5-iodopyrimidin-4-amine

A solution OF 4-AMINOPYRIMIDINE (O 970 g, 10. 3 mmol) in 20 mL of acetic acid was treated with iodine monochloride (1.67 g, 10.3 mmol, 1.01 equiv), which gave a copious precipitate of the N-IODO intermediate. The resulting mixture was refluxed for 3 hours under argon and cooled to about IO C with water bath. A precipitate formed that was collected and dried to provide the title compound as a yellowish solid (1.4 g, 62percent yield).A solution of 17 (0.2 g, 0.91 mmol) in anh. THF (20 mL) was cooled to 78 C in an acetone/CO2(s) bath under nitrogen.EtMgBr (0.33 mL, 1.0 mmol) was added dropwise and the reaction was stirred for two minutes, followed by the addition of TMSCl (0.14 mL, 1.09 mmol), after which the reaction was stirred for 5 min.Another addition of EtMgBr (0.33 mL, 1.0 mmol) was added dropwise, and the reaction was stirredfor 2 min; then, another addition of TMSCl (0.14 mL, 1.09 mmol) was added, and the reaction wasstirred for 5 min. A final addition of EtMgBr (0.33 mL, 1.0 mmol) was added, and the reaction stirredfor 10 min; then, ZnCl2 (1.81 mL, 1.81 mmol) was added dropwise. The solution was stirred at 78 Cfor 10 min, and then warmed to room temperature and stirred for 2 h. The organozinc mixture wasthen added dropwise to a solution of 9 (0.34 g, 1.0 mmol), Pd(PPh3)4 (0.11 g, 0.09 mmol), and CuI(0.01 g, 0.05 mmol) in anh. THF (10 mL). Then, the reaction stirred under nitrogen for 18 hours at roomtemperature. Upon completion, the reaction was quenched with saturated ethylenediaminetetraaceticacid (EDTA) (10 mL), after which it was concentrated in vacuo, extracted three times with CH2Cl2, washed with brine, and the organics were dried with MgSO4. After gravity filtration, the solvent wasremoved in vacuo to give a dark oil. Then, the crude mixture was purified twice via flash columnchromatography on silica (0-10% CH3OH (10% NH4OH) in DCM) to give the product as a pink oil(0.16 g, 48%);To a solution of 4-aminopyrimidine (0.80 g, 8.5 mmol) in glacial AcOH(20 mL) under nitrogen was added N-iodosuccinimide (2.30 g, 10.20 mmol) with stirring. The reactionrefluxed at 80 C for two hours. Upon completion, the reaction was cooled to room temperature, andthe solvent was removed in vacuo. The resulting yellow solid was resuspended in EtOAc, quenchedwith NaHCO3 (50 mL), washed with Na2S2O3 (50 mL), and the organic layer was dried with MgSO4and gravity filtered to give a yellow solid. Then, the crude product was purified by flash columnchromatography on silica (0-10% CH3OH in CH2Cl2) to give the pure product as a pale yellow solid(1.5 g, 80%); Rf = 0.48 (1:1 EtOAc: Hex); Spectral data is in agreement with literature values.14A solution OF 4-AMINOPYRIMIDINE (O 970 g, 10. 3 mmol) in 20 mL of acetic acid was treated with iodine monochloride (1.67 g, 10.3 mmol, 1.01 equiv), which gave a copious precipitate of the N-IODO intermediate. The resulting mixture was refluxed for 3 hours under argon and cooled to about IO C with water bath. A precipitate formed that was collected and dried to provide the title compound as a yellowish solid (1.4 g, 62% yield).Reference Example 45