Process for preparing 2,4-dihaloquinazolines
AssigneeBristol-Myers Company
InventorsRonnie Ray Crenshaw, George Michael Luke, Richard Anthony Partyka
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Abstract
A one-step process for the preparation of 2,4-dihaloquinazolines is disclosed beginning with methoxycarbonyl- or phenoxycarbonyl-derivatives of substituted phenylureas which are cyclized and concomitantly halogenated with a cyclizing-halogenating reagent such as N,N-dimethylaniline in phosphorus oxychloride. The 2,4-dihaloquinazolines of the instant process are particularly valuable as intermediates in the preparation of 4-amino-2-(4-substituted-piperazin-1-yl) quinazolines useful in the treatment of cardiovascular disorders such as hypertension.
Claims10
A process for preparing a compound of formula I ##STR12## wherein X is halogen selected from the group consisting of chlorine and bromine;
- and
- R.sub.1, r.sub.2 and R.sub.3 are independently selected from the group consisting of hydrogen, lower alkyl of 1 to 4 carbon atoms inclusive and lower alkoxy of 1 to 4 carbon atoms inclusive;
- which comprises treating a compound of formula II ##STR13## wherein R.sub.1, R.sub.2 and R.sub.3 are as above and A is methyl or phenyl with a reagent selected from the group consisting of (a) hydrogen chloride in phosphorus oxychloride, (b) hydrogen bromide in phosphorus oxybromide, (c) phosphorus oxychloride and N,N-dimethylaniline, and (d) phosphorus oxybromide and N,N-dimethylaniline and thereafter completing the cyclization and halogenation reaction by heating at reflux temperature to produce the quinazoline compound of formula I.
A process for the preparation of a quinazoline of formula III ##STR14## which comprises treating a phenoxycarbonylurea having formula IV ##STR15## with N,N-dimethylaniline in a solvent amount of phosphorus oxychloride and thereafter refluxing the reaction mixture to complete the cyclization and chlorination reaction.
A process for the preparation of a quinazoline of formula V ##STR16## which comprises treating a phenoxycarbonylurea having formula VI ##STR17## with N,N-dimethylaniline in a solvent amount of phosphorus oxychloride and thereafter refluxing the reaction mixture to complete the cyclization and chlorination reaction.
Dependencies are inferred from the claim text.