopic oils (ethyl acetate is used as the preferred solvent in these reactions)

-i -¾ T ' A L M Q H acid CII, 5 CH (CH ₂ ) ₂ 0 COgCHj H H H H HCl CH, 2 ch (ch ₃ ) ₂ s co ₂ ch ₅ H H H H HCl OH, 3 CH (CH ₅ ) ₂ 0 CO ₂ CH ₅ H H H H HBr CII ₅ CH (CH ₅ ) ₂ 0 CO ₂ CH ₅ H H H H hno ₅ CLI, 5 CH (CH ₂ ) ₂ 0 C0 ₂ CHj H H. H H h ₂ s ° ₄ CII, 5 0H (CH ₂ ) ₂ 0 0 ₀₂ h H H H H HCl 266-27C CII, 5 ch (ch ₅ ) ₂ 0 CHO H H H H HCl CJ.I, 5 CH (CH ₂ ) ₂ 0 ch ₂ oh H H H H HCl CII, 3 CH (CH ₂ ) ₂ 0 co ₂ c ^h 5 H H Cl H HCl CII, 3 CH (CH ₂ ) ₂ 0 CO ₂ CH ₅ H H CH, 3 H HCl CH, 3 ch (ch ₅ ) ₂ 0 COgCHj H ch ₅ H H HCl

EXAMPLE ^ ^{12 ly}

Preparation of 2- (5-Isopropyl-5-methyl-4-oxo-2-yl) -fizo3.in-2-yl) -5binolinecarboxylic acid sodium salt

A solution of 2- (5 "isopropyl-5-niethyl-4-oxo-2-imidazolin-2-yl) 3-quinolinecarboxylic acid (2.35 6, 0.0075 mol) in water (22 cm ^) containing sodium hydroxide (0.3 g, 0.0075 moles) was stirred at room temperature overnight and then washed with methylene chloride; the aqueous layer was separated and concentrated to an orange-colored material, which was washed with ether and air-dried. The product is a dihydrate which is obtained as a cream-like substance, m.p. 235-250 ° C (decomposition).

Analysis calculated for N ^ O ^ Na 2 ^ 0:

C, 55.27; H, 535; N, 11.37; At, 6.22.

Found: C, 55.56; H, 5.51 N, 11.35; At, 6.30.

«> ^W ! ,

Substituting sodium hydroxide with other compounds, salts were similarly obtained. The compounds thus obtained are described in Table VI.

-77-:

TABLE VI \ /

5 Rg X L M «M Q 'd. 0H (0H,) ₂ oh (oh ₅ ) ₂ H H H H ^<:, s CH (CH,) ₂ H H H H C H, > ch (ch ₃ ) ₂ H H H H % ch (ch ₅ ) ₂ H H H H (JI. 0 CH (CH ₂ ) ₂ H H H H ^{(;, 1} 5 ch (ch ₃ ) ₂ H H H H CH. 5 ch (ch ₃ ) ₂ H H H H C H, 5 OH (CH ₃ ) ₂  H H H H Cl! .. 3 ch (ch ₃ ) ₂ H H H H OH. 5 CH (OH ₃ ) ₂ H H H H ^tu i ch (ch ₃ ) ₂ H H H H ulcer 9 ch (ch ₃ ) ₂ H H H H OH, 5 ch (oh ₃ ) ₂ H H H H ^c .v oh (oh ₃ ) ₂ H H H H UH. 5 ch (ch ₃ ) ₂ H H H Cl OH, 3 oh (oh ₃ ) ₂ H H H CH ₃ CH, 5 H H H H (ch ₂ ) ₅ H H H H

ΪΖ M * mp ° C H On 235-250 K H 128-137 H h ₅ nch ₅ H _Η2 Ν ( ^σΗ 3) ₂ H hn (ch ₃ ) ₃ H H ₂ N (C _? H ₇ -i) ₂ 257-259 H NH ₃ CH ₂ CH-CH ₂ H NHjCHgC CH H kh ₃ o ₆ h ₅ H kh ₃ c ₈ h ₁₇ H ^ 18¼ H NH ₅ C ₃ H _? -i 0 H NH ₃ -CH ₂ -i Γ Ίι H Ca ! il H Ca H NH ₂ (C, H ₇ -i) ₂ H ^ 3 ^ 8 ^ 17 H

-78 '

EXAMPLE 'ablation of 2-isopropyl-2-methyl-5S, -imidazo [1 *, 2 *: 1,2 J-pyrazolo / 3,3 b / quinoline 3 (2b [), 5-dione, 2-isopropyl -2-methyl

PROCEDURE A

Dicyclohexylcarbodiimide (3.47 g, 0.0168 aol) in methylene chloride, under a nitrogen atmosphere, was added to a suspension that was potent and contained 2- (5-isopropyl-5-phenlethyl-4-oxo-2-ynidazoline-2 -il) ··

3-quinolinecarboxylic acid: (5.24 g, 0.0168 mol); methylene chloride was used as the solvent and the reaction mixture was stirred at room temperature overnight. After the reaction was incomplete, a further 0.3 g of dicyclohekuyl carbodiimide was added and the mixture was stirred for a further 48 hours. The reaction mixture was evaporated and the yellow substance purified by chromatography on silica gel. The product was eluted with acetonitrile-and methylene chloride as a white substance, which crystallized from toluene, m.p. Mp 225-227 ° C.

Analysis calculated for C, 69.61; H, 5.15; N, Found: 0, 69,? 6; H, ° 17 ^H 15 ^N 5 ° 2 ^!

14,33.

5.31; N, 14.13.

-79 ·

EXAMPLE 14

PROCEDURE B

Preparation of cia and trans 1,1b-dihydro-11b-hydroxy-3-isopropyl, 3-methyl-5-H-imidazofin-1 ', 2': 1,2,2-pyrrolo-3,4-bJ quinoline ·

A solution of 10-dihydro- [C-isopropyl-tZ-methyl-1,3-dioxo-2-ylpyrrolo [3,4-b] Zbinolin-2-acetamide (00 g »0.0016 mol) in xylene was heated at reflux temperature 23 auto. The cold substance is precipitated white substance in an amount of 0.17 g, t, t. 191-192 [deg.] C. and subsequently 0.1 g of a m.p. 187-189 ° C when the filtrate is diluted with hexane.

Analysis calculated for.C ^^ H ^^ N ^ O ^: 0/6508; H, 500; N, 1300. Found: C, 66.08, H, 5.65; N, 13.00.

Other triocyclic products were synthesized by similar assays A and B described herein.

-Examples of tricyclic products

^L X 0 0 M <J t Q-CH ₅ ΥΫ_ώ < ' ^R 1 s ₂ <IT ^R ? -Χ, Ι, Μ, Η- «H «Χ-OHj R ₂ -CH (OH ₅ ) ₂ Q «C1 X, i, m, r ₇ H ^B l ' ^CH 3 R ₂ rOH (CH ₅ ) ₂ M «CH, 2 x, M, r ₇ -H R ^ -GH ^ R ₂ -CH (CH ₅ ) ₂ M-01 x, L, q, s ₇ -H Rj-CHj R ₂ -CH (CH ₅ ) ₂ qc? ₅ X _t L, M, R ₇ -H Βχ-OHj R ₂ -CH (OH ₅ ) ₂ MH (CH3) ₂ χ, Μ »^ -H Εχ-ΟΗ, R ₂ «CH (CH ₅ ) ₂ M-OCHj x, l, q, r ₇ -H R ^ CHj . R ₂ * CH (CH ₅ ) ₂ Χ-ΟΗ x, l, q, r ₇ -H ΟΗ _χ «ΟΗ ₅ R ₂ «CH (CH ₅ ) ₂ X, L, M, R, Q- H Kj r ₂ ch ₅ 0 ^ ch ₅ ° 5 ^H 7 ch ₅ θ4 ^Η 9 n • oh ₅ ^G 4 ^H 9 ' nek • CHj ^G 4 ^H 9 ' • iso ch ₅ Δ (ch ₂ ) ₅ - ch ₅ o

-8Ί EXAMPLE 15

Purification of 5 N -isopropyl-5-methyl-2- (2-quinolyl) -2-imidazolium- ^; ii) iia. *

^0H 5

CONH - ^ - OOBHg

CH (CH ₂ ) ₂

HHό / ^0H ?

OHCCIlj),

The slurry of N- (1-carbamoyl-1,2-dimethylpropyl) -2-quinolinecarbocoamide (16.04 g, 0.0562 mol) in xylene (610 cm &lt; + &gt;), in a nitrogen atmosphere, added 50% of an oil dispersion of sodium hydride ( 2,? G, 0.0562 moles) at 20 ° C. The reaction was refluxed for 2 hours, cooled and water (50 cm &lt; ^{9 &gt;} ) added. The aqueous aloe was extracted with methylene chloride and the organic layers were combined and evaporated to give a yellow oil (17 g). A pale yellow substance was obtained which crystallized from ethyl acetate to give 11.77 β (78%) of a white substance, mp 112-117 ° 0.

Analysis calculated for ^C 16 ^H l ₇ ^N 3 ^Oi

C, 71.88; H, 6.41; N, 15.72.

Found: 0, 71.91; H, 6.47} N, 15.70.

Other compounds synthesized in a similar manner are shown in Table IX.

R2 X L M Q · - - - • MM CH _? CH (CH ₂ ) ₂ . OCH, H H H H CH ^ CH (CH ₂ ) ₂ ch ₅ H H H H CH, ? CH (CH ₂ ) ₂ Cl H H H H CH, 5 CH (CH ₂ ) ₂ H H H H Cl CH, 5 CH (CH ₂ ) ₂ H H H H NOg CH, ^C 2 ^H 5 H H H H H CH ₂ ^C 3 ^H 7 H H H H H CH, ° ₄ V » H H H H H ch ₅ ^C 4 ^H 9i H H H H H ch ₅ Ο ^ Ηθ-aek H H H H H CH, 2 H ' H H H H CH, 5 oiclopropyl H H H H H CH _? CH ₂ CH-CH ₂ H H H H • H CH, 5 cyclohexyl H H H H H (0¾½ H H H H H

v *

Claims (1)

1. A process for obtaining new pyridine ^ i. quinoline compounds of the formula: in which A is COOR ^ and R ^ is. hydrogen, alkyl optionally substituted by a C ₁ -C ₂ alkoxy, phenyl, furyl, raethoxyphenyl, hydroxy, halogenphenyl, C ₁ -C ₄ alkylphenyl, nitrophenyl, carboxy, ^C 1 ^C 2 ^a alkoxycarbonyl or C 1 -C 2 trialkylammonium group, ^C 2 ~ C ^ alkenyl, advantageously substituted with hydroxy, C ^ -C ^ alkoxy, phenyl, halogen or C ^ -C ₂ alkoxycarbonyl grupom, C ^ -C ^ cycloalkyl advantageously substituted jednom or two methyl groups, _alkynyl substituted jednom or two a methyl group or a cation selected from the group consisting of alkali metals such as K and Na, alkaline earths such as Ca, ammonium, and H ₂ N (C 1-6) ₂ , R, _J is C 1-4 alkyl. R ₂ is alkyl or cyclopropyl and when R ₂ and R ₂ taken together can represent C 1 -C 4 cycloalkyl optionally substituted by methyl, X is hydrogen, halogen, hydroxy or methyl, W is 0, Y and Z individually represent members selected from the group consisting of hydrogen, halogen, methoxy, methylamine, wherein the compound of the formula is cyclized using PCI,., or a mixture of PCI, - and POCl. in toluene, at room temperature to 100 ° C, whereby the compound may be formed in situ.