DE1670496A1 - 2-oxoindoline-3-carboxylic acids and esters thereof - Google Patents

Description

Center National De La Recherche Scientifique Paris , France

2-oxoindoline-3-carboxylic acids and esters thereof

The invention relates to 2-oxoindoline-3-carboxylic acids and their Ester of the formula

COOH

(D

in which R and R for hydrogen or an unsubstituted or substituted alkyl or aralkyl group or, together with COO and the ring carbon atom 3, for a lactone ring with 5 or 6 elements including the ring oxygen atom, R ² for an OH group or for iie same groups such as R and R ¹ , and X and Y represent hydrogen, halogen or an alkyl or alkoxy group having 1 to 5 carbon atoms, or an aralkoxy, trifluoromethyl, hydroxy, amino or sulfonamido group.

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1 2 The substituents in the alkyl or aralkyl groups R, R and R halogen atoms, free, etherified or esterified hydroxy groups, carboxy and carboxy ester groups, amido, nitrile, Be amino, amine salt or quaternized amino groups

The invention also relates to a process for the preparation of the compounds of the formula I ₀

The inventive method for the preparation of a compound of the formula I, in which R is H or OH, consists in that a 2- (2-nitrophenyl) malonic acid compound of the formula

/ COOR

^ Y * \ / I "» fiflllW V - * "* - /

in which R and R have the meanings given above and X and Y mean the same as X or Y or be an NOp group can be reduced.

The reduction yields 2 - (- 2-hydroxyaminophenyl) malonic acid derivative as an intermediate compound (R »OH), or 2- (2-aminophenyl) malonic acid derivative

(III)

(E ² * OH) the formula Χ - / COOR Υ—- /
• ν I> COOR
R ¹

which is not isolated in most cases, and leads to a cyclic hydroxamic acid (R ² «* OH in formula I) or a lactam (R ² = H in the same formula) with elimination of ROH (water or an alcohol).

If, in compound II, X or Y is either an NO ₂ or an alkoxy group, these can be converted into an amino or a hydroxyl group during the reduction.

Hydrogen in the presence of a hydrogenation catalyst can be used as a reducing agent or a reducing compound can be used which is capable of in neutral, acidic or alkaline To act as a medium. The choice of reducing agent depends on it.

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■ - 3 -

from which connection ^ is to be formed. For example leads the reduction by means of hydrogen in the presence of a hydrogenation catalyst to a compound I in which R is hydrogen, while the reduction by means of an alkali metal borohydride

2 3U leads to a compound I in which R is a hydroxyl group

Among the compounds of the formula II that are used in the synthesis of compounds I are hitherto unknown, new connections.

The invention further comprises a process which consists in treating a 2-oxoindoline-3-carboxylic acid or an ester of the formula

COOR

R ¹

(IV)

in which R, R, X and Y have the meaning given above, are subjected to an alkylation or aralkylation. The hydrogen atom in the 1-position and optionally the Wasserst off atoms which are symbolized by R and / or R are here by an unsubstituted or substituted alkyl or Aralkyl group replaced. Depending on the circumstances, one, two or three alkyl or aralkyl groups can be introduced in this way wecden.

According to another embodiment of the process according to the invention, if R is an alkyl or aralkyl group, R can be exchanged for another R group by transesterification.

In the case of a direct alkylation or aralkylation, a salt of the compound IV and an itarkic base, in particular an alkali metal hydroxide, alcoholate, amide or hydride are reacted with an alkyl or aralkyl halide or ester. If a transesterification is to be carried out, an ester IV with an aliphatic or araliphatic alcohol in Presence of an esterification catalyst, especially a strong one Acid or base.

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The reactions described above can in the absence of a Diluent, in a diluent or in a mixture of diluents which are protonic can be, e.g. in alcohols, or aprotic, e.g. in aromatic. Hydrocarbons, ethers, Ν, Ν-dialkylamides, Sulfoxides and sulfones. The salts of the compound IV to be used can be formed in situ.

The new 2-oxoindoline-3-carboxylic acid compounds of the formula I. are useful as bactericides, analgesics, antispasmodics, anticonvulsants, diuretics, or anti-inflammatory agents, as well as intermediates in the synthesis of other compounds. In particular, they can be used as intermediate products in the production of valuable

W full of 2-oxoindolines can be used by decarboxylation. The following examples illustrate the invention. example 1

Methyl 2-oxoindoline-3-carboxylate

12.6 g (0.05 mol) of dimethyl ester of 2-nitrophenylmalonic acid, dissolved in acetic acid (100 ml), which contains 1 g of 10% palladium carbon, was at room temperature with hydrogen under pressure treated by 50 kg / cm 3o minutes. After the catalyst has filtered off and the solvent was evaporated, the residue became. crystallized by trituration with petroleum ether. After recrystallization 20 ml of methanol gave 8 g ($ 84) of the desired product get pure; M.p. 131 ° 0.

. The starting ester, a new compound which has a melting point of, can be prepared in the same manner as described later for the diethyl ester of 2-methyl-2- (2-nitro-4-trifluomethylphenyl) malonic acid.
Example 2

Ethyl 6-oxy-2-oxoindoline-3-carboxylate

12.4 g (0.04 mole) of ethyl (4-methoxy-2-nitrophenyl) raalonate as it is in C.R.Acad.Sci., series 0,2.6 ^, 84 (1966), has been described in Hydrogenated 100 ml of acetic acid in the presence of 1.2 g of 5% palladium carbon at room temperature under atmospheric pressure. After that theoretical volume of hydrogen had been absorbed, i.e. after 30 minutes the catalyst was filtered off, the solvent evaporated under vacuum and the remaining solid

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recrystallized from 20 ml of methanol. 8.1 g (86 #) of pure compound with a melting point of 110 ° C. were obtained » Example 3

Ethyl i-hydroxy ^ -oxoindoline ^ -oarboxylate

A solution of 5.6 g (0.02 mol) of 2- (2-nitrophenyl) malonate, as described in C. RoAcad.Scio, series 0,26 ^, 84 (1966), in 20 ml of ethanol was under stirred a stream of nitrogen in 10 minutes in a solution of 2.2 g (0.04 mol) of potassium borohydride in 100 ml of water. The mixture was then stirred at ambient temperature for 30 minutes, after which the catalyst was filtered off. The hydroxamic acid was precipitated by acidifying the filtrate with dilute hydrochloric acid; this was recrystallized from 4 ml of methanol; There were three "0 g (68 $ yield) of pure product obtained mi * mp. * 130 ⁰ C.
Examples 4 to 10

Under similar conditions, those in the table below compounds identified by their symbols according to formula I:

example R. R ¹ R ² H X Y M.p. in ⁰ ° C yield H (Recrystalline, H loSÄsmtl.) 7 ° 4th C ₂ H ₅ H H H H 89 (CCl ₄ ) 89 5 C ₂ H ₅ H H 6-Cl H 103 (CCl ₄ ) 82 6th C ₂ H ₅ H H 6-CF ₃ H 139 (benzene) 85 7th C ₂ H ₅ H OH 4-01 H 106 (CCl ₄ ) 57 8th C ₂ H ₅ CH ₃ 6-CF ₃ H 131 (CCl ₄ ) 85 9 C ₂ H ₅ C ₂ H ₅ 6-CF ₃ H 71 (CCl ₄ ) 60 10 C ₂ H ₅ H 4-01 H 107 (CCl ₄ ) 66

The malonic acid diesters used as starting compounds can be prepared as follows for the diethyl ester of 2-methyl-2- (2-nitro-4-trifluoromethylphenyl) malonic acid is described.

To a solution of 52 g (0.3 mol) of diethyl ester of methylmalonic acid 14.4 g (0.3 mol) of 50% strength were obtained in 300 g of dimethylformamide Given sodium hydride under a stream of nitrogen. To the sodium derivative thus formed, a solution became from

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56.5 g (o.25 mole) of 2-nitro-4-Trifluo: nnethylchlorbenzol in 23 g of dimethylformamide was slowly added and the mixture was heated with stirring for 1 1/2 hours at 60 ⁰ C, after which the reaction was completed After _o Distilling off the solvent in vacuo, the residue was acidified with dilute HCl and extracted with ether. The ether was evaporated and the residue was cooled to 0 C, a solid being obtained which was recrystallized from 60 ml of methanol; in this way 58 g (64 $ Ausbette) of the desired product, mp. 44 C ^0.

Similarly, the diethyl ester of of 2-ethyl-2- (2-nitro-4-trifluoromethylphenyl) Malonic acid (mp. 45 ⁰ C) and the dimethyl ester of 2- (2-nitrophenyl) malonic acid (mp. 52 C).
Example 11

Ethyl 4-methoxy-2-oxoindoline-3-carboxylate

10 g (0.032 mol) of 2- (2-methoxy-6-nitrophenyl) malonic acid were hydrogenated at room temperature under a pressure of 50 kg / cm 2 hours in 60 ml of acetic acid in the presence of 0.25 g of 10% palladium-carbon " The catalyst was filtered off, the solvent was evaporated and the residue was crystallized by trituration with petroleum ether. The crude product (714 gi 98 $ yield) was recrystallized from a mixture (io ml) of 2 volumes of methanol and 1 volume of water to give 4.9 g (65 $ Ä.usbeute) of the pure product having a melting point of 130 ⁰ C were obtained.

The starting ester, a new compound, (Söhmp. 60 ⁰ C), was prepared in the manner described below » Examples 12 to 15

The compounds identified below by their symbols according to formula I were prepared in a similar manner:

Example RR ¹ R ² XY m.p. ⁰ C yield

"(Umkr.Lm.) #

12 C ₃ H ₅ HH 5-OCH ₃ H 93 (CCl ₄ ) 80

13 C ₃ H ₅ HH 6-CH ₃ H 130 (MeOH) 72

14 C ₂ H ₅ HH 6-SO ₂ N (CH ₃ J H ₂ 15O (MeOH + H ₂ O) 58

15 C ₂ H ₅ C ₂ H ₅ H 6-NH ₂ H 179 (MeOH) 57

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The starting diesters can be prepared in the same manner as is described below for the diester diethyl 2- (2-methoxy-6-nitrophenyl) malonate, the starting material of Example 11,

To a suspension of 6.7 g (0.27 mol) of 100% sodium hydride in 100 g of hexamethylphosphotriamide (or hexametapol), 42.5 g (0.265 mol) of diethyl malonate were slowly added under a stream of nitrogen. 24.7 g (0.132 mol) of 2-chloro-3-nitroanisole were added to the resulting sodium derivative. 94 ⁰ C), a compound described in JACS ££, 543 (1955), is added dissolved in 65 g hexametapol "The iemisch was then for 30 hours under a nitrogen atmosphere at ⁰ C '90} heated, an analysis revealed that the reaction to about $ 85 was completed, ™

The mixture was cooled, filtered, diluted with 1000 ml of water and acidified with HCl. The separated oil was extracted with ether, the ether layer dried and evaporated. An oily residue was obtained which crystallized. The crystals were allowed to drain off, washed with a mixture of petroleum ether and cyclohexane and recrystallized from 50 ml of methanol. There were obtained • <3 g (44 $ yield) of pure product of melting point 60 C ⁰ * In a similar manner, either in or hexametapol · dimethylformamide diethyl-2-5-methoxy-2-nitrophenylmalonat (mp. 'JO ⁰ O) Diethyl 2- (4-methyl-2-nitrophenyl) malonate (melting point 37 ° C), diethyl 2- (4-N, N-dimethylsulfonamido-2-nitrophenyl) malonate (an oil), diethyl 2- ( 2,6-dinitrophenyl) malonate (mp. 52 ⁰ C) and diethyl-2-i (2,4-dinitrophenyl) -2-äthylmalonat (Schrap. 71 ⁰ C). Example 16

Ethyl 3-methyl-2-oxoindoline-3-carboxylate

The monosodium derivative was formed from 4.1 g (0.02 mol) of ethyl 2-oxoindoline-3-carboxylate and 0.02 mol of sodium ethylate in 30 ml of anhydrous ethanol. To the suspension of this sodium derivative, 50 ml of dioxane was added and ethanol was distilled off; then 3 »2 g (0.022 mol) methyl iodide was added and the mixture was refluxed for 2 hours. Precipitated NaCl was filtered off, the solvent was distilled off in vacuo, and the solid residue was _{recrystallized from CCl 4} (from 10 ml); In this way, 2.8 g (yield: 64%). of the desired 3-methylated compound of mp obtain 85 ⁰ C.

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Ethyl-a-oxoindolin-beta-carboxylate, the starting material, as from diethyl by prepared as follows 2-Nitrophenylmalonsäure (mp _o 45 C), which is obtainable by reacting Natriumäthylmalonat with 2-nitrochlorobenzene in dimethylformamide: 14 g (0.05 Mol) of the diethyl ester were hydrogenated at room temperature under a pressure of 50 kg / cm ^{2 for} 30 minutes in 100 ml of acetic acid which contained 1 g of 10% palladium-on-carbon. The catalyst was filtered off, the solvent was evaporated and the residue was triturated with petroleum ether for crystallization. The crystals were obtained from Cd. recrystallized, whereby 9.1 g (yield: 89 $) of pure ethyl 2-oxoindoline-3-carboxylate, melting point 89 ° C., were obtained.

Example 17 Ethyl 3-benzyl-2-oxoindoline-3-carboxylate

From 4.1 g (0.02 mol) of ethyl 2-oxoindoline-3-carboxylate and 0.02 mol of sodium ethylate in 50 ml of anhydrous ethanol, the monosodium derivative, 4.0 g (0.023 mol) of benzyl bromide, was added to the mixture , and the mixture was stirred at room temperature for 3 hours o sodium bromide was filtered off, the solvent was distilled off in vacuo, the residue was taken up in water and chloroform and the chloroform layer was evaporated to isolate the product formed. «The crude product was _{recrystallized from 60 ml of CCl 4} , and 4, 55 g (77 $ yield) of pure product, mp. 149 ⁰ C were obtained.
Example 18

Ethyl 3- (2-diethylaminoethyl) ^ - oxoindoline ^ -carboxylate and its Picrat

As before, a sodium derivative was prepared from 10.3 g (0.05 mol) of 2-oxoindoline-3-carboxylate in 100 ml of anhydrous ethanol / then the ethanol was replaced with anhydrous dioxane (200 ml). 6.8 g (0.05 mol) of 2-diethylaminochloroethane were added to the mixture, and the whole was ^{heated to 70 °} C. for one hour. Sodium chloride was filtered off, the residue was taken up in anhydrous ether and hydrogen chloride / ethanol was added to the ether solution in order to precipitate the amine hydrochloride. The base, a non-crystallizing oily compound, was liberated by adding potassium carbonate to an aqueous solution of the hydrochloride; it was extracted with ether and its picrate was obtained by the addition

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an ethanol solution of picric acid. After recrystallization from ethanol, the picrate was obtained in a yield of 28 g ($ 53), melting point 145-15O ° C (decomp.)
Example 19

Ethyl -3-benzyl-i- (2-diethylaminoethyl) ^ - oxoindoline ^ -carboxylate From 2.95 g (0.01 mol) ethyl ^ -benzyl ^ -oxoindoline-S-carboxylate, the compound described in Example 17, and 0.01 mol of sodium ethylate, the sodium derivative was prepared in 50 ml of anhydrous ethanol, then 1.5 g (0.011 mol) of 2-diethylaminochloroethane were added to the solution. After standing for 3 hours at room temperature, sodium chloride was filtered off and the solvent was distilled off in vacuo ο the residue was taken up in water and ether} the ether layer was decanted off and dried over sodium sulphate; The base contained in the solution was a non-crystallizable, oily compound. A solution of hydrochloric acid in ethanol was added to this solution in order to precipitate the hydrochloride of the base. Recrystallized from anhydrous acetone (from 60 ml ^ 2.8 g (65 $ obtained yield) hydrochloride, Schmp.82 ⁰ C. Examples 20 to 26

In a similar way, the symbols below were used in accordance with Formula I identified compounds produced:

Example R

-CH ₂ - ^ y Cl H

- ^CH rC3 ~ ei

Cl

C ₂ H ₅

C ₂ H ₅

C ₂ H ₅ C ₂ H ₅

C ₂ H

H H

6-CF-6-CF.

H 6-CF.

CH ₂ COOC ₂ H ₅

OH

M.p. ⁰ ° C

yield

(Umkr.Lm.) <fo

155 (MeOH) 90

157 (MeOH) 89

116 (MeOH) 66

159 (MeOH) 77

131 (MeOH) 66

132 (MeOH) 55

94 (Äth0H) 79

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BATH ORIGINAL

167Q4S6

The δ-trifluoromethyl-α- 'oxoindoline-3-carboxylate used in Examples 22 to 24 can be prepared in the same manner as described in Sections 2 and 3 of Example 16; the m.p. is 139 C ₀

Example 27 (2-Diethylamino) ethyl 3-benzyl-2-oxoindoline-3-carboxylate A solution of 5.9 g (0.02 mol) of 3-benzyl-2-oxoindoline-3-carboxylate in 50 ml of anhydrous Toluene, which contained 0.02 mol of sodium ethylate, was heated to reflux for 2 hours, then the ethyl alcohol formed was slowly distilled off in 1 hour _o Toluene was distilled off under vacuum, the residue was taken up in water and ether, the ether evaporated and the solid base the isolated base was converted, after recrystallization from methanol m.p. «101 ⁰ G, and was purified by HCl in ether into the hydrochloride. The chlorohydrate (3.9 g) was recrystallized from anhydrous acetone (100 ml); there were g (8i $ yield) 143 ⁰ C of melting point "3.3.
Example 28

Ethyl 3-methyl-2-oxoindoline-3-carboxylate

A mixture of 6.15 g (0.03 mol) of ethyl 2-oxoindoline-3-carboxylate, described in Example 16, 5.7 g (0.04 mol) of methyl iodide and 4.2 g (0.03 mol) anhydrous potassium carbonate in 40 ml of dimethylformamide was ^{stirred at 20 °} C. for 15 hours. The solid was filtered off and the filtrate was evaporated in vacuo to remove the solvent and excess methyl iodide. The solid was collected and purified by washing with water. 5.9 g (90fo yield) of the 3-methyl compound, mp. 82 ⁰ C were obtained. After recrystallization from 20 ml of CCl. , 5 # gi76 yield) of pure product, identical condition to that of Example 16, Schmp.87 ⁰ C. Example 29

Ethyl 3- (propyn-2-yl) -2-oxoindoline-3-carboxylate

The monosodium derivative was formed from 6.15 g (0.03 mol) of ethyl 2-oxoindoline-3-carboxylate and 0.03 mol of sodium ethylate in 100 ml of anhydrous ethanol. To the suspension of this Nabriumderivats 3.9 g (O, O33 mole) of propargyl bromide was added and the mixture was stirred for 12 hours at 2O ⁰ C. A clear solution was obtained, which was used to remove the solvent and excess

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Propargylbroraids was evaporated in vacuo ₀ The solid residue was taken up in chloroform and water, the Chloroiorraschicht dried and the chloroform evaporated. The desired product was obtained in quantitative yield and was recrystallized from 30 ml of anhydrous methanol; In this way 5.2 g (71 $ yield) of pure product with mp. 163 ⁰ C were obtained.
Example 30

Ethyl 3- (2-nitrobenzyl) -2-oxoindoline-3-carboxylate From 6.15 g (0.03 mol) of ethyl 2-oxoindoline-3-carboxylate, the sodium derivative 5.15 g (0.15 g) was obtained as in Example 29. O3 mole) of 2-NitrooenzylChlorid, iii ethanol dissolved was added, and the Ge, mixing was agitated while being heated for 1 hour at reflux, D ° r TTa triumderivat precipitate had disappeared and new crystals were emerged. The crystallization was completed by cooling the mixture to 0 C, the Peststoff was separated by filtration and washed with water to dissolve the NaCl was 7.1g (# 7O yield) of essentially pure product, mp 187 ⁰ C _e. 6.2 g of pure product with a pale melting point were obtained by recrystallization from 40 ml of acetone.
Example 31

Ethyl 3- (2-piperidinoethyl) -2-oxoindoline-3-carboxylate and its Hydrochloride

The sodium derivative was formed as in Example 29 from 10.3 g (0.05 mol) (ethyl 2-oxoindoline-3-carboxylate, drained and washed with dioxane. A suspension of this sodium derivative in 100 ml of anhydrous dioxane was 7.4 g treated (0.05 mol) of 2- (i-piperidino) -1-chloroethane for 24 hours at 20 ⁰ C under stirring, the insoluble portion was filtered off, the Piltrat evaporated in vacuo and the residue taken up in ether and water »the ether layer was dried and the ether evaporated; the desired amino compound was obtained as an oil, which crystallized; yield 10.5 g ($ 67), melting point, 115 ° C. The hydrochloride of the base was formed by adding the theoretical amount of HCl in anhydrous ether and recrystallization from anhydrous isopropanol (50 ml). Pure hydrochloride, (# yield), melting point i80 ° C., decomposition ₀ ) was obtained.

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RAO ORIGINAL

Example 32

Ethyl-i-benzyl ^ -methyl ^ -oxoindoline ^ -oarboxylate From 4.4 g (0.02 mol) of the 3-methyl-2-oxoindoline-3-carboxylate described in Example 28 and 0.022 mol of sodium ethylate in anhydrous ethanol (20 ml), the sodium derivative was prepared, 3.8 g (0.022 mol) of benzyl bromide were added to the solution, and the mixture was refluxed for 2 hours and then concentrated to dryness to remove the solvent. The residue was taken up in ether and water. Evaporation of the ether layer gave 5.9 g (95% yield) of crude product as an oil which crystallized. Recrystallization from 25 ml of 80 volume ethanol gave 4 g (65% yield) of pure product; Mp. 90 ⁰ C.
Examples 33 to 51

In a similar way the following compounds were made, which are identified by their symbols according to formula I:

Example RR ¹ R ² XY m.p. ⁰ C yield

p. ( Umkr.Lm.)

33 C ₂ H ₅ -CH ₂ -CH = CH ₂ HHH 99 (CyClOh ₆ X- 65

"" an + CHCl ₁ ) CH (CH-J ₉ 3 ⁷

34 C ₂ H ₅ - (CH) ₂ -Ii ^j ; fiCl HHH 179 (acetone) 60

CH (CHO

35 C ₂ H ₅ -CH ₂ - ^ y HHH 162 (MeOH) 61

36 C ₂ H ₅ -CH ₂ - / \ H 4 -OCH ₃ H 114 (MeOH ₊ H ₂ O) 92

37 C _n H _c -CH ^ - / \ H 5-OCH ₃ H 122 (MeOH ₊ H ₂ O) -d ° -

an + CHCl-.) 72

38 u _o h _c -CH ,, - // \\ H 6-OCH, H 107 (cyclohex-

^J an + CHCl.)

39 C ₂ H ₅ -CH ₂ - ^ X ^ η 6-OCH ₃ H 137 (MeOH) 68

2 0 9 8 1 5/1 _{7 U Bad ohiqi Nal}

Example R

R ¹

R ² XY m.p. ° C yield

C ₂ H ₅ -CH ₂

C ₂ H ₅ -CH ₂ -COOC ₂ H ₅

C ₂ H ₅ -CH ₂ -

H 6-CH ₃ H 151 (MeOH)

H 4-Cl H 174 (MeOH)

H 4-Cl H 131 (MeOH)

H 6-Cl H 177 (MeOH)

Cl H 6-Cl H 159 (MeOH)

67

70 56

61 54

Cl H 6-CP ₃ H 171 (MeOH) 83 C ₂ H ₅ -CH ₂ -CH ₂ -N (C ₂ H ₅ ) ₂ HCl H 6-Cl H 156 (acetone) 74

C ₂ H ₅ -CH ₂ -CH ₂ -N (C ₂ H ₅ ) ₂ H 6 -OCH ₃ H 190 (acetone) 60

• HCl

H 6 _{-OCH 3} H 124 (MeOH + H ₂ O) 52

HH H 89 (Me0H + H ₂ 0) 54

H 6-Cl H 148 (MeOH) 85

C ₂ H ₅ CH ₃

C ₂ H ₅ CH ₂ -CH ₂ -OH

C ₂ H ₅ CH ₃

51 C _O H CH _{K 9 0} Hp -COOC H 4-OCH, H 140 (Me0H + H _o 0) 58

The xthyloxoindoline carboxylates used as starting materials in Examples 38,39f50 and 41-48 are described in CRAcad.des Sciences, Series C, £ 64 ^ 1075 (1967). The other may be similarly prepared from corresponding Athylphenylmalonaten · ethyl-4-methoxy "has 2-oxoindolin-3-cartooxylat m.p. · of 13O ⁰ Cj the isomeric 5-methoxy compound has a m.p. · of 93 ⁰ C, and the corresponding 6-methyl compound has a mp. of 130 ⁰ C.

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BATH ORIGINAL

Claims (6)

Claims Ί670Α96 1. 2-oxoindoline-3-carboxylic acids and esters of the general ones formula COOH (D in which R and R ¹ each represents a Wasserst off atom or unsubsti _{fc-substituted} or substituted alkyl or aralkyl group or atom form "together with COO and the ring carbon atom 3 of a lactone ring of 5 or 6 members einschliessUci. the ring oxygen, R ² is a OH -Group or represents the same radicals as R and R ^, and X and Y each represent hydrogen or a halogen atom or an alkyl or alkoxy group having 1 to 5 carbon atoms or an aralkoxy, irifluoromethyl, hydroxy, amino or sulfamido group · 2. As compounds according to claim 1s Methyl 2-oxoindoline-3-oarboxylate, ethyl 6-methoxy, 1-hydroxy, 6-chloro, 6-trifluoromethyl, 4-chloro, 3-methyl-6-trifluoromethyl, 3-ethyl-6 -trifluoromethyl-, 1-hydroxy-4-chloro- _t 4-ChIOr ₁ 4-methoxy-, 4-methoxy-, 5-methoxy-, 6-methyl-, 6-dimethylamidosulfonyl-, 3-ethyl-6-amino- , 3-methyl-, 3-benzyl-, 3- (2-diethylaminoethyl, 1- (2-diethylaminoethyl) -, 3-benzyl-, 3 - (^ 4— dichlorobenzyl) -, 3- (3f4-dichlorobenzyl) -, 3-Ethyl-6-trifluoromethyl, 3-benzyl-6-trifluoromethyl, 3-methyl-6-trifluoromethyl, 3-benzyl-1-methyl, 3-carbethoxymethyl, 3- (Propya -2-yl) -, 3- (2-nitrobenzyl) -, 3- (2-piperidinoethyl) -, 1-benzyl-3-methyl-, 3- (propen-2-yl) -, 3-i2- Chlorobenzyl-3-benzyl-4-methoxy-, 3-benzyl-5-methoxy-, 3-benzyl-6-methoxy-, 3- (p-chlorobenzyl) -6-methoxy-, 3-benzyl-6-methyl- , 3-BBnZyI ^ -ChIor-, 3-Carbäthoxymethyl-4-öhlor-, 3-benzyl-6-chloro-, 3-P-ChIo ^ BnZyI-O-ChIor-, 3-p-chlorobenzyl-6-trifluoromethyl- , 3-methyl-6-methoxy-, 3- (2-hydroxyethyl) -, 3-methyl-6-chloro- and 3-carbethoxymethyl-4-methoxy-2-oxoindoli n-3-carboxylate, 209815 / 17U BADORIG.NAL (2-Diethylaminoethyl) -S-benzyl ^ -oxoindoline ^ -carboxylate, ethyl 3- (2-diisopropylaminoethyl) -2-oxoindoline-3-carboxylate hydrochloride Ethyl 3- (2-diethylaminoethyl) -6-chloro-2-oxoindoline-3-carboxylate hydrochloride, and ethyl 3- (2-diethylaminoethyl) -6-methoxy-2-oxoindoline-3-carboxylate hydrochloride. 3. Process for the preparation of a compound according to claim 1, formula I, characterized in that a 2- (2-nitrophenyl) malonic acid compound is used the formula (II) 1 1 in which R and R have the meaning given above and X and Y are the same as X and Y or a NOp group, reduced. 4. The method according to claim 3> characterized in that the Carries out reduction by means of hydrogen in the presence of a hydrogenation catalyst. 5. The method according to claim 3, characterized in that the Reduction by means of a reducing compound which is effective in neutral, acidic or alkaline madium. 6. The method according to claim 3, characterized in that a compound according to formula I is prepared in which R ^{2 is} hydrogen, whereupon this compound is alkylated or aralkylated. For CENTER NATIONAL DE LA RECHERCHE SCIENTIFIQUE PARIS, FRANCE Attorney 209815 / 17U