Triethylamine → HCID 71008715, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (R)-4-(1-(3-bromophenyl)-1H-pyrazol-4-yl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-1,3-oxazin-2-amine (227 mg, 612 μmol) (intermediate K7.1) in tetrahydrofuran (5 ml) was treated consecutively with ethynyltrimethylsilane (120 mg, 169 μl, 1.22 mmol), triphenylphosphine (4.81 mg, 18.3 μmol) and triethylamine (186 mg, 256 μl, 1.83 mmol). The mixture was degassed by bubbling argon through the solution, then copper(I) iodide (1.16 mg, 6.12 μmol) and bis(triphenylphosphine)palladium(II) chloride (21.5 mg, 30.6 μmol) were added. The reaction mixture was stirred at 70° C. in a sealed tube. In order to complete the reaction, ethynyltrimethylsilane (120 mg, 169 μl, 1.22 mmol) and bis(triphenylphosphine)palladium(II) chloride (21.5 mg, 30.6 μmol) were added again and stirring continued at 70° C. for 20 hours. Thereafter, the reaction mixture was evaporated and the residue purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 0:100 as the eluent. The (R)-5,5-difluoro-4-methyl-4-[1-(3-trimethylsilanylethynyl-phenyl)-1H-pyrazol-4-yl]-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (105 mg, 44% yield) was obtained as a brown, amorphous material. MS (ISP): m/z=389.3 [M+H]+.

Provenance & Evidence