[I:1][C:2]1[C:3]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[N:4][NH:5][C:6]=1[CH3:7].[O:13]1[CH:18]=[CH:17][CH2:16][CH2:15][CH2:14]1.C1(C)C=CC(S(O)(=O)=O)=CC=1>O1CCCC1>[I:1][C:2]1[C:3]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[N:4][N:5]([CH:14]2[CH2:15][CH2:16][CH2:17][CH2:18][O:13]2)[C:6]=1[CH3:7]A solution of ethyl 4-iodo-5-methyl-1H-pyrazole-3-carboxylate (3.6 g, 12.85 mmol, 1.00 equiv), 3,4-dihydro-2H-pyran (3.24 g, 38.52 mmol, 3.00 equiv) and p-toluenesulfonic acid (222 mg, 1.29 mmol, 0.10 equiv) in tetrahydrofuran (150 mL) was stirred at 80° C. for 8 h. The resulting mixture was concentrated under vacuum and the residue was mixed with 100 mL of H2O. The resulting mixture was extracted with 2×50 mL of ethyl acetate. The combined organic layers were washed with 2×100 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with 0-30% of ethyl acetate in petroleum ether to yield 4.4 g (94%) of (R/S) ethyl 4-iodo-5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole-3-carboxylate as a yellow solid. 1H-NMR (300 MHz, CDCl3): δ 5.43 (dd, J=9.9 Hz, 2.7 Hz, 1H), 4.40 (q, J=7.2 Hz, 2H), 4.05-4.00 (m, 1H), 3.67-3.60 (m, 1H), 2.43 (s, 3H), 2.12-2.10 (m, 1H), 1.96-1.95 (m, 1H), 1.69-1.58 (m, 4H), 1.40 (t, J=7.2 Hz, 3H) ppm. LCMS (method D, ESI): RT=1.53 min, m/z=365.0 [M+H]+.
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