[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=2[F:15])[N:5]=[C:4]([C:16]([O:18][CH3:19])=[O:17])[CH:3]=1.[I:20](O)(=O)(=O)=O.II.S([O-])([O-])=O.[Na+].[Na+]>CO.ClCCl>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=2[F:15])[N:5]=[C:4]([C:16]([O:18][CH3:19])=[O:17])[C:3]=1[I:20]
Methyl 6-amino-2-(4-chloro-2-fluorophenyl)pyrimidine-4-carboxylate (6.17 g, 21.91 mmol, see US 20090088322 for preparation) was diluted with methanol (100 ml). Periodic acid (2.10 g, 9.21 mmol) and iodine (5.26 g, 20.72 mmol) were added and the reaction was heated at reflux overnight. The cooled reaction mixture was diluted with dichloromethane and poured into a 1N solution of sodium sulfite. The aqueous phase was extracted with dichloromethane. The combined organic phases were washed with 1N sodium sulfite, washed with saturated sodium chloride, dried over magnesium sulfate, filtered, and concentrated onto celite. Purification by flash chromatography (SiO2, 30% EtOAc:Hex) provided the title compound (1.46 g, 16% yield) as a white solid: 1H NMR (400 MHz, DMSO-d6) d 3.89 (s, 3H), 7.34-7.46 (m, 1H), 7.53 (dd, J=10.7, 2.0 Hz, 1H), 7.89 (t, J=8.4 Hz, 1H); 19F NMR (376 MHz, DMSO-d6) d −110.23; ESIMS m/z 408 ([M+H]+), 406 ([M−H]−).
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