6,7-dialkoxy quinazoline derivatives and methods of treating drug resistant and other tumors

A method of inhibiting a receptor tyrosine kinase in a subject in need thereof, the method comprising:

• administering to the subject an effective amount of a quinazoline derivative of formula (I)
• in which:
• R1 is:
• R2 is —CH3 or —CH2CH3;
• or
• a pharmaceutically acceptable salt thereof.

A method of inhibiting the growth of a tumor cell in a subject in need thereof, the method comprising:

• administering to the subject an effective amount of a quinazoline derivative of formula (I)
• in which:
• R1 is:
• R2 is —CH3 or —CH2CH3;
• or
• a pharmaceutically acceptable salt thereof.

A method of treating pancreatic cancer in a subject in need of treatment for pancreatic cancer, the method comprising:

• administering to the subject an effective amount of a quinazoline derivative of formula (I)
• in which:
• R1 is:
• R2 is —CH3 or —CH2CH3;
• or
• a pharmaceutically acceptable salt thereof.

A method of treating HER2 positive breast cancer in a subject in need of treatment for HER2 positive breast cancer, the method comprising:

• administering to the subject an effective amount of a quinazoline derivative of formula (I)
• in which:
• R1 is:
• R2 is —CH3 or —CH2CH3;
• or
• a pharmaceutically acceptable salt thereof.

A method of treating drug resistant non-small cell lung cancer in a subject in need of treatment for drug resistant non-small cell lung cancer, the method comprising:

• administering to the subject an effective amount of a quinazoline derivative of formula (I)
• in which:
• R1 is:
• R2 is —CH3 or —CH2CH3;
• or
• a pharmaceutically acceptable salt thereof.

A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a quinazoline derivative of formula (I)

• in which:
• R1 is:
• R2 is —CH3 or —CH2CH3;
• or
• a pharmaceutically acceptable salt thereof.

A process for preparing a quinazoline derivative of formula (I)

• in which:
• R1 is:
• R2 is —CH3 or —CH2CH3;
• or
• a pharmaceutically acceptable salt thereof;
• the process comprising:
• reacting a quinazoline of formula II:
• with phosphoryl chloride or oxalyl chloride to produce a chloro quinazoline of formula (III):
• condensing the 4-chloroquinazoline of formula III with 3-ethynyl aniline to produce the quinazoline derivative of formula (I).

A process for preparing a quinazoline derivative of formula (IA):

• the process comprising:
• reacting the quinazoline of formula (IIa):
• with phosphoryl chloride or oxalyl chloride to produce the corresponding 4-chloro quinazoline of formula (IIIa):
• condensing the 4-chloroquinazoline of formula III(a) with 3-ethynyl aniline to produce the quinazoline derivative of formula (IA).