JPS5812278B2 - Cinquinapiride (2,3-D) Pyrimidinedione - Google Patents

Description

Detailed Description of the Invention The present invention is based on the general formula (I) (wherein 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) phenyl group, (3) cycloalkyl group, (4) benzyl group, or (5) benzyl group substituted with a halogen atom, R2 is (1) lower alkyl group, (2) halogen atom, lower cycloalkyl A new pyrido [2.3-d) represented by a group, an alkoxy group, an acetyl group, a hydroxyl group, a lower alkyl group substituted with a phenyl group, (3) an alkenyl group, or (4) an alkynyl group)
The present invention relates to a method for producing pyrimidinedione derivatives.

More specifically, general formula (n) (wherein R1 and R2 have the same meanings as above, X represents (1) a halogen atom, (2) an inorganic acid, or (3) an ester group of an organic acid, Y (1) carbonyl group, (2) thiocarbonyl group, and (3) methylene group. It is something.

R1, R2 and X in the general formulas (I) and (n)
To explain in more detail, R1 is a phenyl group, or a halogen atom such as chlorine, bromine, fluorine, or iodine, methyl,
A phenyl group optionally substituted with 1 or 2 lower alkyl groups such as ethyl, lower narkoxy groups such as methoxy and ethoxy, nitro groups and trifluoromethyl groups, and cycloalkyl groups are cyclohexyl groups or lower alkyl-substituted cyclohexyl groups. , and a benzyl group or a benzyl group substituted with a halogen atom.

The lower alkyl group of R2 is a lower alkyl group such as methyl, ethyl, n-propyl, inglovil, n-butyl, isobutyl, pentyl, etc., and the substituted lower alkyl group is a halogen atom, lower cycloalkyl group, alkoxy group, acetyl group, or hydroxyl group. and a lower alkyl group substituted with a phenyl group, the alkenyl group is allyl, 3-methylallyl, 3 ・3
-dimethylallyl, etc., and an alkynyl group represents propargyl, etc.

Specifically, X is a halide, trifluoroacetate, sulfate (for example, CH3SO, C2H5SO4, F
SO3), sulfonates (e.g. C2H, S03, C
a H5SOa) or nitrate, etc.

The quaternary salt of general formula (n), which is the starting material of the present invention, is 1,4-dihydropyrid [2,3-d
]Pyrimidine derivative (III), 4-oxo 1,4-
Dihydropyrido[2,3-d]pyrimidine derivative (■)
, 4-thio 1,4-dihydroviride [2,3-d]pyrimidine derivative (V) or the like with an alkyl halide, an inorganic acid ester, or an organic acid ester.

To carry out the present invention, the general formula (
This is carried out by reacting the compound represented by II) with an oxidizing agent.

Examples of the oxidizing agent used include permanganate, manganese dioxide, dichromate, chromic anhydride, potassium ferricyanide, selenium dioxide, mercuric acetate, hydrogen peroxide, and ozone.

The solvent used is appropriately selected from inert solvents such as water, glacial acetic acid, sulfuric acid, nitric acid, acetone, dioxane, and alcohol.

The reaction temperature is not particularly limited, and the reaction can be carried out at room temperature or by heating, and heating shortens the reaction time.

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

Next, the present invention will be further explained with reference to Examples.

Example 1 1-(m-trifluoromethylphenyl)-3-methyl-1,4-dihydropyrido[2,3-d]pyrimidinium iodide 2.9 ml, glacial acetic acid 30 ml, chromic anhydride 3. The mixture of 01 was refluxed for 3 hours.

After the reaction is complete, the solvent is distilled off under reduced pressure, ice water is added to the residue, and the crystals that precipitate are recrystallized from methanol to obtain colorless prismatic crystals of 1-(m-trifluoromethylphenyl).
-3-methylpyrido[2.3-d]pyrimidine-2.4
2.3 g of (IH·3H) monodione was obtained.

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

Melting point 224-225℃ Elemental analysis value C15H1oF3N30 Theoretical value C: 56.08 H: 3.14 N: 13.0
8 Actual value C: 56.12 H: 3.05 N: 13.0
1 Example 2 A mixture of 3 g of 1-(m-trifluoromethylphenyl)-3-ethyl-1,4-dihydropyrido[2,3-d]pyrimidinium ethosulfate and 51 potassium dichromate was added with concentrated sulfuric acid. Add 100ml of water (1:1) and reflux for 3 minutes.
Allowed time to react.

After the reaction was completed, the reaction solution was cooled and neutralized with 10% sodium carbonate solution, and the precipitated crystals were recrystallized from methanol to obtain colorless prismatic crystals of 1-(m-trifluoromethylphenyl)-3-ethylhylide. [2.3-d) Pyrimidine-
1.8 g of 2.4 (IH.3H) dione was obtained.

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

Melting point 160-162℃ Elemental analysis value C16 H12 F3 N3 o2 Theoretical value C: 57.31 H: 3.61 N: 12.53 Actual value C: 57.21 H: 3.58 N: 12.4
9 Example 3 1-(m-fluorophenyl)-3-)thyl-4-oxo 1,4-dihydropyrido[2,3-d]pyrimidinium methosulfate 2.51 and potassium dichromate 5 100 ml of concentrated sulfuric acid/water (1:1) was added to the mixture and reacted under reflux for 3 hours.

After the reaction was completed, the reaction solution was cooled and neutralized with 10% sodium carbonate solution, and the precipitated crystals were recrystallized from methanol to obtain colorless prismatic crystals of 1-(m-fluorophenyl)-3.
-Methylhylide[2,3-d)pyrimidine-2,4(I
1.5 g of H.3H) monodione was obtained.

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

Melting point 197-198°C Elemental analysis value C14 HIO FN3 o2 theoretical value C
:61.99 H:3.72N:15.49 Actual value C:61.83 H:3.61N:15.3
8 Example 4 100 ml of glacial acetic acid was added to a mixture of 3 g of 1-(m-chlorophenyl)-3-ethyl-1-4-dihydropyrido[2.3-d]pyrimidinium ethosulfate and 5 g of potassium dichromate. The reaction was carried out 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 methanol to obtain colorless prismatic crystals of 1-(m-chlorophenyl)-3-ethylpyrid [
2.3-d] pyrimidine-2.4(IH・3H)-dione 1.5? I got it.

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

Melting point 176-177℃ Elemental analysis value C15H12CIN302 Theoretical value C: 59.71 H: 4.01 N: 13.9
3 Actual value C: 59.69 H: 4.03 N: l3.8
7 Examples 5 to 130 According to the method of Examples 1 to 4, the compounds shown in the following table were obtained in good yield.

Claims (1)

[Scope of Claims] 1 General formula (wherein R1 is (1) a phenyl group, (2) a phenyl group substituted with a halogen atom, a lower alkyl group, a lower alkoxy group, a nitro group, a trifluoromethyl group, (3) cycloalkyl group (4) benzyl group, or (5) benzyl group substituted with a halogen atom, R2 is (1) lower alkyl group, (2) halogen atom, lower cycloalkyl group, alkoxy group, acetyl , hydroxyl group, lower alkyl group substituted with phenyl group, (3) alkenyl group, or (4) alkynyl group, and X is (1) halogen atom, (2) inorganic acid, or (3) ester of organic acid. group, Y means (1) carbonyl group, (2) thiocarbonyl group, or (3) methylene group) (wherein R1 and R2 has the same meaning as above).