Reaction Steps
(5-tert-Butyl-2-methyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester (US 2004/0192653, which is incorporated herein by reference in its entirety; 17 mg, 0.051 mmol) was treated with a solution of Intermediate 13e (25 mg, 0.047 mmol) in 1,4-dioxane (0.4 mL) then DIPEA (10 μL, 0.058 mmol) was added. The mixture was stirred at 70° C. overnight. The mixture was treated with another portion of (5-tert-butyl-2-methyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloro-ethyl ester (7.8 mg, 0.024 mmol) in 1,4-dioxane (0.1 mL) and stirred at 70° C. for 6 h. The mixture was evaporated in vacuo and the residue was partitioned between DCM and water. The aqueous layer was then extracted with DCM (2×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by HPLC in 4 portions (Method 6, 5-95% MeCN in H2O, 0.1% HCO2H over 30 min), and the isolated product triturated (diethyl ether) to give a solid. The solid was collected by filtration, washed with ether and dried at 50° C. in vacuo to give the title compound. (5.4 mg, 16%). LCMS (Method 5): Rt 3.27 min, m/z 716.3 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.20 (9H, s), 1.82-1.99 (2H, m), 1.99-2.05 (1H, m), 2.05-2.14 (1H, m), 2.18 (3H, s), 2.29-2.42 (4H, br s), 2.42-2.52 (4H, br s, partially obscured by DMSO), 3.56 (3H, s, partially obscured by water), 3.60 (2H, s, partially obscured by water), 4.79-4.88 (1H, m), 5.54 (1H, t, J=4.3 Hz), 6.01 (1H, s), 6.91 (1H, d, J=8.4 Hz), 7.23-7.30 (1H, m), 7.33-7.39 (4H, m), 7.66 (2H, s), 7.91 (1H, d, J=10.2 Hz), 7.97 (1H, d, J=1.7 Hz), 8.21 (1H, s), 8.29 (1H, s).
