Egfr inhibitor, preparation method and use thereof

A compound selected from the group consisting of a compound of formula (IIIA1-7), a compound of formula (IIIA1-8), a compound of formula (IIIA1-9), a compound of formula (IVA1-4), a compound of formula (IVA-5), a compound of formula (IVA1-6), and a compound of formula (IVA1-7), or a stereoisomer or a pharmaceutically acceptable salt thereof:

• wherein
• R is selected from the group consisting of hydrogen and bis-C1-8 alkylaminomethyl;
• R1 is selected from the group consisting of:
• wherein the three R6 in
• are optionally the same or different substituents;
• R1 is selected from the group consisting of C1-8 alkyl and C3-8 cycloalkyl, wherein the C1-8 alkyl and C3-8 cycloalkyl are each optionally substituted by one or more groups selected from the group consisting of halogen, hydroxy, C1-8 alkyl, C1-8 alkoxy, haloC1-8 alkoxy, C3-8 cycloalkyl and C3-8 cycloalkoxy;
• R3 is selected from the group consisting of hydrogen, deuterium, halogen, cyano, nitro, C1-8 alkyl, C1-8 alkoxy, C3-8 cycloalkyl, trifluoromethyl, trifluoromethoxy, SO2R9, C(O)R10, C(O)OR10 and P(O)R11R12l;
• each R4 is independently selected from the group consisting of hydrogen, deuterium, halogen, hydroxy, sulfhydryl, cyano, nitro, azido, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3- to 8-membered heterocyclyl, 3- to 8-membered heterocyclyloxy, 3- to 8-membered heterocyclylthio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, 5- to 10-membered heteroaryl, 5- to 10-membered heteroaryloxy, 5- to 10-membered heteroarylthio, —C0-8—P(O)R11R12, —C0-8—S(O)rR9, —C0-8—O—R10, —C0-8—C(O)R10, —C0-8—C(O)OR10, —C-0-8—O—C(O)R10, —C0-8—NR7R8, —C0-8—C(O)NR7R8, —N(R7)—C(O)R10 and —N(R7)—C(O)OR10;
• wherein the C1-8 alkyl, C3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C5-10 aryl, 5- to 10-membered heteroaryl, 5- to 7-membered carbocycle, 5- to 7-membered heterocycle, C5-7 aryl and 5- to 7-membered heteroaryl are each optionally substituted by one or more groups selected from the group consisting of halogen, hydroxy, sulfhydryl, cyano, nitro, azido, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3- to 8-membered heterocyclyl, 3- to 8-membered heterocyclyloxy, 3- to 8-membered heterocyclylthio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, 5- to 10-membered heteroaryl, 5- to 10-membered heteroaryloxy, 5- to 10-membered heteroarylthio, —C0-8—S(O)rR9, —C0-8—O—R10, —C0-8—C(O)R10, —C0-8—C(O)OR10, —C0-8—O—C(O)R10, —C0-8—NR7R8, —C0-8—C(O)NR7R8, —N(R7)—C(O)R10 and —N(R7)—C(O)OR10;
• R6 is selected from the group consisting of hydrogen, deuterium, C1-8 alkyl, haloC1-8 alkyl and C(O)R10;
• R7 is selected from the group consisting of hydrogen, deuterium, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C5-10 aryl, 5- to 10-membered heteroaryl, —C0-8—S(O)rR9, —C0-8—O—R10, —C0-8—C(O)R10, —C0-8—C(O)OR10, —C0-8—O—C(O)R10, —C0-8—NR7R8 and —C0-8—C(O)NR7R8.
• wherein the C1-8 alkyl, C3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C5-10 aryl and 5- to 10-membered heteroaryl are each optionally substituted by one or more groups selected from the group consisting of halogen, hydroxy, sulfhydryl, cyano, nitro, azido, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3- to 8-membered heterocyclyl, 3- to 8-membered heterocyclyloxy, 3- to 8-membered heterocyclylthio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, 5- to 10-membered heteroaryl, 5- to 10-membered heteroaryloxy, 5- to 10-membered heteroarylthio, —C0-8—S(O)rR9, —C0-8—O—R10, —C0-8—C(O)R10, —C0-8—C(O)OR10, —C0-8—O—C(O)R10, —C0-8—NR7R8, —C0-8—C(O)NR7R8, —N(R7)—C(O)OR10 and —N(R)7—C(O)OR10;
• R8 is selected from the group consisting of hydrogen, deuterium, halogen, hydroxy, sulfhydryl, cyano, nitro, azido C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3- to 8-membered heterocyclyl, 3- to 8-membered heterocyclyloxy, 3- to 8-membered heterocyclylthio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, 5- to 10-membered heteroaryl, 5- to 10-membered heteroaryloxy, 5- to 10-membered heteroarylthio, —C0-8—S(O)rR9, —C0-8—O—R10, —C0-8—C(O)R10, —C0-8—C(O)OR10, —C0-8—O—C(O)R10, —C0-8—NR7R8, —C0-8—C(O)NR7R8, —N(R7)—C(O)R10 and —N(R7)—C(O)OR10,
• wherein the C1-8 alkyl, C3-8 cycloalkyl, 3- to 8-membered heterocyclyl, C5-10 aryl and 5- to 10-membered heteroaryl are each optionally substituted by one or more groups selected from the group consisting of halogen, hydroxy, sulfhydryl, cyano, nitro, azido, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3- to 8-membered heterocyclyl, 3- to 8-membered heterocyclyloxy, 3- to 8-membered heterocyclylthio, C5-10 aryl, C5-10 aryloxy, C5-10 arylthio, 5- to 10-membered heteroaryl, 5- to 10-membered heteroaryloxy, 5- to 10-membered heteroarylthio, —C0-8—S(O)rR9, —C0-8—O—R10, —C0-8—C(O)R10, —C0-8—C(O)OR10, —C0-8—O—C(O)R10, —C0-8—NR7R8, —C0-8—C(O)NR7R8, —N(R7)—C(O)R10 and —N(R7)—C(O)OR10;
• R9 is selected from the group consisting of hydrogen, deuterium, C1-8 alkyl, C3-8 cycloalkyl, haloC1-8 alkyl, bis-C1-8 alkylamino, phenyl and p-methylphenyl;
• R10, R11 and R12 are each independently selected from the group consisting of hydrogen, deuterium, C1-8 alkyl, C3-8 cycloalkyl, haloC1-8 alkyl and hydroxyC1-8 alkyl;
• m is 0, 1, 2, 3 or 4;
• r is 0, 1 or 2;
• q is 0,1,2,3 or 4;and
• “”
• means that substituent R can have a Z or E configuration.