WO1993016070A1 - 3-(pyridylamino)-2-(1h^_-tetrazol-5-yl)-acrylnitriles and a process for the preparation thereof - Google Patents
3-(pyridylamino)-2-(1h^_-tetrazol-5-yl)-acrylnitriles and a process for the preparation thereof Download PDFInfo
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- WO1993016070A1 WO1993016070A1 PCT/HU1993/000008 HU9300008W WO9316070A1 WO 1993016070 A1 WO1993016070 A1 WO 1993016070A1 HU 9300008 W HU9300008 W HU 9300008W WO 9316070 A1 WO9316070 A1 WO 9316070A1
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- JNLAUXYVOPBIHX-UHFFFAOYSA-N C=C(Cc1n[nH]nn1)C#N Chemical compound C=C(Cc1n[nH]nn1)C#N JNLAUXYVOPBIHX-UHFFFAOYSA-N 0.000 description 1
- 0 CC(C=C)(C=CC(N*)=NC=*C)*=C Chemical compound CC(C=C)(C=CC(N*)=NC=*C)*=C 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Definitions
- This invention relates to novel 3-(pyridylamino)-2- -(lH-tetrazol-5-yl)-acrylnitriles of general formula (I)
- Our invention is based upon the discovery that the 3-(lH-tetrazol-5-yl)-4H-pyrido[l,2-a]pyrimidin-4-ones of general formula (II) may be prepared in a simple manner and in good yields by the cyclization of the novel 3-(2- pyridylamino)-2-(lH-tetrazol-5-yl)acrylnitriles of gene ⁇ ral formula (I) .
- the subject of our invention are compounds of general formula (I) and the geometric isomers, tautomers and hydrates thereof - wherein
- R stands for hydrogen, C- j ⁇ alkyl, halogen, hydroxy, nitro, carboxy, C2-5 alkoxycarbonyl or c 7-12 aralkoxy;
- R 1 stands for hydrogen, C ⁇ _ 4 alkyl or halogen
- R2 represents hydrogen, ⁇ - ⁇ alkyl or Cg. ⁇ Q aryl - and a -process for the preparation thereof.
- C-j ⁇ alkyl group means - in itself or in moieties, for instance in alkoxy groups - straight or branched chain aliphatic saturated hydro ⁇ carbon groups having one to four carbon atoms (such as e.g. methyl, ethyl, n-propyl and tert.-butyl group).
- Cg_*]_o aryl group means phenyl group or naphthyl group, optionally bearing a C*L_4 alkyl group.
- the present invention also relates to a process for the preparation of compounds of general formula (I) and the geometric isomers, tautomers and hydrates thereof which comprises a) reacting a 3-cyano-4H-pyrido[l,2-a]pyrimidine-4- -imine of general formula (III)
- alkali azide preferably sodium azide is used.
- dipolar aprotic solvents e.g. dimethyl- formamide
- dipolar aprotic solvents e.g. dimethyl- formamide
- the resulting compound of the general formula (I) (wherein R, R 1 and R 2 are the same as above) precipitates from the reaction mixture immediately, or after pouring the reaction mixture onto another solvent mixture.
- the product may be obtained from the reaction mixture by filtration, or after evaporation of the solvent by e.g. distillation.
- the compounds of the general formula (I) (wherein R, R 1 and R 2 are the same as above) thus obtained may be purified by the usual methods (such as for instance re- crystallisation or chromatography) .
- the starting materials of general formulae (III) and (IV) (wherein R, R 1 and R 2 are the same as defined above) are known from the literature (Journal of Organic Chemistry, 1986, 5_1, 2988), or they may be prepared in an analogous way.
- the starting materials of general formulae (V) and (VI) (wherein R, R 1 , R 2 and R 3 are the same as defined above) are available on the market, whereas the compound of general formula (VII) (wherein R 2 and R 3 are the same as defined above) may be prepared by analogy of the known alkoxymethylenemalonitriles.
- [l,2-a]pyrimidine-3-carbonitrile, 16.25 g (0.25 mol) of sodium azide and 13.37 g (0.25 mol) of ammonium chloride are stirred in 250 ml of dimethylformamide at 80 °C for 1 hour.
Abstract
The invention relates to novel 3-(pyridylamino)-2-(1H^_-tetrazol-5-yl)-acrylnitriles of general formula (I), their geometric isomers, tautomers and hydrates and the preparation thereof. These compounds are useful as favorable starting materials to compounds of general formula (II) which possess first of all antiallergic and antiulcer activity. In general formula (I) R stands for hydrogen, C1-4 alkyl, halogen, hydroxy, nitro, carboxy, C2-5 alkoxycarbonyl or C7-12 aralkoxy; R1 stands for hydrogen, C¿1-4? alkyl or halogen; R?2¿ represents hydrogen, C¿1-4? alkyl or C6-10 aryl. The present invention also relates to a process for the preparation of compounds of general formula (I) and the geometric isomers, tautomers and hydrates thereof.
Description
3-(Pyridylamino)-2-(lH-tetrazol-5-yl)-acryl-nitriles and a process for the preparation thereof
This invention relates to novel 3-(pyridylamino)-2- -(lH-tetrazol-5-yl)-acrylnitriles of general formula (I)
and a process for the preparation thereof. These compounds are useful as favourable starting materials to compounds of general formula (II)
It is known that the 3-(lH-tetrazol-5-yl)-4H- pyrido[l,2-a]pyrimidine-4-ones of general formula (II) exert antiallergic and antiulcer activity (US-PS Nos. 4122274 and 4457932) , and their preparation may be accomplished, in poor to sufficient yields, by reacting 3-cyano-4H-pyrido[l,2-a]pyrimidine-4-ones or ethyl-[2- -cyano-3-(2-pyridylamino) ]-acrylates with sodium azide in the presence of aluminium chloride. Another route for the preparation of these compounds is to subject ethyl-[3-(2- -pyridylamino)-2-(lH-tetrazol-5-yl)-acrylates] to cycli- sation in polyphosphoric acid (US-PSo. 4474953) . Disadvantage of the latter process is that under the
applied conditions not only the cyclisation but, to a certain extent, the alkylation of the tetrazole ring also takes place.
Our invention is based upon the discovery that the 3-(lH-tetrazol-5-yl)-4H-pyrido[l,2-a]pyrimidin-4-ones of general formula (II) may be prepared in a simple manner and in good yields by the cyclization of the novel 3-(2- pyridylamino)-2-(lH-tetrazol-5-yl)acrylnitriles of gene¬ ral formula (I) . The subject of our invention are compounds of general formula (I) and the geometric isomers, tautomers and hydrates thereof - wherein
R stands for hydrogen, C-j^ alkyl, halogen, hydroxy, nitro, carboxy, C2-5 alkoxycarbonyl or c7-12 aralkoxy;
R1 stands for hydrogen, Cι_4 alkyl or halogen;
R2 represents hydrogen, ^-^ alkyl or Cg.^Q aryl - and a -process for the preparation thereof.
The structure of the geometric isomers is shown in general formulae (IA) and (IB) . The structure of the tautomers is shown on Schemes A and B.
(IA ) (IB )
Scheme A
Scheme B
As used herein, the term "C-j^ alkyl group" means - in itself or in moieties, for instance in alkoxy groups - straight or branched chain aliphatic saturated hydro¬ carbon groups having one to four carbon atoms (such as e.g. methyl, ethyl, n-propyl and tert.-butyl group). As used herein the term "Cg_*]_o aryl group" means phenyl group or naphthyl group, optionally bearing a C*L_4 alkyl group.
The present invention also relates to a process for the preparation of compounds of general formula (I) and the geometric isomers, tautomers and hydrates thereof which comprises a) reacting a 3-cyano-4H-pyrido[l,2-a]pyrimidine-4- -imine of general formula (III)
(wherein R, R1 and R2 are the same as defined above) with an alkali azide, in the presence of ammonium chloride and solvent, at a temperature between 0 and 150 °C, or b) reacting a compound of general formula (IV)
R1
R2C(OR )3 (VI)
(wherein R2 is the same as defined above and R3 represents 0^-4 alkyl) and with 2-(lH-tetrazol-5- -yl)-acetonitrile in the presence of an acidic anhydride and Lewis acid, or d) reacting a 2-amino-pyridine of general formula (V) (wherein R and R1 are the same as defined above) with a compound of general formula (VII)
HfVN
(wherein R2 and R3 are the same as defined above) . For alkali azide preferably sodium azide is used.
If desired, dipolar aprotic solvents (e.g. dimethyl- formamide) may preferably be used.
The resulting compound of the general formula (I) (wherein R, R1 and R2 are the same as above) precipitates from the reaction mixture immediately, or after pouring
the reaction mixture onto another solvent mixture. The product may be obtained from the reaction mixture by filtration, or after evaporation of the solvent by e.g. distillation. The compounds of the general formula (I) (wherein R, R1 and R2 are the same as above) thus obtained may be purified by the usual methods (such as for instance re- crystallisation or chromatography) .
The starting materials of general formulae (III) and (IV) (wherein R, R1 and R2 are the same as defined above) are known from the literature (Journal of Organic Chemistry, 1986, 5_1, 2988), or they may be prepared in an analogous way. The starting materials of general formulae (V) and (VI) (wherein R, R1, R2 and R3 are the same as defined above) are available on the market, whereas the compound of general formula (VII) (wherein R2 and R3 are the same as defined above) may be prepared by analogy of the known alkoxymethylenemalonitriles.
The invention is illustrated in details by the following non-limiting Examples.
Examples
Example l
18.98 g (0.1115 mol) of 4-imino-4H-pyrido[l,2-a]- pyrimidine-3-carbonitrile, 7.25 g (0.1115 mol) of sodium azide and 6.0 g (0.1115 mol) of ammonium chloride are stirred in 100 ml of dimethylformamide at 80 °C for 1 hour. The warm reaction mixture is poured onto 300 ml of ice-water mixture and the pH is adjusted to pH = 3 with the help of 10 % hydrochloric acid solution (35 ml) . The precipitate is filtered off, washed with water. Product: 21.34 g (89.8 %) 3-(2-pyridylamino)-2-(lH- -tetrazol-5-yl)-acrylnitrile.
Mp.: 294-295 °C (ethanol-water)
Analysis for C9H7N7 calculated: C 50.70 %; H 3.31 ϊ; N 45,99 I; found: C 50.92.%; H 3.18 ; N 46.09 %.
Example 2
46.05 g (0.25 mol) of 9-methyl-4-imino-4H-pyrido-
[l,2-a]pyrimidine-3-carbonitrile, 16.25 g (0.25 mol) of sodium azide and 13.37 g (0.25 mol) of ammonium chloride are stirred in 250 ml of dimethylformamide at 80 °C for 1 hour. The reaction mixture is cooled to 30 °C and poured onto 750 ml of ice-water mixture and the pH is adjusted to pH = 5-6 with the help of 96 % acetic acid (17 ml) .
The precipitate is filtered off, washed with water. Product: 51.2 g (90.1 %) of 3-[ (3-methyl-2-pyridyl)-
-amino]-2-(lH-tetrazol-5-yl)acrylnitrile, which contains
1.25 ml crystal water.
Mp: 322 ,°C decomp.
Analysis for C10H9N7 • 1.25 H 0 calculated: C 48.10 I; H 4.64 -I; N 39.26 I; found: C 48.37 %; H 4.55 %; N 39.65 %.
Example 3
18.4 g (0.1 mol) of {[ (6-methy1-2-pyridyl)-amino]- -methylene}-propanedinitrile, 6.5 g (0.1 mol) of sodium azide and 5.4 g (0.1 mol) of ammonium cloride are stirred in 100 ml of dimethylformamide at 80 °C for 1 hour. The reaction mixture is poured onto 350 ml of water and the pH is adjusted to pH = 3 with the help of 10 % hydro- chloric acid solution (20 ml) . The precipitate is filtered off, washed with water.
Product: 20.92 g (92.2 %) of 3-[ (6-methy1-2-pyridyl)- -amino]-2-(lH-tetreazol-5-yl)-acrylnitrile. Mp. : 251 °C decomp.
Analysis for C- QU^H calculated: C 52.86 %; H 3.99 %; N 43.15 %; found: C 52.86 ; H 3.87 I; N 42.46 %.
Example 4
6.26 g (0.0316 mol) of {l-[ (6-methyl-2-pyridyl)- -amino]-ethylidene}-propane-dinitrile, 2.10 g (0.0316 mol) of sodium azide and 1.71 g (0.0316 mol) of ammonium chloride are stirred in 35 ml of dimethylformamide at 80 °C for 3 hours. The reaction mixture is poured onto 100 ml of water and cooled in refrigerator. The precipitated crystals are filtered off, washed with water. Product: 4.65 g (61.0 %) of 3-methyl-3-[ (6-methyl-2- -pyridyl)-amino]-2-(lH-tetrazol-5-yl)acrylnitrile. Mp: 238-240 °C decomp. (dimethylformamide) Analysis for CnH-n-lj calculated: C 54.76 %; H 4.60 I; N 40.64 %; found: C 54.20 %; H 4.88 %; N 40.21 %.
Example 5
15.1 g (0.074 mol) of 7-chloro-4-imino-4H-pyrido- [l,2-a]pyrimidine-3-carbonitrile, 4.81 g (0.074 mol) of sodium azide and 3.95 g (0.074 mol) of ammonium chloride are stirred in 75 ml of dimethylformamide at 100 °C for 1.5 hours. The reaction mixture is poured onto 225 ml of water and cooled in refrigerator. The precipitated crystals are filtered off, washed with water. Product: 12.13 g (66.2 %) of 3-[ (5-chloro-2-pyridyl)- -amino]-2-(lH-tetrazol-5-yl)-acrylnitrile. Mp: 318-320 °C (50 % aqueous ethanol)
Analysis for C9H6N7C1 • 3H20 calculated: C 35.80 %; H 4.00 %; N 32.50 %; Cl 11.77 %; found: C 35.26 %; H 3.60 %; N 32.05 %; Cl 11.63 %.
Example 6
5.53 g (0.03 mol) of 7-methyl-4-imino-4H-pyrido- [1, 2-a]pyrimidine-3-carbonitrile, 1.95 g (0.03 mol) of sodium azide and 1.6 g (0.30 mol) of ammonium chloride are stirred in 60 ml of dimethylformamide at 100 °C for 1 hour. The reaction mixture is cooled to room tempera¬ ture, poured onto 180 ml of water and the pH is adjusted to pH - 2-3 with the help of 20 % hydrochloric acid solu¬ tion. The precipitate is filtered off, washed with water. Product: 5.46 g (80.1 %) of 3-[ (5~methyl-2-pyridyl) - -amino]-2-(lH-tetrazol-5-yl) -acrylnitrile. Mp. : 307 °C decomp. Analysis for C-^ HgN calculated: C 52.86 %; H 3.99 %; N 43.15 %; found: C 52.57 %; H 3.90 %; N 43.20 %.
Example 7
5.53 g (0.03 mol) of 8-methyl-4-imino-4H-pyrido- [l,2-a]pyrimidine-3-carbonitrile, 1.95 g (0.03 mol) of sodium azide and 1.6 g (0.03 mol) of ammonium chloride are stirred in 60 ml of dimethylformamide at 100 °C for 2 hours. The reaction mixture is cooled to room tem¬ perature, poured onto 180 ml of water and the pH is adjusted to pH = 3-4 with the help of 20 % hydrochloric acid solution. The precipitate is filtered off, washed with water.
Product: 5.97 g (87.5 %) of 3-[ (4-methyl-2-pyridyl) - -amino]-2-(lH-tetrazol-5-yl) -acrylnitrile. Mp: 289-290 °C decomp. (dimethylformamide) Analysis for C**LOH9N7 calculated: C 52.86 %; H 3.99 ; N 43.15 %; found: C 52.96 %; H 3.95 I; N 43.37 %.
Example 8 5.95 (0.03 mol) of {[ (4 ,6-dimethy1-2-pyridyl)-
-amino]-methylene}-propanedinitrile, 1.05 g (0.03 mol) of sodium azide and 1.6 g (0.03 mol) of ammonium chloride are stirred in 60 ml of dimethylformamide at 100 °C for 3 hours. The reaction mixture is cooled to 60 °C, poured onto 180 ml of water and the pH is adjusted to pH = 5 with 10 % hydrochloric acid solution (10 ml) . The precipitate is filtered off, washed with water. Product: 6.47 g (89.4 %) of 3-[ (4,6-dimethyl-2-pyridyl)- -amino]-2-(lH-tetrazol-5-yl)-acrylnitrile semi-hydrate. Mp: 238-239 °C decomp.
Analysis for C11H11N7'l/2 H20 calculated: C 52.79 I; H 4.83 I; N 39.18 %; found: C 52.65 %; H 4.83 %; N 39.15 %.
Example 9
5.58 g (0.03 mol) of 9-hydroxy-4-imino-4H-pyrido- [l,2-a]pyrimidine-3-carbonitrile, 1.95 g (0.03 mol) of sodium azide and 1.6 g (0.03 mol) of ammonium chloride are stirred "in 60 ml of dimethylformamide at 100 °C for 3 hours. The reaction mixture is cooled to room tempera¬ ture, poured onto 180 ml of water and the pH is adjusted to pH = 3 with 10 % hydrochloric acid solution (13 ml) . The precipitate is filtered off, washed with water. Product: 6,52 g (94.9 %) of 3-[ (3-hydroxy-2-pyridyl)- -amino]-2-(lH-tetrazol-5-yl)-acrylnitrile. Mp: 258-259 °C decomp. Analysis for C9H7N7-l/3 H20 calculated: C 45.96 %; H 3.28 I; N 41.68 ; found: C 45.97 %; H .003 %; N 42.17 %.
Example 10
2.76 g (0.01 mol) of 9-benzyloxy-4-amino-4H-pyrido- [l,2-a]pyrimidine-3-carbonitrile, 0.65 g (0.01 mol) of sodium azide and 0.53 g (0.01 mol) of ammonium chloride are stirred in 20 ml of dimethylformamide at 100 °C for 1
hour. The reaction mixture is cooled to room temperature, poured onto 60 ml of water and the pH is adjusted to pH = 3 with 10 % hydrochloric acid solution (5 ml) . The pre¬ cipitate is filtered off, washed with water. Product: 2.77 g (87 %) of 3-[ (3-benzyloxy-2-pyridyl)- -amino]-2-(lH-tetrazol-5-yl)-acrylnitrile. Mp: 246-248 °C decomp. Analysis for C^gH^^O calculated: C 60.20 %; H 4.10 I; N 30.72 %; found: C 60.14 %; H 4.10 I; N 31.04 %.
Example 11
4.35 g (0.015 mol) of 9-benzyloxy-2-methyl-4-imino- -4H-pyido[l,2-a]pyrimidine-3-carbonitrile, 0.975 g (0.015 mol) of sodium azide and 0.8 g (0.015 mol) of ammonium chloride are stirred in 30 ml of dimethylformamide at 100 °C for 1 hour. The reaction mixture is cooled to room temperature, poured onto 90 ml of water and the pH is adjusted with 3 ml of 10 % hydrochloric acid. The pre- cipitate is filtered off, washed with water.
Product: 2.75 g (55 %) of 3-methyl-[ (3-benzyloxy-2- -pyridyl)-amino]-2-(lH-tetrazol-5-yl)-acrylnitrile. Mp: 275 °C decomp. Analysis for C17H15N7O calculated: C 61.25 I; H 4.54 %; N '29.41 %; found: C 61.39 ; H 4.39 %; N 29.94 %.
Example 12
1.2 g (5 mmol) of 7,9-dichloro-4-imino-4H-pyrido- [i,2-a]pyrimidine-3-carbonitrile, 0.35 g (5.4 mmol) of sodium azide and 0.3 g (5.6 mmol) of ammonium chloride are stirred in 18 ml of dimethylformamide at 100 °C for 1 hour. The reaction mixture is cooled to room temperature and poured onto 40 ml of water. The pH is adjusted to pH = 5 with 5 % hydrochloric acid (30 ml). The"precipitated
crystals are filtered off, washed with water. Product: 1.25 g (88.65 %) of 3-[ (3,5-dichloro-2-pyridyl)- -amino]-2-(lH-tetrazol-5-yl)-acrylnitrile. Mp: 188 °C decomp. Analysis for C9H5N7CI2 calculated: C 38.32 %; H 1.79 %; N 34.75 %; Cl 25.14 %; found: C 38.45 %; H 1.97 %; N 34.25 %; Cl 24.92 %.
Example 13 2.5 g (0.01 mol) of 7-bromo-4-imino-4H-pyrido-
[l,2-a]pyrimidine-3-carbonitrile, 0.65 g (0.01 mol) of sodium azide and 0.55 g (0.01 mol) of ammonium chloride are stirred in 20 ml of dimethylformamide at 80 °C for 1.5 hours. The reaction mixture is cooled to room temperature and poured onto 60 ml of water. The pH is adjusted to pH = 2 with the help of 5 % hydrochloric acid solution (15 ml) . The precipitate is filtered off, washed with water. Product: 2.67 g (91.44 %) of 3-[ (5-bromo-2-pyridyl)- -amino]-2-(lH-tetrazol-5-yl)-acrylnitrile. Mp: 253-255 °C decomp. (dimethylformamide) Analysis for CgH -^Br calculated: C 37.00 %; H 2.07 %; N 33.57 %; Br 27.36 %; found: C 37.07 %; H 2.07 %; N 33.77 %; Br 27.13 %.
Example 14
2.6 g (0.01 mol) of l-[ (6-methy1-2-pyridyl)-amino]- -benzylidene propanedinitrile, 0.65 g (0.01 mol) of sodium azide and 0.54 g (0.01 mol) of ammonium chloride are stirred in 20 ml of dimethylformamide at 80 °C for 3 hours. The reaction mixture is cooled to room temperature and poured onto 60 ml of water. The precipitated crystals are filtered off, washed with water. Product: 2.08 g (68.65 %) of 3-phenyl-[ (6-methy1-benzyl- oxy-2-pyridyl)-amino]-2-(lH-tetrazol-5-yl)-acrylnitrile.
Analysis for C16H-]_3N7 calculated: C 63.36 %; H 4.32 %; N 32.32 found: C 63.11 %; H 3.93 %; N 32.38
Example 15
1.55 g (0.007 mol) of 9-nitro-4-imino-4H-pyrido- [l,2-a]pyrimidine-3-carbonitrile, 0.98 g (0.015 mol) of sodium azide and 0.8 g (0.015 mol) of ammonium chloride are stirred in 50 ml of dimethylformamide at 100 °C for 2 hours. The reaction mixture is cooled to room temperature and poured onto 150 ml of water and on addition of a few drops of 10 % hydrochloric acid the product precipitates. It is filtered off, washed with water. Product: 0.89 g (49.2 %) of 3-[ (3-nitro-2-pyridyl)- -amino]-2-(lH-tetrazol-5-yl)-acrylnitrile. Mp: 238 °C decomp. Analysis for CgHgNg02 calculated: C 41.87 %; H 2.34 %," N 43.49 %; found: C 41.91 %; H 2.30 %; N 43.77 %.
Example 16
1.21 g (5 mmol) of [ (3-ethoxycarbonyl-2-pyridyl)- -amino]-methylene propanedinitrile, 0.32 g (5 mmol) of sodium azide and 0.27 g (5 mmol) of ammonium chloride are stirred in 20 ml of dimethylformamide at 100 °C for 2 hours. The reaction mixture is cooled to room tempera¬ ture, poured onto 50 ml of water and the pH is adjusted to pH = 5 with 5 % hydrochloric acid solution (20 ml) . The precipitate is filtered off, washed with water. Product: 1.04 g (72.73 %) of 3-[ (3-ethoxycarbonyl-2- -pyridyl)-amino]-2-(lH-tetrazol-5-yl)-acrylnitrile. Mp: 210 °C decomp. (ethanol) Analysis for *-L Hι*-LN7θ2 calculated: C 50.53 1; H 3.89 %; N 34.37 %; found: C 50.18 %; H 3.79 %; N 34.03 %.
Claims
1. Compound of the general formula (I)
R stands for hydrogen, ^-4 alkyl, halogen, hydroxy, nitro, carboxy, C _5 alkoxycarbonyl or C7-12 aralkoxy;
R1 stands for hydrogen, C*-__4 alkyl or halogen;
R2 represents hydrogen, C^_4 alkyl or C _^o aryl.
2. Process for the preparation of a compound of the general formula (I)
or geometric isomers, tautomers and hydrates thereof, wherein
R stands for hydrogen, C^-4 alkyl, halogen, hydroxy, nitro, carboxy, C2-5 alkoxycarbonyl or c7-12 aralkoxy;
R1 stands for hydrogen, ^-4 alkyl or halogen;
R2 represents hydrogen, Cι_4 alkyl or Cg_10 aryl - which c o m p r i s e s a) reacting a 3-cyano-4H-pyrido[l,2-a]pyrimidine-4- -imine of general formula (III)
- wherein R, R1 and R2 are the same as defined in Claim 1 - with an alkali azide, in the presence of ammonium chloride, or b)
- wherein R and R1 are as defined in claim 1 - with an orthoester of general formula (VI)
R C(OR3)3 (VI)
- wherein R2 is the same as defined in claim 1 and R3 represents C^_4 alkyl - and with 2-(lH-tetrazol- -5-yl)-acetonitrile, or d) reacting a 2-amino-pyridine of general formula (V)
- wherein R and R1 are the same as defined in claim 1 - with a compound of general formula (VII) R2 CN
\ /
C = C
*N (VII)
R30
HN ,H
- wherein R2 is defined in claim 1 and R3 is as defined in process c.
3. A process according to claim 2a or 2b which c o m p r i s e s using sodium azide as alkali azide.
4. A process according to claim 2a or 2b which c o m p r i s e s carrying out the reaction in the presence of a solvent.
5. A process according to claim 4 which c o m p r i s e s using dimethylformamide as solvent.
6. A process according to claim 2a or 2b which c o m p r i s e s carrying out the reaction at a temperature betweeen 0 and 150 °C.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU9200431A HUT63406A (en) | 1992-02-13 | 1992-02-13 | Process for producing tetrazolylacryl nitrile derivatives |
| HUP9200431 | 1992-02-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1993016070A1 true WO1993016070A1 (en) | 1993-08-19 |
Family
ID=10981334
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/HU1993/000008 WO1993016070A1 (en) | 1992-02-13 | 1993-02-12 | 3-(pyridylamino)-2-(1h^_-tetrazol-5-yl)-acrylnitriles and a process for the preparation thereof |
Country Status (7)
| Country | Link |
|---|---|
| CN (1) | CN1082037A (en) |
| AU (1) | AU3573693A (en) |
| HU (1) | HUT63406A (en) |
| IL (1) | IL104707A0 (en) |
| MX (1) | MX9300778A (en) |
| SI (1) | SI9300074A (en) |
| WO (1) | WO1993016070A1 (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4474953A (en) * | 1982-09-09 | 1984-10-02 | Riker Laboratories, Inc. | Process and intermediates for the preparation of 3(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-ones |
| EP0385634A2 (en) * | 1989-02-27 | 1990-09-05 | Wako Pure Chemical Industries Ltd | Process for producing pyrido[1,2-a] pyrimidine derivative |
-
1992
- 1992-02-13 HU HU9200431A patent/HUT63406A/en unknown
-
1993
- 1993-02-12 IL IL104707A patent/IL104707A0/en unknown
- 1993-02-12 AU AU35736/93A patent/AU3573693A/en not_active Withdrawn
- 1993-02-12 WO PCT/HU1993/000008 patent/WO1993016070A1/en active Application Filing
- 1993-02-12 SI SI19939300074A patent/SI9300074A/en unknown
- 1993-02-12 MX MX9300778A patent/MX9300778A/en unknown
- 1993-02-13 CN CN93102961.9A patent/CN1082037A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4474953A (en) * | 1982-09-09 | 1984-10-02 | Riker Laboratories, Inc. | Process and intermediates for the preparation of 3(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-ones |
| EP0385634A2 (en) * | 1989-02-27 | 1990-09-05 | Wako Pure Chemical Industries Ltd | Process for producing pyrido[1,2-a] pyrimidine derivative |
Non-Patent Citations (1)
| Title |
|---|
| CHEMICAL ABSTRACTS, Volume 115, No. 11, issued 16 September 1991, (Columbus, Ohio, U.S.A.), AMANO et al., "Preparation of Pyrido(1,2-A)Pyrimidine Derivatives", page 906, Column 2, Abstract No. 114 538e; & JP,A,03 074 385, (TOKYO TANABE CO). * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU3573693A (en) | 1993-09-03 |
| SI9300074A (en) | 1993-09-30 |
| IL104707A0 (en) | 1993-06-10 |
| MX9300778A (en) | 1993-09-30 |
| HU9200431D0 (en) | 1992-04-28 |
| CN1082037A (en) | 1994-02-16 |
| HUT63406A (en) | 1993-08-30 |
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