JPS5813551B2 - Sinquinapiride (4,3-D) Pyrimidinedione - Google Patents

Description

Detailed Description of the Invention The present invention is based on the general formula (1) (wherein R is (1) a lower alkyl group, (2) a halogen atom, a lower cycloalkyl group, a lower alkoxy group, or a substituted or unsubstituted phenyl group). A novel pyrido[4,3-d]pyrimidine-2. The present invention relates to a method for producing a 4(IH,3H) monodione derivative.

More specifically, the general formula (II) (wherein, A lower alkylamino group substituted with a nyl group, (4) an alkenyl group or an amine group substituted with an alkynyl group) is added to a compound represented by the general formula (IID (wherein, R has the same meaning as above). The present invention relates to a method for producing a compound represented by the general formula (I) by reacting isocyanates represented by the formula (I).

To explain in more detail about X and H in the above general formulas (I), (II) and (I[I), the lower alkoxy group of X is a lower alkoxy group such as methoxy or ethoxy, and the lower alkoxy group of R and The alkyl group is a lower alkyl group such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, etc., and the substituted lower alkyl group is a lower alkyl group substituted with a halogen atom, lower cycloalkyl group, alkoxy group, aryl group, etc. The unsaturated alkyl group represents an alkenyl group such as allyl and an alkynyl group such as propargyl.

The compound represented by the general formula (II), which is the starting material of the present invention, can be obtained by reacting 4-(m-1-lifluoromethylanilino)nicotinic acid and its reactive derivatives with the corresponding alcohols and amines. Good yield is obtained.

The reaction formula of the present invention is as follows.

The above reaction formula corresponds to the reaction in the presence of metal compounds such as sodium alcoholate, sodium hydride, potassium hydride, sodium amide, etc. in an inert organic solvent such as tetrahydrofuran, diglyme, dioxane, benzene, dimethylformamide, etc. This is done by reacting incyanate.

The reaction temperature is not particularly limited and may proceed at room temperature, but it is preferably carried out at or near the boiling point of the solvent used.

A pure product can be obtained from the reaction product by distilling off the solvent under reduced pressure and recrystallizing the residue from an organic solvent such as methanol or ether, or by separating and purifying it by column chromatography.

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

EXAMPLES The present invention will be explained in more detail with reference to Examples below.

Example 1 3.0 g of 4-(m-t'J fluoromethylanilino)nicotinic acid methyl ester was dissolved in 20 m of tetrahydrofuran.
0.6 g of about 50% sodium hydride was added, and the mixture was stirred at room temperature for 15 minutes.

Next, a solution of 2.4 g of allyl isocyanate and 10 WL of tetrahydrofuran was added under cooling, and the mixture was reacted for 1 hour at room temperature and then for 3 hours under reflux.

After the reaction, the solvent was distilled off under reduced pressure, water was added to the residue, and the precipitated crystals were recrystallized from ether to give colorless prism crystals of 1-(m-trifluoromethylphenyl)-3-7'.
lJ Lupirido (4.3-d) Pyrimidine-2,4 (I
2.5 g of H,3H) monodione were obtained.

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

? Point 180-181°C Elemental analysis value CI7F■lF3N30 Theoretical value C: 58.79 H: 3.49 N: 1210 Actual value C: 58.67 H: 3.42 N: 1213 Example 2 4 - (+η- After dissolving 31 g of trifluoromethylanilino)nicotinic acid ethylamide in 20 ml of diglyme, approximately 50% sodium hydride was added. Og was added and the mixture was stirred at room temperature for 15 minutes.

Next, a solution of 21 g of ethyl isocyanate and 10 ml of diglyme was added under cooling, and after stirring at room temperature for 1 hour, the mixture was reacted under reflux for 2 hours.

After the reaction, the solvent was distilled off under reduced pressure, water was added to the residue, extracted with ether, dehydrated, and concentrated to obtain colorless prism crystals.
-(m-trifluoromethylphenyl)-3-ethylpyrido(4.3-d)pyrimidine-2.4(IH,3H)
2.2 g of dione was obtained.

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

Melting point 144-145°C Elemental analysis value C16Hl2F3N30.

Theoretical value C: 57.31 H: 3.61 N: 12.53
Actual value C: 57.23 H: 3.57 N: 1248 Example 3 3.4 g of 4-(m-trifluoromethylanilino)nicotinic acid 101 butylamide was added to 20 m of tetrahydrofuran.
1, add 0.8 g of sodium amide and stir at room temperature.
Stir for 5 minutes.

Next, a solution of 1.7 g of methyl isocyanate and 10 ml of tetrahydrofuran was added under cooling, and after stirring at room temperature for 30 minutes, the mixture was reacted under reflux for 3 hours.

After the reaction, the solvent was distilled off under reduced pressure, water was added to the residue, and the precipitated crystals were recrystallized from a mixed solvent of methanol and ether to obtain colorless prismatic crystals of 1-(m-trifluoromethylphenyl)- 3-Methylpyrido[4,3-d)pyrimidine-2. 2.1 g of 4(IH,3H)-dione was obtained.

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

Melting point 178-180°C Elemental analysis value C1, H1oF3N30 Theoretical value C: 56.08 H: 3.14 N: 13.08
Actual value C: 56.01 H: 318 N: 13.11 Examples 4 to 11 According to the method of Examples 1 to 3, the compounds shown in the following table were obtained in good yields.

Claims (1)

[Claims] 1 General formula (wherein X is (1) a lower alkoxy group, (2) a lower alkylamino group, (3) a halogen atom, a lower cycloalkyl group, a lower alkoxy group, or a substituted or unsubstituted A compound represented by the general formula (wherein R is (1) a lower alkyl group, (2) A compound represented by a halogen atom, a lower cycloalkyl group, a lower alkoxy group, a lower alkyl group substituted with a substituted or unsubstituted alkoxy group, (3) an alkenyl group, or (4) an alkynyl group) is reacted. A method for producing a novel pyrido(4.3-d)pyrimidinedione derivative represented by the general formula (wherein R has the same meaning as above) characterized by the following: