JPS6364427B2 - - Google Patents

Description

[Detailed description of the invention] The present invention is based on the general formula

【formula】 or

[Formula] [In the formula, R ¹ is hydrogen or lower alkyl, R ² , R ³
are the same or different hydrogen, lower alkyl,
R ⁴ represents hydrogen, lower alkyl or halogen; R ⁵ represents hydrogen or lower alkyl; R ⁶ represents hydrogen or lower alkyl. ] This invention relates to a novel benzoquinoline derivative represented by: To specifically define the symbols in the general formula [] or ['], lower alkyl refers to methyl, ethyl, propyl, butyl, etc., and halogen refers to chlorine, fluorine, bromine, etc. The compound represented by the general formula [] or ['] has platelet aggregation inhibiting action, analgesic action, etc., and is useful as a medicine. It is also useful as an intermediate for compounds having psychotropic, analgesic, antiinflammatory, and antithrombotic effects. The compound of the general formula [] or [′] is, for example, a compound of the general formula [In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ have the same meanings as above. ] The carboxylic acid represented by or its reactive derivative (e.g. acid halide) is combined with a Lewis acid (e.g.
It is produced by condensation and ring closure in the presence of sulfuric acid, polyphosphoric acid, aluminum chloride, etc.). When the condensation ring-closing reaction is a carboxylic acid in the general formula [], a general method for the condensation ring-closing reaction is applied, for example, in concentrated sulfuric acid at room temperature to 150 °C.
C. for 1 to 10 hours. Some of the raw material compounds of the general formula [] are JP-A-52-
Although disclosed in No. 73875, the general formula The γ-keto acid represented by
General formula disclosed in No. 135785 It is prepared in good yield by subjecting the pyridazinone compound represented by the following to Wolff-Kitsschner reduction reaction. Reference example 1 4-(1,2,3,4-tetrahydro-2-oxoquinolin-6-yl)-4-oxobutanoic acid
Add 37 g of caustic potash, 59 g of caustic potash, and 60 ml of 80% hydrazine hydrate in 200 ml of triethylene glycol. While stirring, gradually raise the temperature,
Keep at 190-200℃ for 1 hour. After cooling, the reaction mixture is poured into ice water to which concentrated hydrochloric acid has been added.
When the crystals formed are collected, washed with water, and dried, 4-
30.7 g of (1,2,3,4-tetrahydro-2-oxoquinolin-6-yl)butanoic acid are obtained.
Melting point 185-188℃. Reference example 2 6-(1-methyl-2-oxo-1,2,3,
4-tetrahydroquinolin-6-yl)-4,5
Add 136 g of -dihydro-5-methyl-3(2H)-pyridazinone, 168 g of caustic potash, and 200 ml of 80% hydrazine hydrate to 600 ml of triethylene glycol, gradually heat and keep at 190-200°C for 2 hours.
After cooling, the reaction mixture was poured into ice water to which concentrated hydrochloric acid had been added in advance. The resulting crystals are collected, washed with water, and dried to give 4-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinoline-6-
115 g of yl)-3-methylbutanoic acid are obtained.
Melting point: 114-116°C The following raw material compound [] is obtained in the same manner. ◎ 4-(1-methyl-2-oxo-1,2,
3,4-tetrahydroquinolin-6-yl)butanoic acid Melting point 144-145℃ ◎ 4-(4-methyl-2-oxo-1,2,
3,4-tetrahydroquinolin-6-yl)butanoic acid Melting point 164-165℃ ◎ 4-(1-methyl-2-oxo-1,2,
3,4-tetrahydroquinolin-6-yl)-
2-Methylbutanoic acid Melting point 108-111℃ ◎ 4-(7-methyl-2-oxo-1,2,
3,4-tetrahydroquinolin-6-yl)butanoic acid Melting point 242-244℃ ◎ 4-(8-chloro-2-oxo-1,2,
3,4-tetrahydroquinolin-6-yl)-
3-Methylbutanoic acid Melting point: 137-139°C Next, the present invention will be specifically explained with reference to Examples. Example 1 4-(1-methyl-2-oxo-1,2,3,
4-tetrahydroquinolin-6-yl)butanoic acid
Add 23.5g to 120ml of concentrated sulfuric acid and heat to 100-110℃.
Keep time. Then, the reaction mixture is poured into ice, and the crystals formed are collected and washed with water. Recrystallization from ethanol gives colorless needle-shaped crystals of 1-methyl-2,9-
16.7 g of dioxo-1,2,3,4,6,7,8,9-octahydrobenzo[g]quinoline are obtained. Melting point 173-174℃ Example 2 4-(7-methyl-2-oxo-1,2,3,
4-tetrahydroquinolin-6-yl)butanoic acid
Add 30g to 150ml of concentrated sulfuric acid and keep at 100-110°C for 2 hours. Then, the reaction mixture is poured into ice, and the crystals formed are collected and washed with water. When recrystallized from ethyl alcohol, colorless needle-shaped crystals of 6-methyl-3,
10-dioxo-1,2,3,4,7,8,9,10
-22.3g of octahydrobenzo[f]quinoline is obtained. Melting point: 232-233°C Similarly, the following compound is obtained. Example 3 2,9-dioxo-1,2,3,4,6,7,
8,9-octahydrobenzo[g]quinoline Melting point 284-285°C Example 4 1-Butyl-2,9-dioxo-1,2,3,
4,6,7,8,9-octahydrobenzo [g]
Quinoline Melting point 96-98℃ Example 5 4-Methyl-2,9-dioxo-1,2,3,
4,6,7,8,9-octahydrobenzo [g]
Quinoline Melting point 230-231℃ Example 6 1,7-dimethyl-2,9-dioxo-1,
2,3,4,6,7,8,9-octahydrobenzo[g]quinoline Melting point 157-158°C Example 7 1,8-dimethyl-2,9-dioxo-1,
2,3,4,6,7,8,9-octahydrobenzo[g]quinoline Melting point 182-185°C Example 8 10-chloro-7-methyl-2,9-dioxo-
1,2,3,4,6,7,8,9-octahydrobenzo[g]quinoline Melting point 199-200°C Example 9 5-chloro-8-methyl-3,10-dioxo-
1,2,3,4,7,8,9,10-octahydrobenzo[f]quinoline Melting point 145-146°C.

Claims (1)

[Claims] 1 General formula [Formula] or [Formula] [In the formula, R ¹ is hydrogen or lower alkyl, R ² , R ³
are the same or different, hydrogen, lower alkyl,
R ⁴ represents hydrogen, lower alkyl, or halogen, R ⁵ represents hydrogen or lower alkyl, and R ⁶ represents hydrogen or lower alkyl. ] A benzoquinoline derivative represented by.