[Br:1][C:2]1[C:3]([CH2:8][OH:9])=[N:4][CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[I:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=1O.CC(C)([O-])C.[Na+]>O1CCCC1.ClCCl>[Br:1][C:2]1[C:3]([CH2:8][O:9][C:28]2[CH:27]=[C:26]([Cl:29])[CH:25]=[CH:24][C:23]=2[I:22])=[N:4][CH:5]=[CH:6][CH:7]=1(3-Bromo-pyridin-2-yl)-methanol (7.39 g, 39.30 mmoles), and triethylamine (7.15 mL, 51.3 mmoles) are combined in tetrahydrofuran (70 mL) under nitrogen. The solution is chilled to 0.6° C. with an ice bath. Methanesulfonyl chloride (3.35 mL, 43.28 mmol) is added dropwise over 20 min, controlling the exotherm such that the internal temperature does not exceed 5° C. Following the addition, the reaction is stirred over an ice bath. After 20 min HPLC analysis shows that the (3-Bromo-pyridin-2-yl)-methanol is fully consumed. Triethylamine hydrochloride is filtered using a fitted glass funnel, washing with cold THF (50 mL). The THF filtrate containing the mesylate is placed under nitrogen and chilled in an ice bath. 2-Iodo-5-chlorophenol (10.00 g, 39.30 mmoles) is added, followed by addition of sodium t-butoxide (4.10 g, 41.38 mmol) in two equal portions with a mild exotherm of about 5° C. for each addition. The ice bath is removed and the reaction allowed to stir overnight. The reaction is quenched with water (50 mL) and the lower aqueous layer allowed to slowly separate. The organic portion is washed with brine (25 mL), and then the brine and aqueous portions back-extracted with THF (10 mL). The organic portions are combined and dried over sodium sulfate, filtered, and concentrated to afford a rusty orange solid. The solid is dissolved in dichloromethane (25 mL) and chromatographed on an AnaLogix Inc., Intelliflash 180 automated chromatography instrument, version 1.8.0. using a gradient of 10- 20% ethyl acetate/hexanes over 35 min to afford 11.0 g (65%) of the product as a yellow solid. 1H NMR (DMSO) δ 5.31 (2H, s), 6.85 (1H, dd), 7.25 (1H, m), 7.39 (1H, dd), 7.77 (1H, d), 8.17 (1H, d), 8.59 (1H, d).
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