4-(4-Bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline Chemical Properties

Melting point:

268-270 °C

Boiling point:

471.0±45.0 °C(Predicted)

Density 

1.663

storage temp. 

Keep in dark place,Inert atmosphere,Room temperature

solubility 

DMSO (Slightly), Methanol (Slightly, Heated)

form 

Solid

pka

5.51±0.40(Predicted)

color 

White to Off-White

InChI

InChI=1S/C15H11BrFN3O2/c1-22-14-5-9-12(6-13(14)21)18-7-19-15(9)20-11-3-2-8(16)4-10(11)17/h2-7,21H,1H3,(H,18,19,20)

InChIKey

XIHOMGRMQWNHHB-UHFFFAOYSA-N

SMILES

N1=C2C(C=C(OC)C(O)=C2)=C(NC2=CC=C(Br)C=C2F)N=C1

4-(4-Bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline Usage And Synthesis

Uses

4-(4-Bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazolin is used in the synthesis of [18F]-(R)-FEPAQ, a potential PET imaging agent for VEGFR2. This would be helpful in the imaging of VEGFR in cance r patients.

Synthesis

General procedure for the synthesis of 4-(4-bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline from 7-(benzyloxy)-N-(4-bromo-2-fluorophenyl)-6-methoxyquinazolin-4-amine: the intermediate 7-(benzyloxy)-N-(4-bromo-2-fluorophenyl)-6-methoxyquinazolin-4-amine (1.30 g, 2.86 mmol) was dissolved in trifluoroacetic acid (15 mL) and the solution was heated to reflux for 1.5 hours. Upon completion of the reaction, the solution was cooled to room temperature and concentrated under reduced pressure. Methanol (20 mL) was added to the residual brown solid and the pH was adjusted with concentrated ammonium hydroxide solution to 11. The mixture was concentrated under reduced pressure and dried under high vacuum, and then purified by fast column chromatography on a silica gel column (20 g) with the eluent being a dichloromethane solution of 5-20% methanol. This step afforded the target product 4-(4-bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (1.03 g, 99% yield) as a light yellow solid.1H NMR (300 MHz, DMSO-d6): δ 10.5 (br s, 1H), 9.53 (br s, 1H), 8.34 (s, 1H), 7.81 (s, 1H). 7.63 (d, 1H, J = 9.6 Hz), 7.54 (dd, 1H, J = 8.4, 7.8 Hz), 7.44 (d, 1H, J = 8.4 Hz), 7.12 (s, 1H), 3.95 (s, 3H).13C NMR (75 MHz, DMSO-d6): δ 156.77, 156.49, 152.92, 152.62, 148.62, 146.74, 129.40, 127.39, 126.46 (d, J = 12 Hz), 119.23 (d, J = 23.2 Hz), 117.4 (d, J = 8.3 Hz), 109.96, 108.08, 102.23, 56.09.

References

[1] Patent: WO2005/97134, 2005, A2. Location in patent: Page/Page column 17-18; figure 2
[2] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 11, p. 3222 - 3226
[3] Patent: US2010/75916, 2010, A1. Location in patent: Page/Page column 16
[4] Patent: WO2005/13998, 2005, A1. Location in patent: Page/Page column 75-76
[5] Patent: WO2012/30160, 2012, A2. Location in patent: Page/Page column 52