Practical synthesis of benzoxazinones useful as HIV reverse transcriptase inhibitors

A process for the preparation of a compound of formula (IV):

• ##STR49## wherein:
• X is halogen,
• R.sup.2 is trihalomethyl or pentahaloethyl,
• R.sup.3 is cyclopropylethynyl;
• said process comprising:
• (a) contacting 5-halo-1-pentyne with about two equivalents of a suitable metallating agent to generate cyclopropylethynyl-lithium;
• and
• (b) contacting said cyclopropylethynyl lithium with a compound of formula (II):
• ##STR50## wherein R.sup.1 is an amine protecting group, which forms a carbamate with the amine, and
• (c) heating to a temperature sufficient to form a compound of formula (IV).

A process for the preparation of a compound of formula (IV):

• ##STR52## wherein:
• X is halogen,
• R.sup.2 is trihalomethyl or pentahaloethyl,
• R.sup.3 is cyclopropylethynyl;
• said process comprising:
• (a) contacting a compound of formula (I):
• ##STR53## wherein R.sup.1 is an amine protecting group, which forms a carbamate with the amine,
• with a suitable lithiating agent in a suitable solvent at a suitable temperature;
• (b) contacting the resultant product with a suitable disubstituted ketone of the formula R.sup.2 COR.sup.3, to form a compound of formula (III);
• and ##STR54## (c) heating the compound of formula (III) to a temperature suitable to form a compound of formula (IV).