DE2355084A1 - COMPOUNDS HAVING A GASTIC ACID SECRETION-INHIBITING EFFECT AND PROCESS FOR THEIR PRODUCTION - Google Patents

Description

Andrejewski, Honke & Gesthuysen patent attorneys Physicist Dr. Walter Andrejewski Graduate engineer Dr.-lng. Manfred Honke

,. _. Graduate engineer

Attorney's file: 42 8lo / W-ma _Hans p _ieter Gesthuysen

4300 Essen, Jl. Oct. 1975 Theaterplatz 3

Patent application

Laboratorio Guidotti & C. S.p.A, Pisa (Italy), Via Trieste 4o

Compounds with gastric acid secretion inhibiting effect and methods of making them

The present invention relates to some 5-substituted ones 6-phenantridone derivatives which have been shown to be useful therapeutic agents as they are a pronounced Have an inhibitory effect on gastric acid secretion and therefore special are useful against peptic ulcer and hyperacidity. -

The compounds of the present invention are as follows general formula

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) n - COQH

where R '= H for η = 0 and R * = H or CH ₃ for η = 1. The scope of protection also includes the salts of the acids mentioned with therapeutically acceptable, for example, alkaline cations,

The preparation of the new compounds is shown in schemes I - VII of the accompanying drawing, with the various Manufacturing process each with the letters. A to G are designated.

Procedure A (Scheme I) consists in

a) that 2-amino-biphenyl- ² f-carboxylates or -4-methyl acetates (III) are acetylated, the corresponding acetyl derivatives (IV) being obtained,

b) that the acetyl derivatives (IV) _{are treated with POCl 5} in order to obtain the 6-methylphenantridine-3-carboxylate or -3-methyl acetate (V),

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c) that the latter in their corresponding acids (Vl) are hydrolyzed, which by oxidation to the corresponding 6-phenantridone-3-carboxyl or -J-acetic acids (VIII) are converted, or alternatively to the aforementioned stage c),

d) that the 6-methyl-phenantridine-j5-carboxylate or the -3-methylacetate (V) into the corresponding 6-phenantridone ester (VII) are oxidized, which, as an alternative, the corresponding acids (VIII) and by means of hydrolysis by alkylation with CH ^ J the 5-methyl-6-phenantridone-

■ 3-carboxylate or -I-methyl acetate. (XXVIII) and with the following Hydrolysis of the N-methyl-ö-phenantridone - ^ - carboxylic acids or acetyl acids (XXIX).

Process B (scheme II) provides for the application of the Schmidt reaction with sodium azide and sulfuric acid to tertiary amides of the 9-fluorenone-2-carboxyl or -2-acetic acids (X) which have been prepared from the corresponding acids (IX), for the purpose of obtaining the phenantridonic acids (VIII) via the corresponding phenantridone amido derivative (Xl). The latter can be prepared starting from the 9-5 ^l luorenone-2-carboxyl or -2-acetic acid (IX) via the corresponding oxyme (XII) and treating the latter with polyphosphoric acid.

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Scheme III ( process C ) shows the synthesis of 6-methylphenantridine-J5-acetic acid (XVII) and thus 6-phenantridone-3-acetic acid (XVIIl) starting from o-methylphenantridine-J-carboxymethylate (XIII) via reduction with LiAlH ₂ ^ to (XIV), chlorination with PCl ₅ to (XV) and transition to nitrile (XVT); the desired acid (XVII) is obtained from the latter by means of acid hydrolysis.

Process D (scheme IV) provides for the preparation of the 6-phenantridone-; 5-carboxyl- and -J5-acetic acids (VIII) by means of condensation in the presence of AlCl., And subsequent alkaline hydrolysis of the I-ethoxycarbonilamidobiphenyl carboxylate or methyl acetate (XIX), which in turn were obtained by reacting the corresponding amines (III) with ethyl chlorocarbonate.

Process E (scheme V) consists in the treatment according to the experimental conditions, followed by the Arndt-Eistert reaction of the diazoketone shown in formula (XXII), obtained by reaction with diazomethane of the chloride of 6-phenantridone-3-carboxylic acid (XXI) for the purpose of obtaining 6-phenantridon-j5-acetic acid (XVIIl).

In process F (scheme VI), the 3-aminobenzoic or 3-aminophenylacetic acid (XXIII) is reacted with the chloride of the o-nitrobenzoic acid so that the corresponding

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2-nitrobenzoamides (XXIV) result, which then catalytically are reduced to the amines (XXV); these 'result in the latter by diazotization and decomposition of the diazone salts with Cu one Mixture of the two products (VIII) and (VIIIa), which means fractional crystallization can be separated.

Method Q (Scheme VII) represents the same method of reduction, diazotation and decomposition with Cu on ^ -nitro-J-benzoilamidobenzoic acids or phenylacetic acids (XXVII); benzoilization gives amino azides (XXVI); in this case the acids (VIII) are obtained as end products.

The above procedures are illustrated by the following examples explained in more detail:

Method A (scheme I) 2-acetamido ^ biphenyl-4-methylcarboxylate (IV with η = - 0)

A mixture of 2.27 g of 2-amino-biphenyl-4-methylcarboxylate (Hl) and 2 ml of acetic anhydride is at room temperature Stirred for 5 hours. It is poured into water; the recorded solid component is crystallized from ethanol-water. Yield 2.4 g; Melting point 129.5-130 ° C.

6r-methyl-phenantridine - $ - methylcarbo: xylate (V * with η = l).

2.35 g of 2-acetarmido-biphenyl- ⁱ ^ -methylcarboxylate (IV) are dissolved in 6 ml of POC1-; the solution is stirred and on

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Heated llo ° - 115 ° C for two hours, during which a violent formation of gaseous HCl occurs. The excess of POCl is removed in vacuo; the remainder is taken up with 50 ml of ground ice; the solution is neutralized with 5% NaHCCLz; the crystalline precipitate is collected, washed with NaHC (X diluted to 5% ) and crystallized from ethanol to a melting point of 155 ° C. Yield: 9-4 % of theory.

6-methyl-phenantridine-3-carboxylic acid (VI with η = 0)

A mixture of 1 g of (V) in 15 ml of Io ^ -igem ethanol-KOH is refluxed with stirring for 3 hours. Of the Resin precipitate is separated off, dissolved in water and acidified with acetic acid. The precipitate is absorbed and crystallized from ethanol. Melting point 295 ° - 297 ° C (with decomposition).

Oxidation of o-methyl-phenantridine-jS-carboxylic acid (VI) with KpCr ₂ O ₇ : 6-phenantridone-3-carboxylic acid (VIII with η = 0) (XX)

_{6.6 g of KgCr 2} O _{7 are} added to a solution of j5 g of methylphenantridine-3-carboxylic acid (VI) in 45 ml of glacial acetic acid, heated to 100 ° and stirred; the solution is then held at 12o C for 4 hours. It is mixed with 12o ml of dilute HCl (1: 1)

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taken up and the solid stock obtained by treatment with 5 % dilute NaHCO, cleaned and precipitated with dilute HCl. Crystallized from dioxane, it melts at 33o ° C.

Oxidation of o-methylphenantridine - ^ - methylcarboxylate (V) with CrO - z: 6-phenantridone-methylo'arboxylate (VII with η = 0).

A solution of 5 g of δ-methyl phenantridine - ^ - methyl carboxylate (V) and 50 ml of glacial acetic acid, heated to 100 ° C, are in 8o Minutes Io g of CrO, added. It is heated to 120 ° C for 1 hour heated and poured into 4oo ml of water; the solid precipitate is separated, several times on a filter with warm water washed and crystallized from dioxane. Melting point: 227-228 ° C.

Hydrolysis of 6-phenantridone n-3-carboxylmethylate (VIl): 6-phenantridone-3-carboxylic acid (VIII with η = 0 ) (XX)

A slurry of 1 g of the ester (VII) in 35 ml of aqueous KOH to 10% is heated under reflux for 2 hours. The undissolved part is extracted by filtration; the filtrate is acidified with concentrated HCl; the colloidal precipitate is collected and purified according to known methods to give 0.350 g of o-phenantridone ^ -carboxylic acid (VIII).

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2-acetamido-biphenyl-4-methyl acetate (IV with η = 1)

23.3o g (0.965 mol) 2-aralno-biphenyl-4-methyl acetate (III) 15 * 30 g of acetic anhydride are added dropwise. The mass is poured into ice water, filtered and the residue is dried. Melting point: 12o ° - 121 C.

6-methyl-phenantridine-3-methyl acetate (V with η = 1)

A mixture of 25.75 g (0.0909 mol) of 2-acetamido-biphenyl-4-methyl acetate (IV) and 71 ml of POCl is heated to Ho-120 ° C. for 2 hours. The excess POCL is distilled, the remainder is taken up with 350 ml of ice and the resulting slurry is neutralized with NaHCO-. The precipitate is collected crystallized _r dried and crystallized from ligroin. Melting point: 94 ° - 95 ⁰ C.

6-methyl-phenantridine-3-acetic acid (VI with η = l)

A mixture of 1 g of 6-methyl-phenantridine-3-methyl acetate (V) in 15 ml of 2o # alcoholic KOH is im Leave to reflux. After evaporation, dissolution of the residue in water and acidification with glacial acetic acid, 0.8 g of one are obtained Product obtained which melts at 188-189C.

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o-Phenantridon- ^ methyl acetate (VtI with η = 1)

One. Solution of 5.3o g (0.02 mol) of 6-methylphenantridine-j5-methyl acetate (V) in 5o ml of glacial acetic acid at loo ° C in small Log CrCU servings added and then for another hour heated. It is poured into 750 ml of water, filtered and washed repeatedly on a filter with hot water. Of the The rest is with dioxane and then with ethanol crystallized to a melting point of 210-211 ° G.

6-phenantridone-acetic acid (VIII with η -. L) (XVIIl)

A mixture of 1.14 g of o-phenantridone-I-methyl acetate (VIl) in 20 ml of Io # -iger ethanolic KOH is refluxed for 2.5 hours. It is evaporated to dryness, absorbed with HgO, filtered and the filtrate is acidified with concentrated HCl. The precipitate is collected, washed several times on a filter with water and bisected by solution in aqueous dilute Na ₂ CO-Z and repeated precipitation with HCl

₂
purified 272 ⁰ C - to a constant melting point of 271 °.

5 "methyl-6-phenantridon-3-methyicarboxylate (XVII with η = θ)

A solution of 0.9 g (0.023 mol) of NaNH ₂ and 5.85 g (0.025 mol) of δ-phenantridone-jJ-methylcarboxylate (VII) in 30 ml of hexamene tapol (HMPT) is stirred for 6 hours heated to 75 ° C for a long time until

Andrejewski, Honke & Gesthuysen, patent attorneys; 4300 Essen 1, Theaterplatz

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the ammonia development ceases. After addition of 1.5 ml of methyl iodide is stirred at room temperature for 4 hours ^, o again, added 5 ml of methyl iodide and heated for one hour on Jo C. The whole is poured into ice, leaving a solid, violet-colored residue, which is collected and washed several times with water in a mortar. After drying, it melts at 1–4–182 ° C. He is from a small amount of ethanol and dioxane to constant melting point of l84 ° - 185 ⁰ C crystallized. Yield: 65 % of theory.

S-methyl-e-phenantridone - ^ - carboxylic acid (XXIX with η = 0)

A mixture of 3 * 2 g of S-methyl-o-phenantridone - ^ - methyl barcoxylate (XXVIII with η = 0) in 60 ml of Io # -iger ethanolic KOH is refluxed for 3 hours. It is filtered, the residue dissolved in water and the solution acidified with glacial acetic acid. The precipitate is collected by filtration, it is dried and extracted in Sohxlet with ethanol for 10 hours. By concentrating the ethanol solution and cooling, a crystalline precipitate is deposited (2.1 g), which is further purified by crystallization from a little dioxane. Melting point: 298 ^° C. (with sublimation).

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Method B (Scheme II)

Schmidt reaction to 9-fluorenone-2-earboxypyrrolidin (X); 6-phenantridone-3-carboxypyrrolidine (XI)

A flood of 2.9 ° g (0.05 mol) of sodium azide in 20 ml of chloroform, cooled with ice, 9.5 ml of conc. HpSOh added. When the temperature has risen again to 25 ° C, 8.45 g (0.05 mol) of 9-fluorenone-2-carboxylpyrrolidine (X) are gradually added in small amounts to control the flow of nitrogen. Stir for one hour at room temperature, dilute with water and stir for 2 hours. The yellow resinous precipitate is taken out, washed with water and dried. A sample is applied to a thin layer (eluent:] detector chloroform: UV light) chromatographed and proves to consist of only one component, with insignificant trace impurities, is purified by crystallization from ethanol "melting point 236 ^{0-237 0} Cj yield 72nd %.

Hydrolysis of 6-phenantridone-3-carboxy pyrrolidine (Xl); 6-phenantridone-3-carboxylic acid (VIII with η = 0) (XX)

A mixture of Ig pyrrolidine (Xl) in 3o ml of conc. HCl is refluxed for 2 hours. It is filtered and the residue is dissolved in dilute Na ₂ CO- * and precipitated by means of acidification. The product obtained is purified by crystallization from dioxane and identified as 6-phenantridone-3-carboxylic acid (XX) by means of the melting point in the mixture, IR spectrum and elemental analysis.

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Modification of procedure B: 9-fluorenone-2-carboxyl-oxymic acid (XII)

50 g fluorenone-2-carboxylic acid (IX with η = 0) and 50 g NaHC (X are dissolved in 750 ml 50 # EtOH; the solution is _{treated with stirring in small amounts with 25 g NH 2} OH, HOL and the The solution is heated under reflux for 2 hours. Cooling gives a yellow, crystalline precipitate which is collected. Melting point 284 ° C., yield 75% .

o-phenantridone-jS-carboxylic acid (XX)

10 g of 9-fluorenone-2-carboxyl-oxym (XII) and 20 g of polyphosphoric acid are poured into a necked flask with a cooling device and mechanical stirrer. The mixture is stirred vigorously and heated to 160 ° C. for 10 minutes. The hot mixture is poured into ice water; the residue is collected by filtration, dried and analyzed. Yield 81 %.

Similarly, starting from 9-pluorenone-2-acetic acid (IX with η = l) the 6-phenantridone-3-acetic acid obtained (VIII with η = l) (XVIII).

Method C (Scheme III) 3-Hydroxy-methyl-6-methyl-phenantridine (XIV)

A solution of 2.51 g (o, ol mol) ^ -carboxy-methyl-ö-methylphenantridines (XIII) in 6o ral tetrahydrofuran are 0.38 g

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(ο, oil mole) LiAlH ^ added at room temperature with vigorous stirring for 1/2 hour. After stirring for a further 1/2 hour, 5 ml of HgO are added and the flood is adjusted to a pH of 7 using HgS (XN / 2. An organic layer is prepared (using salts with NaCl), which can be diluted considerably with HgO A product in the form of a needle crystal can precipitate, which is collected on a filter, washed with HgO and dried on PgOp-, crystallized out from CCl ₂ , with a melting point of 119 ° -12o ° C.

3 ~ chloro-methyl-3-methyl-phenahtridine (XV)

1.21 g (0.05 mol) of 3-hydroxymethyl-6-methyl-phenantridine (XIV) are added to 3 ml (0.04 mol) of SOCIg. The reaction is exothermic. It is refluxed for 1 hour and evaporated to dryness in vacuo to give 1.7 g of a solid yellowish product. It crystallizes from chloroform. Melting point: 178 ⁰ - L8L ° C.

^ -Cyaninethyl-e-methyl-phenantridine (XVI)

0.80 g (0.17 mol) of NaGN in 10 ml of dimethyl sulfoxide is added to a solution of 2.40 g (0. oil mol) of ^ -chloromethyl-o-methyl-phenantridiri (XVl) in 20 ml of dimethyl sulfoxide. The Reaktionsmischühg is 2 hours Läng heated at 80 ^0C. The nitrile will

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isolated by pouring the whole into HpO and collecting the deposited solid product on a filter. It crystallizes from ethanol using vegetable charcoal. Melting point: 137 ° - 139 ⁹ C.

o-Methyl-phenantridine - ^ - acetic acid (XVII) .

The hydrolysis of 1.16 g (0.05 mol) of 3-cyano-methyl-6-phenantridine (XVI) is carried out with 0.78 g (0.05 mol) in hydro-alkaline solution (3 ml HpO and 12 ethanol) under reflux of the reaction mixture for 4 hours. Isolation is carried out by evaporating the ethanol in vacuo by diluting with plenty of H ₂ O and neutralizing with dilute acetic acid. The solid product that separates out is collected. It crystallizes from isobutanol.

6-phenantridone-3-acetic acid (XVIIl)

The oxidation of 6-methyl-phenantridine-3-acetic acid (ΐ, βο g) (XVII) is carried out by adding 3.2o g of potassium dichromate to a vinegar solution (11 cnr). The addition takes place at 100 ° C. with stirring. The mixture is heated for 4 hours at 12o ° C and the product obtained is isolated by the Raktionsmischung in 60 cnr HCl 1: 1, at 6o ° - ⁰ .70 C is heated poured, and the precipitated product is collected on a filter. It is cleaned by means of alkaline dissolution and subsequent acidification.

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Method D (Scheme IV) 2-Ä * thoxycarbonilamido-biphenyl-4-methyl acetate (XIX with n-l)

A flood of 8.75 g (0.0564 mol) of 2-amirtobiphenylmethyl acetate (III with η = I) in 50 ml of acetone in the presence of lo.7o g (0.075 mol) of anhydrous KgCO., Are added dropwise to about 30 minutes with stirring and cooling with water 4, 10 g (0.038 mol) of ethyl chlorocarbonate was added. The mixture is stirred at room temperature for a further 2 hours, then filtered to remove the crystalline precipitate and the piltrate is evaporated in vacuo. The oil residue is fractionated and gives lo.9o g (yield 96 %) of urethane (XIX with η - l). Boiling point I70 ⁰ - mm 173 ⁰ C at 0.05.

6-phenantridone-3-acetic acid (XVIII)

A solution of 7 * 88 g of 2-A * thoxycarbonlamido-biphenyl-4-methyl acetate (XIX with η = m) is added to a flood of 4 g of AlCl. * In 15 ml of o-dichlorobenzene; the mixture is ^{heated to 190 °} C. for 2 hours and the solvent is then evaporated off in vacuo. The residue is treated with 25 toi 15% diluted HCl; the resinous product formed in this way and obtained by precipitation is heated under reflux for> hours with 50 ml of ethanol-KOH. The solvent is evaporated; the residue is dissolved in water and the

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Solution filtered and acidified; the precipitate is collected and further purified by dissolving in NaHCO- ,, filtration and acidification. The product obtained is treated with pure boiling ethanol, filtered and dried. Melting point 273 ° - 275 ⁰ C.

Method E (Scheme V)

Preparation of 6-Ph, enantridon-3-acetic acid) XVIIl) starting from 6-phenantridone-3-carboxylic acid (XX)

5.14 g (o, o2 mol) of 6-phenantridone-3-carboxylic acid (XX) chloride (prepared by heating under reflux of 4.78 g (o, o2 mol) of 6-phenantridone-3-carboxylic acid (XX) with 13 ml of thyonil chloride and with evaporation to dryness) in 2oo ml of dioxane are added to a benzene solution of diazomethane, which is cooled with acetic acid and shaken vigorously, which solution of J> 6 g of Ni tros ome thyl urine t off (o, 35 Mol), Ho ml of aqueous 45% KOH and J> 60 ml of benzene. After the addition is complete, stirring is continued for a further 6 hours at room temperature and then left to stand overnight. The crystalline precipitate collected by filtration is straw yellow and has bands corresponding to the structure of the diazoketone (XXII) in the IR spectrum. This precipitate (4.2o g) is suspended in 150 ml of methanol; the flood is heated to reflux and, with vigorous stirring,

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treated at regular intervals of 1 hour with 5 servings of 500 mg freshly prepared Ag ^ O; after the additions have ended, the mixture is heated and stirred for a total of 5 to 9 hours. It is diluted with 150 ml of methanol, heated to a boil and filtered; by evaporation of the filtrate to dryness, 3 > 60 g of o-phenantridone - ^ - methyl acetate (VII with η = 1) are obtained, which by means of alkaline hydrolysis (as described in process A: transition from compound VIII to compound XVIII) 2 , Io g of 6-phenantridone-3-acetic acid (XVIII) gives a yield of 41.5 % compared to the starting acid (XX). .

Process ff (scheme VI) 3- (o-nitrobenzamido) benzoic acid (xxiv. With η = 0)

Io g of m-aminobenzoic acid (XXIII with η = 0) in 100 ml of aqueous NaOH 2N are treated with a solution of o-nitrobenzoil chloride (prepared from 12.3 g of o-nitrobenzoic acid) in 50 ml of ether, which is contained in small portions and with vigorous stirring. Finally, the aqueous alkaline layer is separated, acidified cold with dilute HCl and the crystalline precipitate collected by filtration. Yield: 1.5 g of (XXIV with η = 0), after crystallization Ethanol. Melting point 2β2 ° - 264 ⁰ C.

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Reduction of 3- (o-nitrobenzamido) benzoic acid (XXiV with η = θ) Diazotation and decomposition (cleavage) of the diazonium salt: e-phenantridone-Q-carboxylic acid (XX)

7 g of 3- (o-nitrobenzamido) benzoic acid (XXIV with η = θ) in ethyl acetate (Jo ml) - and a slurry of 8 g of Ni-Roney in the same solvent (Io ml) are combined and in the presence of hydrogen Ms for complete absorption of the theoretical amount 'stirred. Removal of the catalyst by filtration and the solvent by evaporation in vacuo give an oily residue which hardens by treatment with petroleum ether (eg at 60 ° -80 ° C.). This gives 5 g of a product which cannot be recrystallized, but gives a red color as a result of diazotization and copulation with alkaline β- naphthol. 5 g of the crude amine (XXV) are diazotized in a mixture of concentrated HCl (J ml) and water (30 ml) with sodium nitrate (3 * 5 g) in water (15 ml). The flood obtained is filtered to separate out 1 g of substance which has remained undissolved (3- (o-nitrobenzamido) benzoic acid (XXIV)) and the filtrate is diluted with water (35o ml) and treated with urea (3 g) . 4 g of powdered Cu are added to the solution; the slurry is stirred at room temperature for 48 hours. It is treated with aqueous NaOH until a distinctly alkaline reaction is obtained, filtered and acidified; it turns out a brown substance, polygamy

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turns out to be a mixture of ö-phenantrid-lon-J-carboxylic acid (XIII with η = θ) and 6-phenantridone-1-carboxylic acid (Villa with η = 0) proved to exist; this mixture was repeated by means of Crystallizations from glacial acetic acid, separated until 1.28 g of δ-phenantridone-O-carboxylic acid (VIII with η = 0) are obtained. Using a similar procedure, starting from 2-aminophenyl-acetic acid (XXIII with η = 1), 6-phenantridone-3-acetic acid was obtained (XVIII) obtained.

Method G (Scheme VII) 4-Nitro-3-benzamido-benzoic acid (XXVII with η = 0.)

18.2 g (0.1 mol) of 3-amino-4-nitrobenzoic acid (XXVI) are dissolved in loo ml of 10% aqueous NaCH and the solution in small portions, stirring vigorously, 14 g (o, l mol) Benzoi chloride added. At the end it is at room temperature Stirred for 2 hours, then acidify the solution using dilute HCl; the crystalline precipitate is collected and dried and raw used for the subsequent reaction.

Reduction of 3-nitro-4-benzamidobenzoic acid (XXVII with η = O) Diazotation and decomposition of the diazone salt: 6-phenantridone-3-carboxylic acid (VII with η = 0) (XX)

9g of 4-nitro-4-benzamidobenzoic acid (XXVII with η = 0) dissolved together with 6 g of Ni-Raney in 6o ml of ethyl acetate, the Flood becomes in the presence of hydrogen until it is absorbed

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the theoretical amount stirred. The catalyst is removed and the solution evaporated to dryness. The resinous residue is concentrated with 7 ml. HCl and J> o ml of water were taken up, the flood was filtered to separate out the undissolved part and the filtrate was diazotized with 3 * 5 g of sodium nitrite in 15 ml of water. It is diluted with 200 ml of water; after treatment with urea (2.5 g), 3.5 g are obtained. Powdered Cu was added and the slurry was stirred for 48 hours at room temperature. After alkalization with aqueous NaOH (Io #) and filtration, the filtrate is acidified with dilute HCl; the 6-phenantridone-3-carboxylic acid (XX) which precipitated is collected by filtration.

With a similar procedure starting with 5-amino-4rnitrophenyl-acetic acid (XXVI with η = 1) became 6-phenantridone-j5-acetic acid (XVTII) obtained.

409820/1156

Claims (1)

Andrejewskir Honke & Gesfhuysen, patent attorneys, 4300 Essen 1, Dwatefpkatz - 21 - Patent claims: 1. Connection with gastric acid secretion inhibitory and against Gastrointestinal ulcer active action, characterized by the Acids of the formula (CH ₂ ) η - COOH in which R '= H for η = 0 and R' = H or CH, for η ~ 1 stands, as well as their salts with therapeutically acceptable cations. 2, compounds according to claim 1, characterized by the Acid of formula ' (CH ₂ ) - COOH and their salts with therapeutically acceptable cations « 409820/1158 Andrejewski, Honk & Gesthciysen, patent attorneys, 4300 Essen 1, "iheoterplati 3 - 22 - j5. Compounds according to claim 1, characterized by Acid of the formula CH ₂ - COOH and their salts with therapeutically acceptable cations. 4. Compounds according to claim 1, characterized by the acid of the formula COOK and their salts with therapeutically acceptable cations. 5. Process for the preparation of the compounds according to a of claims 1 to 4, characterized in, 409820/1158 Andrejewski, Honke & Gesthuyiers, Fatentonwlälte, -4300 Esssn 1, Theoterplcrtz 3 a) that 2-amino-biphenyl ~ 4-carboxylate or -4-methyl acetate acetylated, with the corresponding acetyl derivatives be obtained b) that the acetyl derivatives are treated with POCl to the 6-methylphenantridine-3-carboxylate or -3-methylacetate to obtain, c) that the latter are hydrolyzed to the corresponding acids, which latter by means of oxidation to the corresponding 6-phenantridone-3-carboxyl or -3-acetic acid um- . be converted, or alternatively to this stage c) d) that the 6-methyl-phenantridone-3-carboxylate or -3-methyl acetate are oxidized into the corresponding 6-phenantridone esters, which, as an alternative, hydrolyze the corresponding Acids and by means of alkylation with CH-, J die 5-methyl-6-phenantridone-3-oarboxylate or -3-methyl acetate and with subsequent hydrolysis the N-methyl-6-phenantridone-3-carboxyl- or acetic acid, 6. The method according to claim 5 *, characterized in that that the acids are formed into salts. 409820/1156 Andrejewski, Honke & Gesthuysen, patent attorneys, 4300 Essen 1, Theaterplatz - 2k - 7 · Process for the preparation of the compounds of formula (CH ₂ ) - COOH with η = 0 or 1 according to claim 1, characterized in that that the Schmidt reaction is used with sodium azide and sulfuric acid and thereby of the tertiary amides of 9-E'luorenon-2-carboxylic acid or acetic acid is assumed. 8. The method according to claim ¹ J, characterized in that the 9-fluorenone-2-carboxylic or acetic acid are converted into the corresponding oxymes and these are treated with polyphosphoric acid. 9 · Process for the preparation of 6-phenantridone-3-acetic acid characterized in that the 6-methyl-phenantridine-j5-methyl-carboxylate by means of Li AlH, is reduced to the corresponding alcohol and this is chlorinated, nitrilized and acidic is hydrolyzed. ... 409820/1156 Andrejewski, Honke & Gesthuysen, patent attorneys, 4300 bsseti t, theaterpfäfz 3 10. Process for the preparation of the 6 ~ phenantridone-3 ^ carbö: xyl- or acetic acid, characterized in that it consists of the Condensation with AlCL, the ethoxycarbonilamidobiphenylearboxylate or methyl acetate and the subsequent hydrolysis of the reaction compound. 11. Process for the production of 6-phenantridone-3-acetic acid, characterized in that the chloride of 6-phenantridone-3-carboxylic acid is made to react with diazomethane, and the resulting diazoketone uiiter the Arndt ^ -Eistert reaction conditions is decomposed *; . 12. Process for the preparation of the o-phenantridone-J-carboxyl- or acetic acid, characterized in that the j5-aminobenzoe- or 3-aminopheny! acetic acid with the chloride of o-Nitrobeiizoic acid is made to react that the corresponding Amides are catalytically reduced and the corresponding diazone salts are diazotized and decomposed. 15. Process for the preparation of the ö-phenantridone-J-carboxyl- or acetic acid, - characterized in that the means Benzoilization of 3-amino-4-nitropneny-acetic acid or 35-amino-4-nitropneny-acetic acid obtained ^ -nitro - ^ - berizilamidobenzoic acid- or phenylacetic acid is reduced, diazotized and decomposed with copper » 409820/1156 Empty e f te