N[C:2]1[N:11]=[CH:10][C:9]2[C:4](=[CH:5][C:6]([C:13]([O:15][CH3:16])=[O:14])=[CH:7][C:8]=2[F:12])[N:3]=1.[I:17]CI.N(OCCC(C)C)=O>C1COCC1.CCOC(C)=O.[Cu]I>[F:12][C:8]1[CH:7]=[C:6]([C:13]([O:15][CH3:16])=[O:14])[CH:5]=[C:4]2[C:9]=1[CH:10]=[N:11][C:2]([I:17])=[N:3]2A suspension of methyl 2-amino-5-fluoro-quinazoline-7-carboxylate (4.28 g, 19.3 mmol, 1.00 equiv), CuI (1.81 g, 9.5 mmol, 0.49 equiv) and diiodomethane (7.80 mL, 96.8 mmol, 5.0 equiv) in THF (80 ml) was treated with isoamyl nitrite (7.80 mL, 58.1 mmol, 3.00 equiv) at ambient temperature, and the mixture heated to 60 ° C. After 18 h the reaction was cooled. The mixture was diluted with EtOAc (100 mL), filtered through a Celite® pad, and the dark green filtrate concentrated in vacuo to an oily residue (23.0 g) which was absorbed onto SiO2 and purified by flash chromatography eluting with an EtOAc/heptane gradient (0 to 30% EtOAc) to afford 3.54 g (55%) of methyl 5-fluoro-2-iodoquinazoline-7-carboxylate as a cream-white solid: 1H NMR (400 MHz, CDCl3) δ 9.39 (s, 1H), 8.49 (s, 1H), 7.90 (d, J=9.5 Hz, 1H), 4.02 (s, 3H); LCMS: MH+333.0
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