Reaction Steps
A suspension of tert-butyl [1-benzyl-2-({2-chloro-6-[(methylsulfonyl)(propyl)amino]pyridin-4-yl}methoxy)-1-methylethyl]carbamate (115 mg, 0.22 mmol, intermediate VI), sodium carbonate (70 mg, 0.66 mmol), PdCl2(PhCN)2 (2 mg, 0.004 mmol), 4A sieves and 1-[2-(dicyclohexylphasphanyl)ferrocenyl]ethyldicyclohexylphosphane (11 mg, 0.017 mmol, STREM) in n-butanol (2 ml, degassed with Argon), was purged with CO and stirred at 100° C. for 16 h under 1 atm of CO. The reaction mixture was diluted with dichloromethane, washed with water and brine, dried over sodium sulfate, concentrated in vacuo, azeothroped with toluene, and purified by flash chromatography (silica, 0-35% EtOAc/hexanes) to provide butyl 4-({2-[(tert-butoxycarbonyl)amino]-2-methyl-3-phenylpropoxy}methyl)-6-[(methylsulfonyl)(propyl)amino]pyridine-2-carboxylate as a yellow oil which was dissolved in 1:1 THF:MeOH (1.6 mL) and treated with aq LiOH (0.38 mL, 0.38 mmol, 1N) for 2 h at rt. The reaction mixture was acidified to pH 3-4 with 1N HCl, extracted with dichloromethane, dried over sodium sulfate, concentrated in vacuo, azeothroped with toluene to give 4-({2-[(tert-butoxycarbonyl)amino]-2-methyl-3-phenylpropoxy}methyl)-6-[(methylsulfonyl)(propyl)amino]pyridine-2-carboxylic acid as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.03 (s, 1H), 7.71 (s, 1H), 7.34-7.13 (m, 5H), 4.67 (s, 2H), 4.49 (s, 1H), 3.93 (t, J=7.6 Hz, 2H), 3.72 (A of AB, d, J=9.2 Hz, 1H), 3.62 (B of AB, d, J=9.2 Hz, 1H), 3.17 (A of AB, d, J=13.6 Hz, 1H), 3.05 (s, 3H), 2.90 (13 of AB, d, J=13.6 Hz, 1H), 1.70-1.55 (m, 2H), 1.46 (s, 9H), 1.27 (s, 3H), 0.96 (t, J=7.6 Hz, 3H).
