[H-].[Na+].[I:3][C:4]1[CH:5]=[N:6][NH:7][CH:8]=1.CS(O[CH:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)(=O)=O.O>CN(C=O)C>[O:17]1[CH2:18][CH2:19][CH:14]([N:6]2[CH:5]=[C:4]([I:3])[CH:8]=[N:7]2)[CH2:15][CH2:16]1As shown in step 2-ii of Scheme 2, sodium hydride (6.101 mL of 60% NaH/mineral oil, 137.3 mmol) was added slowly to a solution of 4-iodopyrazole (24.21 g, 124.8 mmol) in 200 mL of anhydrous DMF at 0° C. The solution was stirred for 1 hour at 0° C. and tetrahydro-2H-pyran-4-yl methanesulfonate (Compound 1010, 22.5 g, 124.8 mmol) in 100 mL of anhydrous DMF was added dropwise. The reaction mixture was heated at 100° C. for 18 hours, at which time an additional 8.0 g of (Compound 1010) in 25 mL of anhydrous DMF was added dropwise. The reaction mixture was heated at 100° C. for an additional 24 hours. The mixture was cooled to room temperature and 100 mL of water was added. The mixture was extracted with EtOAc (3×100 mL) and the combined organics were washed with water, washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford a semi-solid. Recrystallization from DCM yielded 1-(tetrahydro-2H-pyran-4-yl)-4-iodo-1H-pyrazole (Compound 1011, 11.96 g). A second crop of crystals was obtained upon trituration of the mother liquor with hexanes (5.26 g, 49.6% total yield): ESMS (M+H)=279.0.
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