[Synthesis]
General procedure for the synthesis of 4-chlorofuro[2,3-d]pyrimidines from furo[2,3-d]pyrimidin-4-amines: via a modified Sandmeyer reaction, a mixture of 4-amino furo[2,3-d]pyrimidines (303 mg, 2.24 mmol), tert-butyl nitrite (5.3 mL, 44.6 mmol) and TMSCl (1.4 mL. 11.07 mmol) in acetonitrile (5.0 mL) was stirred at 50 °C for 1.5 hours. After completion of the reaction, the reaction was quenched with 1N NaOH solution and the aqueous phase was thoroughly extracted with EtOAc. The organic extracts were combined, washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel chromatography using 10% EtOAc/hexane as eluent to afford the target product 4-chlorofuro[2,3-d]pyrimidine (139 mg, 40% yield). The structure of the product was confirmed by 1H NMR (500 MHz, CDCl3, δ: 8.68 (s, 1H), 7.72 (d, J = 2.5 Hz, 1H), 6.84 (d, J = 2.5 Hz, 1H)) and 13C NMR (125 MHz, CDCl3, δ: 167.1, 154.0, 153.5, 146.0, 177.9, 177.7, 177.9, 177.9, 177.9). 104.7) was confirmed. Mass spectrometry analysis showed m/z (relative intensities) of 154 (M+, 100), 119 (37), 98 (21). References: (a) Bracher, F.; Daab, J. Eur. J. Org. Chem. 2002, 2288. (b) Doyle, M. P.; Siegfried, B.; Dellaria, J. F. J. Org. Chem. 1977, 42, 2426. (26) Nakano, M.. Maeda, Y. WO 2005061516 A1 20050707 CAN 143:115566. |