Intermediates and synthesis for Endochin-like quinolone compounds

A method of preparation of a compound of the Formula (A):

• wherein:
• Ra, Rb, Rc, and Rd are each independently selected from the group of H, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C3 haloalkyl, aryl, nitro, cyano, amino, amido, acyl, carboxyl, substituted carboxyl, and —SO2Rh;
• Rh is selected from the group of H, C1-C6 alkyl, amino, or C1-C3 haloalkyl;
• Re is selected from the group of methyl, C1-C3 haloalkyl, and heteroaryl;
• Rf and Rg are independently selected from the group of H, C1-C6 alkyl, C1-C6 alkoxy, C1-C3 haloalkyl, C1-C3 haloalkoxy, methylsulfonyl, and halogen;
• n1 is integer selected from the group of 0, 1, 2, 3, 4, and 5;
• and
• n2 is integer selected from the group of 0, 1, 2, 3, 4, and 5;
• the method comprising the steps of:
• a) reacting a compound of Formula (1):
• wherein variables Ra, Rb, Rc, Rd, and Re are as defined for Formula (A), above, with iodine or bromine to produce a compound of Formula (2):
• wherein variables Ra, Rb, Rc, Rd, and Re are as defined for Formula (A), above, and Ri is selected from the group of Br and I;
• b) reacting the compound of Formula (2) with phosphoryl chloride and dichloromethane to produce a compound of Formula (3):
• wherein variables Ra, Rb, Rc, Rd, and Re are as defined for Formula (A), above, Ri is selected from Br and I;
• c) reacting the compound of Formula (3) with an optionally substituted 4,4,5,5-tetramethyl-2-(4-phenoxyphenyl)-1,3,2-dioxaborolane compound of the formula:
• wherein Rf, Rg, n1, and n2 are as defined for Formula (A), above;
• in the presence of a palladium catalyst to produce a compound of Formula (4):
• wherein variables Ra, Rb, Rc, Rd, Re, Rf, Rg, n1, and n2 are as defined for Formula (A), above;
• and
• d) reacting the compound of Formula (4) with cesium acetate and glacial acetic acid to produce a compound of Formula (A).