Isopropyl iodide → HCID 68831377, compound

Participants

Reaction Steps

A solution of 8-bromo-7-(2-chloro-6-fluorobenzyl)-1-methyl-3,7-dihydro-1H-purine-2,6-dione (67 mg, 0.17 mmol) and K2CO3 (239 mg, 1.7 mmol) in 1.7 mL DMF was treated with isopropyl iodide (85 μL, 0.86 mmol). The reaction was stirred at room temperature for 15 hr. The reaction mixture was filtered through a silica plug and rinsed with EtOAc. The solvent was removed under reduced pressure and the crude product was purified by preparative thin layer chromatography (silica gel, 1 mm plate, EM Science 20×20 cm silica gel 60 F264) eluting with EtOAc:hexane (1:3) to give 46 mg (63% yield) of 8-bromo-7-(2-chloro-6-fluorobenzyl)-3-isopropyl-1-methyl-3,7-dihydro-1H-purine-2,6-dione. A solution of this intermediate (45 mg, 0.11 mmol) in 110 μL aqueous sodium carbonate (2 M), 270 μL toluene, and 45 μL ethanol was treated with 3-chlorophenylboronic acid (18 mg, 0.12 mmol), tetrakis(triphenylphosphine)palladium(0) (3.6 mg, 0.0032 mmol), and lithium chloride (catalytic). The reaction mixture was heated to 100° C. in a sealed vial and stirred overnight. The reaction mixture was cooled, filtered through a silica plug, and rinsed with 50% EtOAc:hexanes. The solvent was removed under reduced pressure and the crude product was purified by preparative thin layer chromatography (silica gel, 1 mm plate, EM Science 20×20 cm silica gel 60 h64) eluting with ether:hexane (1:1) to give 38 mg (77% yield) of the title compound as a white solid: 1H NMR (CDCl3, 400 MHz) 7.41-7.37 (m, 1H), 7.37-7.22 (m, 3H), 7.13-7.06 (m, 1H), 7.05-7.00 (m, 1H), 6.82-6.74 (m, 1H), 5.86 (s, 2H), 5.25-5.13 (m, 1H), 3.35 (s, 3H), 1.58 (d, 6H, J=7); MS (ESP+) m/e 461 (MH+); TLC (ether:hexanes/1:1) Rf=0.37.

Provenance & Evidence