Methods for preparing tyrosine receptor kinase inhibitors

A method for making a compound having the structure represented by formula (XV):

• or a pharmaceutically acceptable salt thereof, the method comprising coupling a compound of formula (XVI):
• and a compound of formula (XVII):
• whereby
• replaces X1;
• wherein X1 is a leaving group;
• wherein R10 is selected from hydrogen, halogen, —CN, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, —OR20, —C(O) R20, —S(O) R20, —S(O)2R20, —(C1-C6 alkyl)OR20, —(C1-C6 alkyl)SR20, —(C1-C6 alkyl)C(O)R20, —(C1-C6 alkyl)S(O)R20, —(C1-C6 alkyl)S(O)2R20, —NR21C(O)R20, —NR21S(O)2R20, —NR22aR22b, —P(O)R22aR22b, —(C1-C6 alkyl)NR22aR22b, —(C1-C6 alkyl) P(O)R22aR22b, and Cy1;
• wherein each of R20, R21, R22a, and R22b, when present, is independently selected from hydrogen, C1-C4 alkyl, and C1-C4 haloalkyl;
• wherein Cy1, when present, is selected from a C3-C8 cycloalkyl, a 3- to 8-membered heterocycloalkyl, a C6-C10 aryl, and a 5- to 10-membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, —CN, —NH2, —OH, —NO2, C1-C4 alkyl, C2-C4 alkenyl, C1-C4 haloalkyl, C1-C4 cyanoalkyl, C1-C4 hydroxyalkyl, C1-C4 haloalkoxy, C1-C4 alkoxy, C1-C4 alkylamino, (C1-C4) (C1-C4) dialkylamino, and C1-C4 aminoalkyl;
• and
• wherein Ar2 is a C6-C10 aryl or a 5- to 6-membered heteroaryl, and is substituted with 0, 1, 2, or 3 groups independently selected from halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, and C1-C6 haloalkoxy.