2,4-Dichloro-5-(iodomethyl)pyrimidine

A mixture of 2, 4-Dichloro-5-chloromethyl-pyrimidine (10 g, 50.6 mmol), sodium iodide (7.69 g, 51.3 mmol) in acetone (60 ml) is stirred at room temperature for 20 min, then refluxed for 15 min. The reaction is allowed to cool to room temperature, then the solid is filtered and washed by acetone. The filtrate is concentrated to afford 2, 4-Dichloro-5-iodomethyl-pyrimidine as pale yellow solid (14.6 g, 100percent); 1H NMR 400 MHz (CDCl3) ' 8.54 (s, IH), 4.33 (s, 2H); MS m/z 288.9 (M + 1).A mixture of 2, 4-dichloro-5-(chloromethyl)pyrimidine (15.0 g, 76.0 mmoi), Nat (13.7 g, 91.4 mmoi) in acetone was stirred at 60 °C for 45 mm. The resulting precipitate (NaCl) was removed by filtration and washed with acetone. The combined filtrate was concentrated to give light yellow solid, which was purified by column chromatography on silica gel (eluting with DCM) to obtain 2, 4-dichloro-5- (iodomethyl)pyrimidine 2 as a light yellow solid (30.8 g, yield 96percent). LCMS (miz):289.3 [M + H].A mixture of 2, 4-dichloro-5-(chloromethyl)pyrimidine (15.0 g, 76.0 mmol), Nal (13.7 g, 91.4 mmol) in acetone was stirred at 60 °C for 45 min. The resulting precipitate (NaCl) was removed by filtration and washed with acetone. The combined filtrate was concentrated to give light yellow solid, which was purified by column chromatography on silica gel (eluting with DCM) to obtain 2, 4-dichloro-5-(iodomethyl)pyrimidine 2 as a light yellow solid (30.8 g, yield 96percent). LCMS (m z): 289.3 [M + H]To a solution of (2, 4-dichloro-5-iodomethyl)pyrimidine from Preparatory (6.07 g, 30.4 mmol, 1 eq.) in acetone (30 ml) was added sodium iodide (7.27 g, 30.4 mmol, 1 eq.) and the resulting mixture stirred at rt for 1 hour then heated to reflux and stirred for a further 30 minutes. The resulting mixture was cooled to rt and the precipitate filtered off. The filtrate was evaporated under reduced pressure and theresidue taken into diethyl ether (200 ml). The organics were successively washed with sodium metabisulfite (50 ml of a saturated solution), water (50 ml) and brine (50 ml), dried over MgSO4, filtered and concentrated under reduced pressure to afford the title compound (7.35 g, 84percent). ‘H NMR (400 MHz, DMSO) 8.62 (s, 1H), 4.41 (s, 2H); R= 0.68 (1:1 Petroleumether:EtOAc)To a solution of sodium iodide (23.4 g, 156.0 mmol) in dry acetone (150 mL), S9-2 (28.0 g, 141.8 mmol) was added at room temperature and stirred for 30 min. The resulting reaction mixture was warmed to 65° C. for 20 min. After completion, the reaction mixture was cooled to room temperature, filtered and washed with acetone (2×50 mL). The combined filtrate was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude material obtained was purified by flash column chromatography (silica gel 60-120, 10percent acetone in Pet. ether) to afford INT-53 (21 g, 48percent) as light yellow solid. Step 3: Intermediate 3 [00355j A 500-mL, three-necked flask equipped with a mechanical stirrer was charged with Intermediate 2 (32.0 g, 111 mmol), acetone (150 mL), Nal (26.5 g, 177 mmol). The mixture was allowed to stir at ambient temperature for 15 mm then was heated at reflux for 30 mm. The mixture was cooled to ambient temperature and filtered to remove the resultant solid. The filtrate was concentrated to afford 46.0 g of the title compound which was used in the next step without further purification.’H NMR (400 MHz, CDC13): ö 4.39 (s, 2H), 8.60 (s, 1H).To a stirred solution of 2, 4-dichloro-5-(chloromethyl)pyrimidine (1.50 g, 7.60 mmol) in acetone (10 mL), sodium iodide (1.20 g, 7.98 mmol) was added at room temperature. After 5 hours, the reaction mixture was filtered and the solid was washed with acetone. The filtrate and washed solution were combined and concentrated. The residue was purified on silica gel (eluting with 0-40percent EtOAc in hexanes) to give 1.5 g desired product. LCMS calculated for C[0229] To a stirred solution of 2, 4-dichloro-5-(chloromethyl)pyrimidine (1.50 g, 7.60 mmol) in acetone (10 mL), sodium iodide (1.20 g, 7.98 mmol) was added at room temperature. After stirring for 5 hours, the reaction mixture was filtered and the solid was washed with acetone. The filtrate and washed solution were combined and concentrated. The residue was purified on silica gel (eluting with 0-40percent EtOAc in hexanes) to give 1.5 g of the desired product. LCMS calculated for C5H4C121N2 [M+Hj mlz: 288.9; Found: 288.8.To a stirred solution of 2, 4-dichloro-5-(chloromethyl)pyrimidine (1.50 g, 7.60 mmol) in acetone (10 mL), sodium iodide (1.20 g, 7.98 mmol) was added at room temperature. After stirring for 5 hours, the reaction mixture was filtered and the solid was washed with acetone. The filtrate and washed solution were combined and concentrated. The residue was purified on silica gel (eluting with 0-40percent EtOAc in hexanes) to give 1.5 g of the desired product. LCMS calculated for C5H4CI2IN2 [M+H]

Molecular Weight:288.90
XLogP3:3.1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:287.87180
Monoisotopic Mass:287.87180
Topological Polar Surface Area:25.8
Heavy Atom Count:10
Complexity:114
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes