NL9001162A - PROCESS FOR PREPARING 2-N-ACYLAMINOPYRIDINES AND 2-AMINOPYRIDINES FROM 5-OXOALCANE NITRILOXIMMS AND THESE 5-OXOALCANE NITRILOXIMMS, 2-N-ACYLAMINOPYRIDINES AND 2-AMINOPYRIDINES - Google Patents

Description

Inventors: Anna M.C.F. Castelijns in Stein Peter J.D. Maas te Schinnen Henricus J. Arts at Sittard Robert J. Vijn at Geleen -1- (26) PROCESS FOR THE PREPARATION OF 2-N-ACYLAMINOPYRIDINES AND 2-AMINOPYRIDINES FROM 5-0X0ALKANE NITRILOXIMMS AND THESE 5-0X0ALKAANNITRIL,

2-N-ACYLAMINOPYRIDINES AND 2-AMINOPYRIDINES

The invention relates to a process for the preparation of 2-N-acylaminopyridines.

There is a great need for simple and inexpensive preparation methods for 2-N-acylamino pyridines, which compounds can be used as raw materials for pharmaceutical and agrochemical intermediates and end products.

The known preparation methods for 2-N-acylamino-pyridines are based on the acylation of the corresponding 2-aminopyridines. For example, the 2-aminopyridines required for this synthesis are prepared in the manner described in DE-C-374291. In this method, a pyridine is aminated with a sodium amide of the general formula NaNHR, wherein R is hydrogen, aryl, alkyl or a heterocyclic group such as pyridyl or quinolyl, or with a mixture of metallic sodium and a primary amine. The reaction generally lasts more than 5 hours.

The known methods of obtaining 2-N-acylaminopyridines have the drawback that they all pass through a 2-amino-pyridine, which is obtained by amination of the corresponding pyridine.

The pyridines which are the raw material in the preparation of these 2-aminopyridines are often difficult or inaccessible at all and the amination reaction takes a long time.

In addition, these preparation methods require large material flows, which is not economically attractive.

The method according to the invention aims to avoid these disadvantages and limitations.

To this end, a 2-N-acylamino pyridine is prepared with

formula 1 formula 1 wherein R ^ and = an alkyl group, a cycloalkyl group, an aryl group, or a heteroaryl group, R2 / Rg and R ^ = hydrogen, an alkoxy group, an aryl group, a heteroaryl group, an alkyl group, or a cycloalkyl group and wherein R ^ and R2 together can form a cycloalkyl group, through a 5-oxoalkanitrile oxime of formula 2

formula 2 wherein R 1 through R 2 have the above-described meaning, in the presence of a strong acid, to be treated with an acylating agent containing at least one R 1 -group of the above-described meaning.

In addition, the invention relates to a process for preparing 2-aminopyridines from the 2-N-acylaminopyridines thus obtained.

A large number of 2-aminopyridines are raw materials for pharmaceutical and agrochemical intermediates and end products. For example, 2-amino-6-methylpyridine is used in the preparation of nalidixic acid. Nalidixic acid is a chemothe rapeuti cum.

An important, known preparation method for the preparation of 2-aminopyridines and the associated drawbacks has already been described above.

These drawbacks are prevented, since the deacylation reaction in preparation via the 2-N-acyl-aminopyridines is very simple, when a 2-N-acylaminopyridine of the formula 1 obtained according to the process of the invention is converted into a 2-aminopyridine with formula 3

formula 3 wherein R ^ to R ^ have the meanings described above.

The groups R1 to Rg in formulas 1-3 and in formulas 4 and 5 to be discussed below may have the previously described meaning. R ^, Rg, R ^ and Rg may be substituted. As optional substituents in the groups R1 through Rg, all substituents that are inert under the reaction conditions can be used, such as halides, alkoxy groups, alkyl groups and aryl groups. R1 to R5 should not be too large for the process to run smoothly. The size of each of R1 to R5 will therefore usually be limited to 15 carbon atoms. Examples of R.-R.-

1 O

are: methyl, ethyl, propyl, decyl, isobutyl, phenyl, chlorophenyl, methylcyclohexyl, benzyl, trifluoromethyl, methoxyphenyl, pyridyl. Examples of R2-R4 are additionally: methoxy, ethoxy, butoxy, phenoxy, chloromethoxy.

The 5-oxoalkanitrile oximines which are used as starting compounds in the process according to the invention are the oximes of the formula II.

formula 2 in which R ^ to the above-mentioned meaning.

Examples of such 5-oxoalkanitrile oximes are: 5-oxohexanitrile oxime 4-methyl-5-oxohexanitrile oxime 2-methyl-5-oxoheptanitrile oxime 2,4-dimethyl-5-oxohexane nitrile oxime 3-methyl-5-oxohexane nitrile oximethyl-2-oxoxy-4-methoxy (2-cyaphioethyl) -cyclohexanone oxime 2- (2-cyanopropyl) -cyclohexanone oxime 2- (2-cyanoethyl) -4-methyl-cyclohexanone oxime 2- (2-cyanoethyl) -4-methoxy-cyclohexanone oxime 2- (1-methyl-2 -cyanoethyl) -6-methyl-cyclohexanone oxime 2- (2-cyanoethyl) cyclopentanone oxime 2- (1-methyl-2-cyanoethyl) cyclopentanone oxime 2- (2-cyanoethyl) -5-methyl-cyclopentanone oxime.

The oximes can be made in any suitable way. For example, it is possible to make the 5-oxoalkanitrile oximes by reacting a 5-oxoalkanitrile with hydroxylammonium sulfate and treating this mixture with caustic. It is also possible to make 5-oxoalkanitrile oximes with this process, where R 2 is an unsubstituted or substituted acyl group, or R 2 is H.

Examples of these are 5-oxopentanitrile oxime, 4-methyl-5-oxopentanitrile oxime, 2 methyl-5-oxopentanitrile oxime, 3-itethoxy-4-methyl-5-oxopentanitrile oxime.

The invention also relates to the aforementioned 5-oxoalkanitrile oximes.

2-N-acylaminopyridioes can be made by the method according to the invention. Examples include: 2-N-acetylamino-6-methylpyridine 2-N-chloroacetylamino-6-methylpyridine 2-N-benzoylamino-6-methylpyridine 2-N-acetylamino-5,6-dimethylpyridine 2-N-acetylamino-3, 5,6-trimethylpyridine 2-N-chloroacetylamino-3,5,6-trimethylpyridine 2-N-acetylamino-3-methyl-6-ethylpyridine 2-N- (2-chlorobenzoylamino) -4,6-dimethylpyridine 2-N- acetylamino-5-methoxy-6-methyl-pyridine 2-N-acetylamino-5,6,7,8-tetrahydroquinoline 2-N- (p-methoxybenzoylamino) -3-methyl-5,6,7,8-tetrahydroquinoline 2 -N-acetylamino-6-methyl-5,6,7,8-tetrahydroquinoline 2-N-chloroacetylamino-6-methoxy-5,6,7,8-tetrahydroquinoline 2-N-acetylamino-4,8-dimethyl-5 6,7,8-tetrahydroquinoline 2-N-acetylamino-5,6-cyclopentenopyridine 2-N-acetylamino-3-methyl-5,6-cyclopentenopyridine.

2-Aminopyridines can also be made. Examples include: 2-amino-6-methylpyridine 2-amino-5,6-dimethylpyridine 2-amino-3,5,6-trimethylpyridine 2-amino-6-ethylpyridine 2-amino-3-methyl-6-ethylpyridine 2 -amino-3-trifluoromethyl-6-ethylpyridine 2-amino-4,6-dimethylpyridine 2-amino-4,5,6-trimethylpyridine 2-amino-6-isopropylpyridine 2-amino-5-methoxy-6-methylpyridine 2- amino-5,6,7,8-tetrahydroquinoline 2-amino-4-methyl-5,6,7,8-tetrahydroquinoline 2-amino-4,6-dimethyl-5,6,7,8-tetrahydroquinoline 2-amino -5-methoxy-5,6,7,8-tetrahydroquinoline 2-amino-5,6-cyclopentenopyridine 2-amino-3-methyl-S. 6-cyclopentenopyridine.

The invention also relates to 2-N-acylamino pyridines of general formula 1 wherein R 1 to R have the meaning previously described except for the known compound wherein R 1 to R 1. simultaneously have the following meanings: * 1 = CHg, R2 = H and R5 = CH ^. In addition, the invention relates to 2-aminopyridines of general formula 3 wherein R 1 to R 2 have the meaning previously described with the exception of the known compound wherein R 1 = CH 3 and R 2 to R 4 = H and the known compound at the same time at the same time R ^ R2 and R4 = CH3 and R3 = H, the known compound where at the same time R1 and R2 = CH3 and R3 and R ^ = H, the known compound at the same time where Rx and R4 = CH3 and R2 and R3 = H as well as the known compound where R ^ = CH3, R3 = CH3 ~ CH -CH3 and R2 and R4 = H. ^

In the method according to the invention, the 5-oxoalkanitrile oximes are treated in the presence of a strong acid with an acylating agent containing at least one Back group with the meaning described above. The strong acid to be present can be formed in situ or added as such to the reaction mixture. As the acylating agent, an agent can be used which is an acid halide of the formula '4,

formula 4 wherein R5 has the aforementioned meaning and X is a halogen atom, or a combination of an acid halide of formula 4 and a carboxylic anhydride of formula 5,

formula 5, wherein and R "5 are the same groups as described for R 2 and R" and R ". can form a ring together.

Strong acid is formed in situ both when using an acid halide and when using an acid halide with an acid anhydride. It is also possible to use a carboxylic anhydride of formula 5 as an acylating agent and to add a strong acid as such to the reaction mixture, preferably a halogen acid, with hydrochloric acid being particularly preferred.

Preferably, the acylating agent used is the combination of an acid chloride and an anhydride as described above. Especially preferred is the combination of acetyl chloride and acetic anhydride. If one is only interested in the preparation of a 2-aminopyridine, it is not important that R '^ and R "g are the same, because the acyl residue is then nevertheless removed. In the preparation of a 2-N-acylaminopyridine, one will preferably R '^. And R "j. choose immediately because otherwise a mixture of two 2-N-acylaminopyridines is obtained.

A large number of embodiments of the method are possible. Examples of suitable embodiments are the following:

Synthesis of 2-N-acylaminopyridines

The oxime is dissolved in a carboxylic anhydride. Preferably, 2-6 molar equivalents of carboxylic anhydride relative to the amount of oxime are used and more particularly 2-3 molar equivalents.

The temperature during dissolution can vary within wide limits. Preferably, however, it is kept between -10 ° C and 20 ° C. A temperature of 0-5 ° C is particularly preferred.

The solution is then heated and HCl gas is passed during heating.

The temperature of the reaction mixture is finally kept between 80 and 135 ° C. Preferably between 95 and 105 ° C.

The flow rate of the HCl gas can vary within wide limits. Generally, the gas flow is chosen to be so large that 3-4 hours pass through is sufficient for complete conversion of the oxime.

The 2-N-acylaminopyridine formed can now be recovered, for example, by crystallization.

In another method, the oxime is dissolved in 1-4 molar equivalents of carboxylic anhydride over the oxime. 1-2 molar equivalents of carboxylic anhydride are preferably used. The temperature during dissolution can vary within wide limits. Preferably, however, it is kept between -10 ° C and 20 ° C. A temperature of 0-5 ° C is particularly preferred.

Carboxylic acid chloride is then dosed in an amount of at least 1 molar equivalent to the oxime. Preferably 1-4 molar equivalents are used and particularly preferred is 1-2 molar equivalents.

The solution is then heated to a temperature above 40 ° C and preferably above 80 ° C.

A temperature of 90-110 ° C is particularly preferred. The duration of the heating depends on a number of factors, including the temperature, but it is usually between 3 and 4 hours.

The 2-N-acylaminopyridine can be recovered by distillation or crystallization.

Synthesis of 2-aiainopyridine

If desired, the 2-N-acylaminopyridines obtained by the process according to the invention can be converted into the corresponding 2-aminopyridines in a manner known per se.

To this end, the reaction mixture can, for example, be treated with a strong base such as caustic. The 2-aminopyridine formed can then be recovered by distillation or crystallization.

Example 1

Preparation of 5-oxohexanitrile oxime 37.0 grams (0.45 mol) of hydroxylammonium sulfate was dissolved in 75 ml of water. 50.2 grams (0.45 mol) of 5-oxohexanitrile were metered into this solution. The resulting mixture was then cooled to about 10 ° C, after which, while stirring and cooling, 18.0 grams of NaOH (0.45 mol) was metered into 35 ml of water (dosing time: 25 minutes). During this dosing, care was taken to ensure that the temperature of the reaction mixture did not rise above 20 ° C. After the dosing was completed, the reaction mixture was stirred at room temperature for 2 hours. After demixing, the organic phase was separated from the water phase. The water phase was then extracted with diethyl ether. The combined organic phases were then dried over MgSO4. After filtering out the MgSO4, the filtrate was evaporated on a rotary evaporator.

In this way, 48.1 grams of 5-oxohexanitritrile oxime were obtained with a purity of 99% (Yield: 84%).

The following values were measured with H-NMR:

1 H NMR (CDCl 3 / TMS): δ = 1.5-2.1 m; 6p; Ha + Hd + Hb δ = 2.1-2.6 m; 4p; HC + He

The notation used when displaying the 1 H-NMR results has the following meaning: p = proton s = singlet d = doublet t = triplet q = quartet m = multiplet -.

(b) = wide

Example 2

Preparation of 2-methyl-5-oxoheptanitrile oxime

The preparation was done analogous to example 1, starting from 2-methyl-5-oxoheptanitrile. Purity: 94%. Yield: 97%

1 H NMR (CDCl 3 / TMS): δ = 0.90 - 1.33; m; 6p; Ha + Hb

δ = 1.79; m; 2p; HC

δ = 2.08-2.68; m; 5p; Hd + He + Hf δ = 4.90; s (b); lp; Hh

Example 3

Preparation of 2,4-dimethyl-5-oxo-hexanitrile oxime

The preparation was done analogous to example 1, starting from 2,4-dimethyl-5-oxohexanitrile.

Yield: 93%. Purity 95%.

Example 4

Preparation 2- (2-cyanoethyl) -cyclopentanone oxime 25.8 grams (0.31 mol) of hydroxylammonium sulfate was dissolved in 50 ml of water. 27.3 grams (0.2 mol) of 2- (2-cyanoethyl) -cyclopentanone dissolved in 50 ml of diethyl ether were dosed to this solution. The resulting mixture was then cooled to 10 ° C, after which, while stirring and cooling, 12.0 g (0.3 mole) of NaOH was metered into 40 ml of ^ 0 (dosing time: 20 minutes). During this dosing, care was taken to ensure that the temperature of the reaction mixture did not rise above 20 ° C.

After the dosing was complete, the reaction mixture was stirred at room temperature for 16 hours. After separation, the ether phase was separated from the water phase. The water phase was then extracted with diethyl ether. The combined ether phases were then dried over MgSO4. After filtering out the MgSO4, the filtrate was evaporated on a rotary evaporator.

In this way, 26.2 grams of 2- (2-cyanoethyl) -cyclopentanone oxime were obtained with a purity of 99%. Yield 86%.

Example 5

Preparation of 2- (2-cyanoethyl) -cyclohexanone oxime

The preparation was done analogous to example 4, but starting from 2- (2-cyanoethyl) cyclohexanone.

Yield: 59%. Purity: 75%.

1 H-NMR (CDCl 3 / TMS): δ = 1.5-2.0; m; 9p; Ha δ = 2.15-2.69; m; 4p; Hb + Hc δ = 6.68-8.34; s (b); lp; Hd

Example 6

Preparation of 4-acetyl-5-oxohexanitrile oxime

The preparation was done analogous to example 4, starting from 4-acetyl-5-oxohexanitrile.

Yield 86%. Purity: 84%.

Example 7

Preparation of 5-oxopentanitrile oxime.

The preparation was done analogous to example 4, starting from 5-oxopentanitrile.

Yield 81%. Purity: 93%.

1 H NMR (CDCl3 / TMS): δ = 1.60 - 2.09; m; 2p; Ha δ = 2.10 - 2.68; m (b); 4p; Hb + HC δ = 4.60; s (b); lp; Hd δ = 6.63 and 7.31; t; lp; He (E + Z isomers)

Example 8

Preparation 2-N-acetylamino-6-methylpyridine

To 12.6 grams of 5-oxohexanitrile oxime (0.1 mol) was added 10.2 grams of acetic anhydride (0.1 mol) while cooling with a water / ice bath and stirring. At a temperature of about 5 ° C, 10.2 g of acetyl chloride (0.13 mol) was metered in over 15 minutes with continued cooling in the water / ice bath. The reaction mixture was then heated to reflux temperature. After reaching a reflux temperature of about 100 ° C, the reaction mixture was kept at this temperature. The total reaction time after the reflux temperature was reached was 4 hours. Then the reaction mixture was cooled to room temperature and poured into 100 ml water. The aqueous solution was neutralized with a 33 wt.% NaOH-x solution and then extracted 4x with 50 ml Cl 2 Cl. After drying and evaporation of the organic phase, 10.3 g of 2-N-acetylamino-6-methylpyridine were obtained in a yield of 69% relative to the oxime. Mp. 84.5-86 ° C.

1 H NMR (CDCl 3 / TMS): δ = 2.26; s; 3p; Ha δ = 2.42; s; 3p; Hb

δ = 6.80; d; lp; HC

δ = 7.50; t; lp; He δ = 7.97; d; lp; Hd δ = 8.90; s (b); lp;

Example 9

Preparation of 2-N-acetylamino-5,6-cyclopentenopyridine To 8.0 grams (0.05 mol) 2- (2-cyanoethyl) cyclopentanone oxime was added 25.0 g (0.25 mol) acetic anhydride. HCl gas was introduced at a temperature of 18-22 ° C under cooling in a water / ice bath for 5 hours. The reaction mixture was stirred at room temperature for 16 hours. 75 ml of water were added to the reaction mixture, after which it was extracted 4 times with 35 ml of dichloromethane. Yield: 5%. Mp: 117.5-118 ° C.

1 H-NMR (CHCl 3 / TMS) δ = 2.08; s 3p; He δ = 2.78; m (b); 8p; Ha δ = 8.75; s (b); lp; Hb

δ = 7.37; d; lp; HC

δ = 7.82; d; lp; Hd

Example 10

Preparation 2-amino-6-methylpyridine

While cooling in a water / ice bath, 23.5 grams (0.23 mol) of acetic anhydride was added to 12.6 grams (0.1 mole) of 5-oxohexanitrile oxime with stirring. Then, the reaction mixture was heated to reflux for 4 hours while passing HCl gas simultaneously, the reflux temperature rising to about 100 ° C.

Then the reaction mixture was cooled to about 50 ° C, after which a solution of 26.4 g (0.66 mol) of NaOH in 75 ml of water was metered and then the mixture was stirred at 70 ° C for 1 hour. The reaction mixture was then cooled to room temperature and extracted 4x with 50 ml of dichloromethane. After drying and evaporation, 5.9 g of 2-amino-6-methylpyridine were obtained in a yield of 55% relative to the oxime.

Example 11

Preparation 2-amino-6-methylpyridine

Under cooling in a water / ice bath, 10/2 grams (0.1 mol) acetic anhydride was added to 12.6 grams (0.1 mole) of 5-oxohexanitrile oxime with stirring. At a temperature of about 5 ° C, 10.2 g (0.13 mol) of acetyl chloride were metered in over 20 minutes with cooling in a water / ice bath and stirring. The reaction mixture was then heated to reflux for 4 hours with the reflux temperature rising from 80 ° C to about 130 ° C.

Subsequently, the reaction mixture was cooled to 50 ° C, after which a solution of 26.4 g (0.66 mol) of NaOH in 75 ml of water was metered and then stirred at 70 ° C for 1 hour. The reaction mixture was then cooled to room temperature and extracted 4x with 50 ml of dichloromethane. After drying and evaporation of the organic phase, 6.3 g of 2-amino-6-methyl-pyridine were obtained in a yield of 58% with respect to the oxime. Mp: 41.2-42.4 ° C

1 H NMR (CDCl 3 / TMS): δ = 2.35; s; 3p; Ha δ = 4.80; s (b); 2p; Hb δ = 6.17; d; and 6.34; d; 2p; Hc + Hd δ = 7.15; t; lp; Ηβ

Example 12

Preparation of 2-amino-6-methylpyridine To 12.6 g of 5-oxohexanitrile oxime (0.10 mol) was added 40.5 g of chloroacetic anhydride (0.24 mol). Subsequently, introduction of HCl gas was started with simultaneous heating to 85 ° C. During the first 45 minutes, the temperature was adjusted by kept a little cooling between 80 and 95 ° C. Then the temp. held at 95 ° C for 3.5 hours. HCl was initiated throughout the experiment. The reaction mixture was then cooled to room temperature, after which a solution of 14 g NaOH (0.35 mol) in 75 ml water was added. After this, 40 ml of ethanol was added (adding ethanol gives a homogeneous reaction mixture during the hydrolysis). The reaction mixture was then heated to reflux temperature for 2 hours. Then it was cooled to room temperature after which the reaction mixture was extracted with 4 x 50 ml of dichloromethane. After drying and evaporation of the organic phase, the 2-amino-6-methylpyridine was obtained with a yield of 15% relative to the oxime.

Example 13

Preparation of 2-amino-6-methylpyridine of 18.0 g of 5-oxohexanitrile oxime (0.14 mol), 32.5 g of benzoic anhydride (0.14 mol) were added.

This mixture was heated to 100 ° C. At 100 ° C, 26.8 g of benzoyl chloride (0.19 mol) was dosed over a period of 14 min. cooling briefly with a water bath to prevent the temperature rising to above 115 ° C.

After all the benzoyl chloride was added, the temperature was kept at about 100 ° C for another 4 hours. Then it was cooled to room temperature. A solution of 15 g NaOH (0.38 mol) in 50 ml water and 50 ml ethanol was added to the reaction mixture.

The reaction mixture was kept at reflux temperature for 2 hours. Then it was cooled to room temperature and extracted 4 times with 50 ml of dichloromethane. After drying and evaporation of the organic phase, the -2-amino-6-methylpyridine was obtained with a yield of 7% relative to the oxime.

Example 14

Preparation of 2-amino-6-methylpyridine

52.0 g of benzoic anhydride (0.23 mol) were added to 12.6 g of 5-oxohexanitrile oxime (0.10 mol). Simultaneous introduction of HCl gas and heating to 100 ° C was started. HCl gas was introduced at 100 ° C for 4 hours. Then it was cooled to 50 ° C (At a lower temperature, the reaction mixture would solidify).

A solution of 30 g of NaOH (0.75 mol) in 100 ml of water and 50 ml of ethanol was added to the reaction mixture. The reaction mixture was kept at reflux temperature for 2 hours. Then 50 ml of water was added, otherwise an inhomogeneous mixture is obtained on cooling. Then it was cooled to room temperature and extracted 4 times with 50 ml of dichloromethane. After drying and evaporation of the organic phase, the 2-amino-6-methylpyridine was obtained with a yield of 28.1%.

In an analogous manner to Example 11, the following products were synthesized:

Example 15 2-amino-3,5,6-trimethylpyridine bpt 110 ° C (14.5 mlHg); m.p. 99-102 ° C Efficiency: 63%

1 H NMR (CDCl3 / TMS): δ = 2.02 s; 2.11 s; 2.28 s; 9p; Ha + Hb + HC δ = 4.25 s (b); 2p; Hd δ = 6.90 s; lp; Hey

Example 16 2-amino-5,6,7,8-tetrahydroquinoline Mp: 60.5 - 62.5 ° C Efficiency: = 43%

1 H 1 NMR (CDCl 3 / TMS): δ = 1.78; m (b); 2.66 m (b): 8p; Ha δ = 4.33; s (b); 2p; Hb

δ = 6.22; d: lp; HC

δ = 7.05; d; lp; Hd

Example 17 2-amino-3-methyl-6-ethylpyridine

Kpt. 68-70 ° C (0.55mm Hg) Efficiency: = 43%

1 H NMR (CDCl 3 / TMS): δ = 1.24 t; 3p; Ha δ = 2.03 s; 3p; Hb

δ = 2.60 q; 2p; HC

δ = 4.60 s (b): 2p; Hd δ = 6.38 d; lp; He δ = 7.08 d; lp; Hf

Claims (2)

1. Process for the preparation of 2-N-acylaminopyridines, characterized in that a 2-N-acylaminopyridine according to formula 1

formula 1 wherein R 1 and R 5 = an alkyl group, a cycloalkyl group, an aryl group, or a heteroaryl group, R 2, R 3 and R 4 = hydrogen, an alkoxy group, one aryl group, a heteroaryl group, an alkyl group, or a cycloalkyl group and wherein R 1 and R 2 together a cycloalkyl group prepared by a 5-oxoalkanitrile oxime of formula 2

formula 2 wherein R 1 through R 2 have the above-described meaning, in the presence of a strong acid, to be treated with an acylating agent containing at least one R 2-group of the above-described meaning. 2. Process according to claim 1, characterized in that the acylating agent is an acid halide of the formula IV

formula 4 wherein R ^ has the meaning described above and X is a halogen atom. Process according to claim 1 or 2, characterized in that a carboxylic anhydride of the formula 5 is also present

formula 5 wherein R 1 'and R "1 are the same groups as described for R 1, and R' 1 and R" 1 together may form a ring. 4. Process according to claim 3, characterized in that in the carboxylic anhydride of formula 5 R'5 is equal to R "-. Process according to claim 3 or 4, characterized in that the 5-oxoalkanitrile oxime is dissolved in a carboxylic anhydride of the formula 5 and then an acid chloride of the formula 4 is dosed. 6. Process according to any one of claims 3-5, characterized in that the amount of carboxylic anhydride of formula 5 is 1-4 mole equivalents relative to the 5-oxoalkanitrile oxime and that the amount of acid chloride of formula 4 is 1-4 mole equivalents relative to the 5-oxoalkanitrile oxime . A method according to any one of claims 3-6, characterized in that the carboxylic anhydride is acetic anhydride. Process according to claim 3, characterized in that the strong acid is added as such to the reaction mixture. Process according to claim 8, characterized in that the 5-oxoalkanitrile oxime is dissolved in a carboxylic anhydride of formula 5, after which the solution is contacted with the strong acid. Process according to claim 9, characterized in that the 5-oxoalkanitrile oxime is dissolved in 2-6 molar equivalents of carboxylic anhydride of formula 5. A method according to any one of claims 1-10, characterized in that the strong acid is hydrochloric acid. Process for the preparation of 2-aminopyridines, characterized in that a 2-N-acylaminopyridine of the formula 2 prepared according to any one of claims 1 to 11 is converted into a 2-aminopyridine of the formula 3

formula 3 wherein to R 1 have the meanings described above. 13. 5-Oxoalkanitrile oximes of formula 2

formula 2 wherein R1 = hydrogen, an alkyl group, a cycloalkyl group, an aryl group, or a heteroaryl group, R2 = hydrogen, an alkoxy group, an aryl group, an acyl group, a heteroaryl group, an alkyl group, or a cycloalkyl group and wherein and R2 together form a cycloalkyl group R 8 and R 8 = hydrogen, an alkoxy group, an aryl group, a heteroaryl group, an alkyl group, or a cycloalkyl group R 5 = an alkyl group, a cycloalkyl group, an aryl group or a heteroaryl group. The process for preparing 5-oxoalkanitrile oximes according to claim 13, characterized in that a 5-oxoalkanitrile is treated with hydroxylammonium sulfate and caustic. 15. 2-N-acylaminopyridines of formula 1,

formula 1 wherein R 1 and R 5 = an alkyl group, a cycloalkyl group, an aryl group, or a heteroaryl group, R 2, R 8 and R 5 = hydrogen, an alkoxy group, an aryl group, a heteroaryl group, an alkyl group, or a cycloalkyl group and wherein R 4 and R 2 together may form a cycloalkyl group, except for the compound wherein R 1 to R 5 simultaneously have the following meanings: R 1 = CH 2, R 2 to R 4 = H and R 5 = CH 3 16. 2-Aminopyridines of formula 3 formula 3

wherein R 1 = an alkyl group, a cycloalkyl group, an aryl group, or a heteroaryl group, R 2, R 3 and R 4 = hydrogen, an alkoxy group, an aryl group, a heteroaryl group, an alkyl group, or a cycloalkyl group, and wherein R 1 and R 2 together may form a cycloalkyl group , with the exception of the compound in which R1 = CH3 and R2 to R ^ = κ at the same time and the compound in which R ^, R2 and R ^ = ch3 and R3 = H simultaneously, the known compound in which R1 and R2 = CH3 and R3 and R ^ = H, the known compound, wherein ^ and R4 = CH3 and R2 and R3 = h as well as the known compound wherein R ^ = CH3, r3 = and R2 and R ^ = h. 17. Process for the preparation of 2-N-acylaminopyridines, 2 N aminopyridines or 5-oxoalkanitrile oximines as substantially described and illustrated in the examples. EXTRACT The invention relates to a process for the preparation of 2-N-acylaminopyridines of the formula 1

formula 1 wherein R 1 and R 2 = an alkyl group, a cycloalkyl group, an aryl group, or a heteroaryl group, R 2, R 9 and R 2 = hydrogen, an alkoxy group, an aryl group, a heteroaryl group, an alkyl group, or a cycloalkyl group and wherein R 1 and R 2 together may form a cycloalkyl group prepared by a 5-oxoalkanitrile oxime of formula 2

formula 2 wherein R 1 through R 2 have the above-described meaning, in the presence of a strong acid, to be treated with an acylating agent containing at least one-R 2 -group of the above-described meaning. The invention also relates to a process for the preparation of 2-aminopyridines of formula 3

formula 3 in which thru R1 have the above meaning, from the 2-N-acylamino pyridines. The invention also relates to the 5-oxoalkanitrile oximines of formula 2, also those with R 1 = H and R 2 an acyl group, the 2-N-acylaminopyridines of formula 1, and the 2-aminopyridines of formula 3.