JPS58433B2 - Cinquinapiride -14- Diazepinedione Yudotaino Seizouhou - Google Patents

Description

Detailed Description of the Invention The present invention is based on the general formula (I) (wherein R1 is a phenyl group, a halogen atom, or a phenyl group substituted with a trifluoromethyl group, R2 is a hydrogen atom,
The present invention relates to a method for producing a novel pyrido-1,4-diazepinedione derivative represented by a lower alkyl group, or a lower alkyl group substituted with a halogen atom or a lower cycloalkyl group.

More specifically, it relates to a method for producing a compound represented by the general formula (I) by oxidizing a compound represented by the general formula (n) (wherein R and R have the same meanings as above).

To explain R1 and R2 in the general formulas (I) and (1) in more detail, R1 is a phenyl group, a halogen atom such as chlorine, bromine, fluorine, or iodine, or a trifluoromethyl group at the position of 1. ~2 substituted phenyl groups,
The lower alkyl group of R is a lower alkyl group such as methyl, ethyl, propyl, or isopropyl, and the substituted lower alkyl group is a lower alkyl group substituted with a halogen atom such as chlorine, bromine, or fluorine, or a lower cycloalkyl group such as cyclopyl or cyclobutyl. Represents an alkyl group.

The compound represented by the general formula (n), which is the starting material of the present invention, can be obtained in good yield by reacting a 2-anilino-3-aminomethylpyridine derivative with a reactive derivative of monohalogenacetic acid.

The reaction formula of the present invention is as follows.

In carrying out the present invention, the general formula (I
This is carried out by reacting the compound f) with an oxidizing agent.

Oxidizing agents used include potassium permanganate, manganese dioxide, chromium trioxide, potassium dichromate, sodium dichromate, sodium ferricyanide, selenium dioxide, hydrogen peroxide, lead tetraacetate, or mercuric acetate. can be mentioned.

Further, the solvent used is appropriately selected from inert solvents such as water, acetone, tetrahydrofuran, dioxane, pyridine, glacial acetic acid, sulfuric acid, and nitric acid.

The reaction is carried out at room temperature or by heating; heating shortens the reaction time.

The compound obtained by the method of the present invention is a new compound that has not been described in any literature, and has anti-inflammatory and central nervous system depressing effects, such as analgesic, muscle relaxant, anti-spasmodic and hypnotic effects, and is industrially available as a pharmaceutical. It is a very useful compound.

Furthermore, the present invention uses the compound thus obtained by adding hydrochloric acid, hydrobromic acid, sulfuric acid,
It also includes the production of inorganic and organic acid salts such as phosphoric acid, acetic acid, citric acid, fumaric acid, and maleic acid.

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

Example 1 1 (m-trifluoromethylphenyl)-4-ethyl-1,3,4,5-tetrahydro-3-oxo-2
H-pyrido[2,3-e][1,4]diazepine 1.0
After dissolving g in 12 ml of acetic acid, Na2Cr207 ・2H
700.89g was added and stirred at 70°C for 2 hours.

After the reaction was completed, the solvent was distilled off under reduced pressure, and ice water was added to the residue to obtain crude crystals.

This was recrystallized from a mixed solvent of ether and petroleum ether to form colorless needle-like crystals of 1-(m-trifluoromethylphenyl)-4-ethyl-1,3,4,5-tetrahydro-3.
,5-dioxo-2H-pyrido(2,3-e)[1,4
] 730 mg of diazepine was obtained.

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

Melting point 190-191°C Elemental analysis value C1□H14F3N30□ Theoretical value C: 58.45 H: 4. OI N:12.03
Actual value C2 58.39 H: 3.98 N: 12.12
Example 2 l-(0-fluorophenyl)-4-(2,2,2-
trifluoroethyl) -1,3,4,5-tetrahydro-3-oxo-2H-pyrido(2,3-e) (L4)
After dissolving 3.4 g of diazepine in 20 m7 of glacial acetic acid, 3 g of chromic anhydride was added and the mixture was refluxed on an oil bath for 2 hours.

After the reaction, the solvent was distilled off under reduced pressure, and ice water was added to the residue to obtain crude crystals.

This product was recrystallized from a mixed solvent of acetone and petroleum ether to form colorless needle-shaped crystals of 1-(0-fluorophenyl)-4.
-(2,2,2-trifluorotyl)-1,3,4,5
-tetrahydro-3,5-dioxo-2H-pyrido [2
, 3-e) 1.8 g of (1,4) diazepine was obtained.

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

Melting point 207-208°C Elemental analysis value C16H11F4N302 Theoretical value C: 54.40 H: 3.14 N: 11.89
Actual value C: 54.51 H: 3.19 N: 11.80
Example 3 l-(0-chlorophenyl)-4-cyclopropylmethyl-1,3,4,5-tetrahydro-3-oxo-2H
-pyrido(2,3-e)(1,4]diazepine 3.3g
was dissolved in 30 ml of acetic acid, 2078.8 g of K2Cr was added, and the mixture was heated at 70°C for 2 hours.

After the reaction was completed, the solvent was distilled off under reduced pressure, and ice water was added to the residue to obtain crude crystals.

This was recrystallized from an ether-petroleum ether mixed solvent to give colorless needle-like crystals of 1-(O-chlorophenyl)-4-cyclopropylmethyl-1,3,4,5-tetrahydro-3
．． 5-dioxo-2H-pyrido[2,3-e)[1,4
] 2.0 g of diazepine was obtained.

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

Melting point 253-255°G Elemental analysis value Cl8H16CIN302 Theoretical value C: 63.25 H: 4.72 N: 12.29
Actual value C: 63.30 H: 4.67 N: 12.27
The following compounds were synthesized according to the methods of Examples 1 to 3.

1-(m trifluoromethylphenyl)-4-methyl-1,3,4,5-tetrahydro-3,5-dioxo-2H-pyrido[2,3-e][1,4]diazepine Melting point 212~ 214°C 1-phenyl-4-methyl-1,3,4,5-tetrahydro-3,5-dioxo-2H-pyrido (2,3-e)
[1,4]Diazepine Melting point 260-261°C 1-phenyl-4-ethyl-1,3,4,5-tetrahydro-3,5-dioxo-2H-pyrido (2,3-e)
[1,4]Diazepine Melting point 207-209°C 1-(0-chlorophenyl)-4-methyl-1°3,4
．． 5-tetrahydro-3,5-dioxo-2H-pyrido(2,3-e)(1,4-)diazepine melting point
240-241°C 1-(0-chlorophenyl)-4-ethyl-1°3,4
．． 5-tetrahydro-3,5-dioxo-2H-pyrido (2,3-e) [I1,4) diazepine melt
Point 206-207°C ■-(0-fluorophenyl)-4-methyl-1,3,
4,5-tetrahydro-3,5-dioxo-2H-pyrido(2,3-e) C1,4) diazepine melting point
202~203°C

Claims (1)

[Claims] 1 General formula (wherein W is a phenyl group, a halogen atom, or a phenyl group substituted with a trifluoromethyl group, and R2 is a hydrogen atom, a lower alkyl group, or a halogen atom or a lower cycloalkyl group) A novel pyrido-1,4-di compound represented by the general formula (in which R and R have the same meanings as above), which is characterized by oxidizing a compound represented by a substituted lower alkyl group. Method for producing azepinedione derivatives.