JPS58428B2 - Synquina 2-oxo-1,2,3,4-tetrahydropyrido (2,3-D) Pyrimidine - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to compounds of the general formula (I) in which R1 is substituted with (1) a phenyl group, (2) a halogen atom, a lower alkyl group, a lower alkoxy group, a nitro group or a trifluoromethyl group; R2 is (1) a lower alkyl group, (2) a lower alkyl group substituted with a halogen atom, a lower cycloalkyl group, a hydroxyl group, an alkoxy group, an amino group, or a phenyl group, (3) an alkynyl group, ( The present invention relates to a method for producing a novel 2-oxo-1,2,3,4-tetrahydropyrido [2,3-d)pyrimidine derivative represented by 4) (meaning an alkenyl group).

More specifically, the compound represented by the general formula (II) (wherein R1 has the same meaning as above) is combined with the general formula (1) % formula % (1) (wherein R2 has the same meaning as above, refers to a halogen atom and an organic sulfonyloxy group) to produce a compound represented by the general formula (I).

To explain R1 and R2 in the general formulas (I), (II) and (III) in more detail, R1 is a phenyl group or a halogen atom such as chlorine, bromine, fluorine, iodine, etc., methyl, ethyl, propyl, etc. Lower alkyl groups, lower alkoxy groups such as methoxy, ethoxy, propoxy,
A phenyl group substituted with 1 to 2 substituents such as a nitro group and a trifluoromethyl group at any position.The lower alkyl group of R2 is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, n-pentyl. Substituted lower alkyl groups include chlorine 1. Bromine, fluorine,
A halogen atom such as iodine, a lower cycloalkyl group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, a lower alkyl group substituted with a hydroxyl group, an alkoxy group, an acetoxy group, an amino group or a phenyl group, an alkynyl group such as propargyl, The alkenyl group is allyl,
Represents 3-methylallyl, etc.

In addition, organic sulfonyloxy groups include arylsulfonyloxy groups (e.g., benzenesulfonyloxy, p-toluenesulfonyloxy, p-nitrobenzenesulfonyloxy, etc.), alkylsulfonyloxy groups (e.g., methylsulfonyloxy, ethylsulfonyloxy, and trifluoromethyl sulfonyloxy, etc.) and aralkylsulfonyloxy groups (eg, benzylsulfonyloxy, etc.).

The compound of general formula (I) which is the starting material of the present invention is 2-
It can be produced in good yield by reacting an amino-3-hydroxymethylpyridine derivative with urea.

The reaction formula of the present invention is as follows.

In carrying out the invention, metal compounds such as sodium amide, sodium hydride and sodium ethylate, organic bases such as pyridine, trimethylamine, etc., in organic solvents such as dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, benzene, toluene, xylene, dicrime, etc. It is preferable to carry out the reaction in the presence of an inorganic base such as alkali hydroxide, alkali carbonate, etc. In particular, when the above-mentioned metal compounds are used, the target compound can be obtained in a good yield.

Although the reaction proceeds at room temperature, it proceeds more quickly and the reaction time is shortened by heating.

The solvent of the reaction product was distilled off under reduced pressure, and the residue was dissolved in ether,
A pure product can be obtained by recrystallizing it with an organic solvent such as methanol or by separating and purifying it by column chromatography.

The compound obtained by the present invention is a new compound that has not been described in any literature, and exhibits significant pharmacological activities such as analgesic action, anti-inflammatory action, and central nervous system depressing action, and is an industrially useful compound as a pharmaceutical.

The present invention also includes converting the compounds thus obtained into addition salts with inorganic and organic acids by conventional pharmaceutically acceptable techniques.

Examples of the present invention are shown below.

Example 1 ■-(m-bromophenyl)-2-oxo-1°2.3
．． 4-tetrahydropyrido(2,3-d)pyrimidine 3
．． 0.6 g of 50% sodium hydride was added to a mixture of 0.0 g and 30 ml of dry dimethylformamide, and the mixture was stirred for 30 minutes.

3.5 g of propargyl bromide was added thereto, and after reacting at room temperature for 1 hour, the solvent was distilled off under reduced pressure, the residue was diluted with water, and the liberated oil was extracted with ethyl ether.

After dehydrating the ether layer with magnesium sulfate, it was adsorbed on an alumina column and eluted with ether to separate and purify it, resulting in colorless frism crystals of 1-(m-bromophenyl)-3-propargyl-2-oxo-1,2,3, 2.9 g of 4-tetrahydropyrido(2,3-d)pyrimidine was obtained.

The melting point and elemental analysis values of this substance were as follows.

Melting point 118-119°C Elemental analysis value C16H12ON3Br Theoretical value C: 56. OI H: 3.54 N: 12.28
Actual value C: 56. OI H: 3.49 N: 12.24
Example 2 1-(m-trifluoromethylphenyl)-2-oxo-1,2,3,4-tetrahydropyride (2,3-d)
0.7 g of pyrimidine was dissolved in 10 ml of dimethylformamide, 0.13 g of sodium hydride was added thereto, and a mixture of 5.1 g of methyl iodide and 5 ml of dimethylformamide was gradually added dropwise under ice cooling.

Immediately after the addition, the mixture was heated in an oil bath at 100° C. for 15 hours.

After the reaction was completed, the solvent was distilled off under reduced pressure, ice water was added to the residue, and the mixture was extracted with ether.

The ether layer was washed with water, dehydrated, adsorbed on a column packed with alumina, developed with ether, and the eluate solvent was concentrated to form colorless prismatic crystals of 1-(m-trifluoromethylphenyl)-3-methyl-2-oxo. -1,2°3.4-Tetrahydropyrido C2,3-d) 0.6 g of pyrimidine was obtained.

The melting point and elemental analysis values of this substance were as follows.

Melting point 122-124℃ Elemental analysis value C15N12 F3 N30 Theoretical value C: 58.63 H: 3.94 N: 13
．． 68 actual value C: 58.52 H: 3.89 N: 13
．． 61 Example 3 1-Phenyl-2-oxo-1,2,3,4-tetrahydropyrido [2,3-d) 1.2 g of sodium hydride in a mixture of 4.5 g of pyrimidine and 50 ml of dry dimethylformamide was added and stirred at room temperature for 30 minutes, and the temperature was further raised to 90 to 100°C. 12.8 g of p-toluenesulfonic acid isopropyl ester was gradually added dropwise thereto, and after reacting for 1 hour, the solvent was removed under reduced pressure. After distillation, water was added to the residue and the precipitated crystals were counted.

When the compound was dissolved in ethyl ether, adsorbed on a column packed with alumina, and eluted with ethyl ether to separate and purify it, colorless prismatic crystals of 1-phenyl-3-isopropyl-2-oxo-1,2,3,4- Tetrahydropyride C
4.1 g of 2,3-d) pyrimidine were obtained.

The melting point and elemental analysis values of this substance were as follows.

Melting point 164-165℃ Elemental analysis value C16H17N30 Theoretical value C near 1.88 H: 6.41 N: 15.72
Actual value C near 1.75 H: 6.41 N: 15.72
Examples 4 to 1.09 The compounds shown in the following table were synthesized in good yields according to the methods of Examples 1 to 3.

Claims (1)

[Claims] 1 General formula (wherein R1 means (1) a phenyl group, (2) a phenyl group substituted with a halogen atom, a lower alkyl group, a lower alkoxy group, a nitro group, or a trifluoromethyl group) ) is a compound represented by the general formula (wherein R2 is a lower alkyl group substituted with (1) a lower alkyl group, (2) a halogen atom, a lower cycloalkyl group, a hydroxyl group, an alkoxy group, an acetoxy group, an amino group, or a phenyl group). A general formula characterized by reacting an alkyl group, (3) an alkynyl group, or (4) an alkenyl group with a compound represented by has the same meaning as above).