JPS5942677B2 - 100% free of charge - Google Patents

Description

Detailed Description of the Invention The present invention is based on the general formula □H゛)n(I) (wherein X represents a hydrogen atom, a halogen atom, a lower alkyl group or a nitro group, and n is an integer of 3, 4 or 5) This invention relates to a method for producing a condensed quinazolinone derivative and its salt.

Conventionally, methods for producing fused quinazolinone derivatives have been described in Justus Liebitz Annaren der Chemie 6.
Volume 23, page 166, 1959 (Ju-stus Liebi
gsAnnalemderChmie) and Gazetteer Chimica Italiana, Vol. 99, p. 59, 1969 (
Ga22ettaChimicaItalia1na)
and Zhurnal Obshche Himii, vol. 38, p. 2030, 1968.
iKhimii) and Chemische Berichte, vol. 68, p. 2221, 1953.
hte) and others.

However, all of these methods have drawbacks such as long reaction steps, high-temperature heat treatment, and low yields, and are unsuitable for industrial use. The present inventors conducted various studies in view of these drawbacks, and as a result, they found an industrially excellent method that has a low reaction temperature, high yield, and simple reaction treatment, and completed the present invention.

That is, in the present invention, a compound represented by the general formula ° (■) (wherein X represents a hydrogen atom, a halogen atom, a lower alkyl group, or a nitro group) is reacted with thionyl halide, and then a compound represented by the general formula (wherein n is A method for producing a condensed quinazolinone derivative represented by the general formula (wherein X and n have the same meanings as above), characterized by reacting a compound represented by the formula (meaning an integer of 3, 4 or 5). .

In carrying out the present invention, thionyl halide is dissolved in a nonpolar solvent such as benzene, toluene, xylene, dichloromethane, chloroform, carbon tetrachloride, etc., and the compound is added to the solution.

The resulting solution is then refluxed for 1 to 5 hours, and then the remaining thionyl halide and solvent are distilled off under reduced pressure. The resulting residue is dissolved in a non-polar solvent, and then added to a solution of the compound in a non-polar solvent at 2-20°C, preferably 5-10°C.
The dropwise addition takes 0 to 90 minutes, preferably 10 to 40 minutes. The resulting solution is then stirred at room temperature to 50°C for 1 to 6 hours to collect the precipitated crude crystals, dried, and then mixed with an organic solvent such as methanol, ethanol, acetone, N,N-dimethylformamide, dimethyl sulfoxide. The target compound 1 is obtained by recrystallization from a mixed solvent or a mixed solvent thereof. In addition, Compound 1 can be treated with a conventional method as necessary to form a hydrochloride.
They can be inorganic acid salts such as hydrobromide, sulfate, phosphate, and organic acid salts such as acetate, succinate, maleate, citrate. The compounds obtained in this way include new compounds not described in the literature, and have antidepressant effects,
It has pharmacological effects such as antihypertensive and anti-inflammatory effects, and is useful as a medicine.

Next, an example will be given and explained.

Example 1 Preparation of 123-trihydroJmethyl-9H-la-9pyrrolo[2,1-b]-quinazoline Onthionyltalolide 79 was dissolved in 15 ml of benzene,
2-Amino-5-methylbenzoic acid 39 is gradually added to the solution under water cooling.

The solution was then refluxed for 2 hours, and then benzene and remaining thionyl chloride were distilled off under reduced pressure. The residue was dissolved in 15 ml of tetrahydrofuran, and 1.5 ml of α-pyrrolidone was added.
79 in 15 ml of tetrahydrofuran was added dropwise with stirring at 5 to 1°C over 20 minutes. The resulting solution was then stirred at room temperature for 5 hours, and the precipitated crude product was collected and dried to obtain 3.8 g of crude crystals. The crude crystals are recrystallized from dilute methanol to obtain colorless acicular crystals of 1,2,3-trihydro-Me[methyl-9H-pyrrolo[2,1-b]-quinazolin-9-one. The 1,2,3-trihydroJ-9-one obtained above is treated in a conventional manner to obtain the hydrochloride.

Melting point 209-211 CExample 2 6789-Tetrahytrose 2-nitrotura 11H-pyrido[2,1-b]-quinazolin 11-one is dissolved in the solution and 2-amino-5-nitrobenzoic acid is added to the solution. 3.69 is gradually added under water cooling.

The solution was then refluxed for 3 hours, and then chloroform and remaining thionyl chloride were distilled off under reduced pressure. Dissolve the residue in 10 WLI of chloroform and dissolve δ-valerolactam 2
9 in 20 ml of chloroform while stirring.
Add dropwise at 10°C over 30 minutes. Next, the mixture was stirred at room temperature for 4 hours, the precipitated crude product was filtered out and dried, and the crude crystals were collected for 4 hours.
．． Get 19. The crude crystals were recrystallized from dilute dimethyl sulfoxide to give light brown needle-like crystals of 6,7,8,9-tetrahytone-2-nitro-11H-pyrido[2,1-b]-
Quinazolin-11-one is obtained. Example 3 Preparation of 678910-pentahytrose-2-nitro-12H-azepino[2,1-b)-quinazolin-112-one When treated in the same manner as in Example 2, 6,7,8,9,10-pentahythro-2-nitro-12H -Azepino [2,1-b
]-quinazolin 12-one is obtained.

Examples 4 to 11 When treated in the same manner as in Example 1, the compounds shown in the following table are obtained.

Claims (1)

[Claims] 1. A compound represented by the general formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (wherein X represents a hydrogen atom, a halogen atom, a lower alkyl group, or a nitro group) is reacted with thionyl halide, Next, there are general formulas ▲ mathematical formulas, chemical formulas, tables, etc. ▼ general formulas characterized by reacting compounds represented by (n in the formula means an integer of 3, 4, or 5) ▲ mathematical formulas, chemical formulas, tables, etc. There is a method for producing a condensed quinazolinone derivative represented by ▼ (wherein X and n have the same meanings as above).