(2R)-1-iodopropan-2-ol

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 4-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-2-(5-(4,5-dihydro-4-methyl-5-oxotetrazol-1-yl)-2-fluoro-4-hydroxyl-phenylamino)pyrimidine-5-carbonitrile (467 mg, 1.0 eq.) was added to N,N-dimethylacetamide (4.7 ml, 0.2M), followed by Cs2CO3 (922 mg, 3.0 eq.) and 3-iodo-2-(R)-propanol (0.88 g, 5.0 eq.) and heated at 100° C. under nitrogen overnight. It was cooled to room temperature and concentrated under reduced pressure. The residue was treated with ethyl acetate (10 ml) and treated with saturated NaHCO3 (10 ml). The aqueous layer was extracted with ethyl acetate (2×10 ml), and the combined organic solution was washed with brine (10 ml), and dried with Na2SO4. Solid was filtered off, and the organic solution was concentrated under reduced pressure. 5 ml of ethyl acetate was added to the residue, silica gel was added to form a thick paste, and was concentrated under reduced pressure. This silica gel mixture was loaded onto the Combiflash chromatography and product was eluted using 2N NH3 in MeOH (0-20%)/Ethyl Acetate (100%-80%) gradient to yield 124 mg of product as a light beige solid. It was cooled to room temperature concentrated under reduced pressure The residue was treated with ethyl acetate (10 ml) treated with saturated NaHCO3 (10 ml) The aqueous layer was extracted with ethyl acetate (2×10 ml) the combined organic solution was washed with brine (10 ml) dried with Na2SO4 Solid was filtered off the organic solution was concentrated under reduced pressure 5 ml of ethyl acetate was added to the residue, silica gel was added to form a thick paste was concentrated under reduced pressure was eluted