Reaction Steps
A solution of 1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-ylamine (Intermediate 4, 708.7 mg, 3.59 mmol) in N,N-dimethylformamide was added to 2-(4-iodo-6-oxo-6H-pyridazin-1-yl)-4-methyl-pentanoic acid (Intermediate 86, 1.42 g, 4.23 mmol). At this point, the reaction was treated with 4-dimethylaminopyridine (21.9 mg, 0.18 mmol) followed by N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (823.7 mg, 4.31 mmol). The resulting reaction was stirred at 25° C. overnight. The reaction was then diluted with ethyl acetate (200 mL), was washed with water (200 mL) and a saturated aqueous sodium chloride solution (200 mL), filtered, and concentrated in vacuo onto silica gel. Chromatography (ISCO Combiflash, 10-60% ethyl acetate/hexanes) afforded 2-(4-iodo-6-oxo-6H-pyridazin-1-yl)-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide as a white/yellow solid (950 mg, 51%); ES+-HRMS m/e calcd for C19H26N5O4I [M+Na+] 538.0921, found 538.0921. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.83 (d, J=5.7 Hz, 3H), 0.85 (d, J=5.7 Hz, 3H), 1.23 (s, 3H), 1.29 (s, 3H), 1.35 (br. s., 1H), 1.76 (ddd, J=13.3, 9.4, 4.2 Hz, 1H), 2.03-2.21 (m, 1H), 3.71 (dd, J=8.4, 6.0 Hz, 1H), 3.98 (dd, J=8.4, 6.5 Hz, 1H), 4.03-4.18 (m, 2H), 4.33 (quin, J=6.0 Hz, 1H), 5.47 (dd, J=11.0, 4.1 Hz, 1H), 6.36 (d, J=2.1 Hz, 1H), 7.58 (d, J=1.8 Hz, 1H), 7.59 (d, J=2.1 Hz, 1H), 8.23 (d, J=1.8 Hz, 1H), 10.82 (s, 1H).
