Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
  • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
  • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

• the invention concerns 2-(4-substitutedpiperidino)- 4-amino-6,7-dimethoxyquinazolines. These new compounds have valuable pharmacological properties.
• Patents FR 2 350 101 and PR 2 389621 refer to 2-(4-phenylpiperidino)-4-amino-6,7-dimethoxyquinazoline and corresponding compounds, in which the phenyl group is subs tituted with a fluoro or methoxy group.
• Published patent application PI 80 0481 refers to 2-(4-alkylcarbonylpiperidino)- and 2-(4-cycloalkylcarbonyl- piperidino)-4-amino-6,7-dimethoxyquinazoline.
• This invention deals with compounds of the formula
• R is a cycloalkyl containing 3 to 7 carbon atoms, an alkenyl containing 2 to 6 carbon atoms, or a benzyl group.
• This invention also deals with the methods for the preparation of the compounds with formula I, in which a) a compound with the formula
• the invention also deals with the compounds of formula II, which are valuable intermediates for the prepara tion of the formula I compounds.
• the formula I compounds can be used as pharmaceutical agents for the treatment of hypertension.
• Pormula VI compounds can be pre pared from the corresponding ketones by reduction.
• 4-(1-nydroxyethyl.)piperidi ⁇ e is l ⁇ fow ⁇ from J. Org. Chem.
• the method;e -reduction is carried out with hydrogen under about 1 to 7 atm pressure and at about 20 to 100°C using common hydrogenation catalysts such as palladium, platinum or nickel.
• common hydrogenation catalysts such as palladium, platinum or nickel.
• Other reducing agents can also be used, e.g. sodium borohydride or aluminium isopropoxide.
• Example 1 1.3 g of NaBH 4 in 15 ml of water is added at 0 °C toa-solution of 4.7 g (0.026 mol) of 4-cyclopentylcarbonyl- piperidine in 50 ml of methanol. This is stirred for 1 h at 0 °C and for 2 h at 20 °C. The methanol is evaporated off, water is added and the solution is extracted with chloroform and the extract evaporated to dryness. 3.4 g of 4-(1-hydroxy-1-cyclopentylmethyl)piperidine (VI) is obtained; mp. 123 - 5 °C, yield 72 %.
• Method e 1.2 g of NaBH.in 10 ml of water is added in an ice bath to a solution of 4.35 g (0.01 mol) of 2-(4-cyclohexylcarbonylpiperidino)-4-amino-6,7-dimethoxy- quinazoline hydrochloride and 20 ml of 0.5 N NaOH solution in 80 ml of methanol. The solution is stirred for 1 h at 0 °C and for 18 h at 20 °C. Some of the methanol is removed under reduced pressure, the precipitate formed is filtered off, washed with water and dried. The product is dissolved in acetone and precipitated with gaseous HCl.
• Method c A solution of 2.4 g (0.01 mol) of 2-chloro- 4-amlno-6,7-dimethoxyquinazoline and 2.0 g (0.01 mol) of 4-(1-hydroxy-1-cyclohexylmethyl)piperidine in 30 ml of iso amyl alcohol is refluxed for 18 h and cooled. The precipitated product is filtered, washed with ether and dried. De sired product is obtained.
• Method d A solution of 2.5 g (0.01 mol) of S-methyl- N-cyano-N'-(3-,4 dimeth ⁇ xyphenyl)isothioufea and 3.0 g (0.01 mol) or 4-(1-hydroxy-1-cyclohexylmethyl)piperidine in 35 ml of diglycoldimethylether Is refluxed for 5 h and cooled.Water is added to the mixture, followed by extraction with chloroform. The solvent is evaporated off from the extract, and the residue is dissolved in acetone, into which HCl gas is led. Desired product is obtained.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Plural Heterocyclic Compounds (AREA)
• Hydrogenated Pyridines (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (2)

Publications (1)

Family

ID=8514689

Family Applications (1)

Country Status (11)

Family Cites Families (6)

• 1982
  • 1982-08-28 ES ES515338A patent/ES515338A0/es active Granted
  • 1982-09-03 WO PCT/FI1982/000034 patent/WO1983000866A1/en not_active Application Discontinuation
  • 1982-09-03 EP EP82902731A patent/EP0087456A1/en not_active Withdrawn
  • 1982-09-03 JP JP57502713A patent/JPS58501513A/ja active Pending
  • 1982-09-03 AU AU89066/82A patent/AU8906682A/en not_active Abandoned
  • 1982-09-08 ZA ZA826596A patent/ZA826596B/xx unknown
  • 1982-09-08 PT PT75525A patent/PT75525B/pt unknown
  • 1982-09-08 IT IT23168/82A patent/IT1156319B/it active
• 1983
  • 1983-04-25 DK DK1810/83A patent/DK181083D0/da not_active Application Discontinuation
  • 1983-05-06 NO NO831622A patent/NO831622L/no unknown
  • 1983-05-09 FI FI831585A patent/FI831585A0/fi not_active Application Discontinuation

Non-Patent Citations (1)

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