Method for synthesis of 8-alkoxy-9h-isothiazolo[5,4-b]quinoline-3,4-diones

A compound of the formula

• wherein
• R1 is —SO2R4, —SOR4, —SH, or —SR4;
• where R4 is C1-C6alkyl, C2-C6alkenyl, (C3-C7cycloalkyl)C0-C4alkyl, (aryl)C0-C4alkyl, or (C2-C6heterocycloalkyl)C0-C2alkyl, each of which is substituted with 0 to 5 substituents independently chosen from halogen, hydroxy, amino, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, C1-C2haloalkyl, C1-C2haloalkoxy, mono- and di-C1-C4alkylamino, C2-C4alkanoyl, and C1-C4alkylthio;
• R2 is C1-C6alkyl, C2-C6alkenyl, (C3-C7cycloalkyl)C0-C4alkyl, (aryl)C0-C4alkyl, or (C2-C6heterocycloalkyl)C0-C2alkyl, each of which is substituted with 0 to 5 substituents independently chosen from halogen, hydroxy, amino, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, C1-C2haloalkyl, C1-C2haloalkoxy, mono- and di-C1-C4alkylamino, C2-C4alkanoyl, and C1-C4alkylthio;
• R5 is hydrogen, hydroxy, amino, C1-C2alkyl, C1-C2alkoxy, mono- or di-(C1-C4alkyl)amino, or mono- or di-C1-C4alkylhydrazinyl;
• R6 is hydrogen, halogen, or amino;
• R7 is a nitrogen-linked heterocycloalkyl group, which has 4 to 8 ring members, including 0, 1, or 2 additional ring heteroatoms independently chosen from N, O, and S;
• or
• R7 is a nitrogen-linked C1-C4alkylamino substituted with a 5 or 6-membered heteroaryl group having 1 or 2 heteroatoms independently chosen from N, O, and S, or substituted with a heterocycloalkyl group, which has 4 to 8 ring members, including 1 or 2 ring heteroatoms independently chosen from N, O, and S;
• or
• R7 is a nitrogen-linked heterocycloalkyl or heterocycloalkenyl group, each of which has 4 to 8 ring members, including 0, 1, or 2 additional ring heteroatoms independently chosen from N, O, and S, forming part of a bicyclic system with a 3- to 8-membered cycloalkyl or heterocycloalkyl ring in fused or spiro orientation;
• or
• R7 is a nitrogen-linked 6-membered heterocycloalkyl group, 0, 1, or 2 additional ring heteroatoms independently chosen from N, O, and S, and bridged with a methylene or ethylene bridge;
• or
• R7 is a group of the formula
• optionally attached to a C3-C7 spiro cycloalkyl or a spiro heterocycloalkyl;
• RA is hydrogen, or
• RA is C1-C8alkyl, C2-C6alkenyl, C2-C6alkynyl, C2-C6alkanoyl, (C3-C7cycloalkyl)C0-C4alkyl, (C4-C7cycloalkenyl)C0-C4alkyl, (aryl)C0-C4alkyl, (aryl)(C═O)—, or (C2-C6heterocycloalkyl)C0-C4alkyl, each of which is substituted with 0 to 5 substituents independently chosen from halogen, hydroxy, amino, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, C1-C2haloalkyl, C1-C2haloalkoxy, mono- and di-C1-C4alkylamino, C2-C4alkanoyl, and C1-C4alkylthio;
• RB is hydrogen or C1-C4alkyl;
• each of which R7 is substituted with 0 or 1 or more substituents independently chosen from (a) and 0, 1, or 2 substituents chosen from (b);
• wherein (a) is chosen from halogen, hydroxy, amino, nitro, C1-C4alkyl, C1-C4alkoxy, C1-C2haloalkyl, and C1-C2haloalkoxy, and (b) is oxo, cyano, hydroxyC1-C4alkyl, aminoC1-C4alkyl, C1-C6alkylthio, C2-C6alkanoyl, (mono- or di-C1-C4alkyl)aminoC0-C4alkyl, (C3-C7cycloalkyl)C0-C4alkyl,(C3-C7cycloalkyl)aminoC0-C4alkyl, (C3-C7cycloalkyl)(C1-C4alkyl)aminoC0-C4alkyl, (heterocycloalkyl)C0-C4alkyl, (5-membered heteroaryl)C0-C4alkyl, or (aryl)C0-C4alkyl, where each of (b) other than oxo and cyano is substituted with 0 to 2 substituents independently chosen from halogen, hydroxy, amino, cyano, nitro, oxo, —COOH, —CONH2, C1-C4alkyl, C1-C4alkoxy, mono- and di-(C1-C4alkyl)amino, C1-C2haloalkyl, and C1-C2haloalkoxy;
• R8 is C1-C6alkyl, C1-C2haloalkyl, or C3-C7cycloalkyl substituted with 0 or 1 or more halogen atoms;
• and
• R9 is C1-C4alkyl, cyclopropyl, or phenyl, each of which is substituted with 0 to 3 substituents independently chosen from halogen, hydroxy, amino, C1-C2alkyl, C1-C2alkoxy, mono- and di-(C1-C2)alkylamino, C1-C2haloalkyl, and C1-C2haloalkoxy.