Preparation method and application of isoxazinone compounds

A method for preparing a bisamide compound (V), comprising:

• reacting compound (II) with a carboxylic acid (III) in the presence of a dehydrating agent and a first base to produce the isoxazinone compound (I);
• and
• subjecting the isoxazinone compound (I) and a protonic acid salt of an amino compound (IV) to ring-opening reaction in the presence of a second base to produce the bisamide compound (V), as shown in the following reaction scheme:
• wherein:
• Q is N or C—Z;
• each R is independently alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cyano, carbonyl, alkoxycarbonyl, halogen, alkoxy, alkylthio, sulfonyl, sulftnyl, alkylamino or nitro;
• each Z is independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cyano, carbonyl, alkoxycarbonyl, halogen, alkoxy, alkylthio, sulfonyl, sulfinyl, alkylamino or nitro;
• n is 0, 1, 2 or 3;
• R′ is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;
• R1 and R2 are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl, but are not simultaneously hydrogen;
• and
• HY is hydrohalic acid, sulfuric acid, phosphoric acid or carboxylic acid.

A method for preparing an N-acyl benzoate compound (VI), comprising:

• reacting compound (II) with a carboxylic acid (III) in the presence of a dehydrating agent and a first base to produce the isoxazinone compound (I);
• and
• subjecting the isoxazinone compound (I) and R3OH (VII) to ring-opening reaction in the presence of a second base to produce the N-acyl benzoate compound (VI), as shown in the following reaction scheme:
• wherein:
• Q is N or C—Z;
• each R is independently alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cyano, carbonyl, alkoxycarbonyl, halogen, alkoxy, alkylthio, sulfonyl, sulftnyl, alkylamino or nitro;
• each Z is independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cyano, carbonyl, alkoxycarbonyl, halogen, alkoxy, alkylthio, sulfonyl, sulfinyl, alkylamino or nitro;
• n is 0, 1, 2 or 3;
• R′ is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl;
• and
• R3 is alkyl, substituted alkyl, alkenyl, alkynyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl.