5-AMINO-2-FLUOROBENZONITRILE

Step 31d. 3-Ethynyl-4-fluorobenzenamine (Compound 0605); Compound 0604 obtained above was treated with 100 mg potassium hydroxide in 20 mL of methanol at room temperature overnight. The solution was concentrated, dilute with water, brought to neutrality, and then extracted with ether. The combined organic phase was dried over magnesium sulfate, concentrated to yield the title compound 0605 as a brown oil (1.49 g, 85percent): LCMS 136 [M+1]Compound 0604 obtained above was treated with 100 mg potassium hydroxide in 20 mL of methanol at room temperature overnight. The solution was concentrated, dilute with water, brought to neutrality, and then extracted with ether. The combined organic phase was dried over magnesium sulfate, concentrated to yield the title compound 0605 as a brown oil (1.49 g, 85percent): LCMS 136 [M+l]Step 31d. 16 mg of potassium carbonate are added to a solution of 360 mg of 4-fluoro-3-[(trimethylsilyl)ethynyl]aniline in 5 ml of methanol. After stirring over night under argon and at a temperature in the region of 20° C., the medium is concentrated to dryness under reduced pressure, then taken up in 8 ml of water and neutralized with a few drops of hydrochloric acid (1 N), and then extracted three times with diethyl ether. The combined organic phases are dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. 225 mg of 3-ethynyl-4-fluoroaniline are obtained in the form of a brown oilStep 31d. 3-Ethynyl-4-fluorobenzenamine (Compound 0605); Compound 0604 obtained above was treated with 100 mg potassium hydroxide in 20 mL of methanol at room temperature overnight. The solution was concentrated, dilute with water, brought to neutrality, and then extracted with ether. The combined organic phase was dried over magnesium sulfate, concentrated to yield the title compound 0605 as a brown oil (1.49 g, 85percent): LCMS 136 [M+1]Compound 0604 obtained above was treated with 100 mg potassium hydroxide in 20 mL of methanol at room temperature overnight. The solution was concentrated, dilute with water, brought to neutrality, and then extracted with ether. The combined organic phase was dried over magnesium sulfate, concentrated to yield the title compound 0605 as a brown oil (1.49 g, 85percent): LCMS 136 [M+l]Step 31d. 16 mg of potassium carbonate are added to a solution of 360 mg of 4-fluoro-3-[(trimethylsilyl)ethynyl]aniline in 5 ml of methanol. After stirring over night under argon and at a temperature in the region of 20° C., the medium is concentrated to dryness under reduced pressure, then taken up in 8 ml of water and neutralized with a few drops of hydrochloric acid (1 N), and then extracted three times with diethyl ether. The combined organic phases are dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. 225 mg of 3-ethynyl-4-fluoroaniline are obtained in the form of a brown oil4-Chloro-6, 7-bis-(2-methoxy-ethoxy)-quinazoline (140 mg, 0.446 mmol) and Step 4. 4-(3-Ethynyl-4-fluorophenylamino)quinazoline-6, 7-diol (26). To a solution of 13 (0.800 g, 2.10 mmol) in CHCl3 (10 mL) was added 3-ethynyl-4- fluoroaniline 24d (0.311 g, 2.31 mmol, prepared as described in J Org Chem, 1981, 2280-2296) and the solution was stirred at reflux overnight. The solids obtained were filtered and dried to give the diacetyl product 25 (0.700 g, 70%). The product 25 was stirred with ammonia in MeOH (2 mL) for 1 hour at room temperature. The mixture was concentrated in vacuo and the residue was washed with water (5 mL) and filtered to give the product 26 (0.300 g, 55%).A suspension of 4-chloro-7-methoxyquinazolin-6-yl acetate (4.31 g), Step 31e. 4-(3-Ethynyl-4-fluorophenylamino)-7-methoxyquinazolin-6-yl acetate (Compound 0606) A mixture of 4-chloro-7-methoxyquinazolin-6-yl acetate (compound 0105) (252 mg, 1.0 mmol) and Step 31e. 4-(3-Ethynyl-4-fluorophenylamino)-7-methoxyquinazolin-6-yl acetate (Compound 0606); A mixture of 4-chloro-7-methoxyquinazolin-6-yl acetate (compound 0105) (252 mg, 1.0 mmol) and A suspension of 4-chloro-7-methoxyquinazolin-6-yl acetate (4.31 g), Step 31d. 3-Ethynyl-4-fluorobenzenamine (Compound 0605); Compound 0604 obtained above was treated with 100 mg potassium hydroxide in 20 mL of methanol at room temperature overnight. The solution was concentrated, dilute with water, brought to neutrality, and then extracted with ether. The combined organic phase was dried over magnesium sulfate, concentrated to yield the title compound 0605 as a brown oil (1.49 g, 85%): LCMS 136 [M+1]+. The product was used in the next step without further purification.Compound 0604 obtained above was treated with 100 mg potassium hydroxide in 20 mL of methanol at room temperature overnight. The solution was concentrated, dilute with water, brought to neutrality, and then extracted with ether. The combined organic phase was dried over magnesium sulfate, concentrated to yield the title compound 0605 as a brown oil (1.49 g, 85%): LCMS 136 [M+l]+. The product was used in the next step without further purification.Step 31d. 3-Ethynyl-4-fluorobenzenamine (Compound 0605) Compound 0604 obtained above was treated with 100 mg potassium hydroxide in 20 mL of methanol at room temperature overnight. The solution was concentrated, dilute with water, brought to neutrality, and then extracted with ether. The combined organic phase was dried over magnesium sulfate, concentrated to yield the title compound 0605 as a brown oil (1.49 g, 85%): LCMS 136 [M+1]+. The product was used in the next step without further purification.16 mg of potassium carbonate are added to a solution of 360 mg of 4-fluoro-3-[(trimethylsilyl)ethynyl]aniline in 5 ml of methanol. After stirring over night under argon and at a temperature in the region of 20 C., the medium is concentrated to dryness under reduced pressure, then taken up in 8 ml of water and neutralized with a few drops of hydrochloric acid (1 N), and then extracted three times with diethyl ether. The combined organic phases are dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure. 225 mg of

Molecular Weight:135.14
XLogP3:1.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:135.048427358
Monoisotopic Mass:135.048427358
Topological Polar Surface Area:26
Heavy Atom Count:10
Complexity:158
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes