6-(Polyhaloisopropyl)quinazoline-2,4-Diones

The following examples describe in detail compounds and compositions illustrative of the present invention. It will be apparent to those skilled in the art that many modifications, both of materials and methods, may be practiced without departing from the purpose and intent of this disclosure.

Combine 16.5 g (0.1 mole) of ethyl anthranilate with 38.6 g (0.20 mole) of hexafluoroacetone sesquihydrate and reflux 24 hours. Add 19.3 g (0.1 mole) of hexafluoroacetone sesquihydrate to the reaction mixture and reflux for another 24 hours. Distill off the excess hexafluoroacetone hydrate in vacuo. Wash the residual solid with hexane and obtain 25 g of pink solid. Recrystallize from ethanol and H.sub.2 O to obtain 20 g of ethyl-5-(hexafluoro-2-hydroxy-2-propyl)anthranilate as a pink solid; m.p. 115.degree.-117.degree. C.

Combine 4.3 g (13 mmole) of ethyl 5-(hexafluoro-2-hydroxy-2-propyl)anthranilate from the preceeding example, and 1.8 g (26 mmole) of ethyl isocyanate with 20 ml of Et.sub.2 O. Reflux for 5 days. Each day add another 1.8 g portion of ethyl isocyanate. Concentrate the reaction mixture to obtain 5.5 g of a white solid. Recrystallize from Et.sub.2 O-hexane to obtain 4.5 g of N-ethyl-N'-[4-(hexafluoro-2-hydroxy-2-propyl)-2-(ethoxycarbonyl)phenyl]ure a as a white solid; m.p. 144.degree.-146.degree. C.

Combine 4.02 g (10 mmole) of N-ethyl-N'-[4-(hexafluoro-2-hydroxy-2-propyl)-2-(ethoxycarbonyl)phenyl]ure a with 21 ml (20 mmole) 1N NaOH and stir for 1 minute. Acidify the reaction with 1N HCl and extract with 100 ml of Et.sub.2 O. Dry and concentrate the extract to obtain 3.5 g of white solid. Recrystallize from Et.sub.2 O-hexane to obtain 2.5 g of white solid 3-ethyl-6-(hexafluoro-2-hydroxy-2-propyl)quinazoline-2,4-dione; m.p. 268.degree.-270.degree. C.

Repetition of the procedures detailed in the above examples using the appropriate starting materials affords the following compounds of this invention:

6-(1,3-dichloro-2-hydroxytetrafluoro-2-propyl)-3-ethylquinazoline-2,4-dione ;

3-ethyl-6-(hexafluoro-2-hydroxy-2-propyl)-1-methylquinazoline-2,4-dione;

6-(chloro-2-hydroxypentafluoro-2-propyl)-3-ethyl-1-methylquinazoline-2,4-di one;

3-ethyl-6-(hexafluoro-2-hydroxy-2-propyl)quinazoline-2,4-dione;

3-bromoethyl-6-(hexafluoro-2-hydroxy-2-propyl)quinazoline-2,4-dione;

7-methyl-6-(hexafluoro-2-hydroxy-2-propyl)-3-ethylquinazoline-2,4-dione;

8-propyl-6-(hexafluoro-2-hydroxy-2-propyl)-3-ethylquinazoline-2,4-dione;

7-chloro-6-(hexafluoro-2-hydroxy-2-propyl)-3-ethylquinazoline-2,4-dione;

8-methoxy-6-(hexafluoro-2-hydroxy-2-propyl)-3-ethylquinazoline-2,4-dione.

Mix together the stated active ingredient, lactose, microcrystalline cellulose, sodium lauryl sulfate, and corn starch. Pass through a No. 40 screen. Add magnesium stearate, mix and compress into desired shape on a tablet machine.

Mix together the stated active ingredient, lactose, dicalcium phosphate and sodium lauryl sulfate. Screen the above mixture through a No. 60 screen and granulate with an aqueous solution containing polyvinylpyrrolidone. Add additional water, if necessary, to bring powders to a pasty mass. Add corn starch and continue mixing until uniform granules are formed. Pass through a No. 10 screen, tray and dry in an oven at 40.degree. C for 12 to 14 hours. Reduce the dried granulation through a No. 16 screen. Add magnesium stearate, mix and compress into desired shape on a tablet machine.

Mix together the stated active ingredient, lactose, microcrystalline cellulose, sodium lauryl sulfate and corn starch. Pass through a No. 80 screen. Add magnesium stearate, mix and encapsulate into the proper size two-piece gelatin capsule.