C(NC(C)C)(C)C.C([Li])CCC.[Br:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][N:15]=1.[C:21]12([CH2:31][N:32]=[C:33]=[O:34])[CH2:30][CH:25]3[CH2:26][CH:27]([CH2:29][CH:23]([CH2:24]3)[CH2:22]1)[CH2:28]2.Cl>O1CCCC1.CCCCCC>[C:21]12([CH2:31][NH:32][C:33](=[O:34])[C:18]3[C:17]([Cl:20])=[CH:16][N:15]=[C:14]([Br:13])[CH:19]=3)[CH2:30][CH:25]3[CH2:26][CH:27]([CH2:29][CH:23]([CH2:24]3)[CH2:22]1)[CH2:28]2To a stirred solution of di-isopropylamine (2.1 ml) in anhydrous tetrahydrofuran (15 ml) at is −5° C. was added, dropwise a solution of n-butyl lithium in hexane (2.5 molar, 4.8 ml) and the resulting solution was stirred for 30 minutes and was then cooled to −70° C. To the cooled solution was added a solution of 2-bromo-5-chloropyridine (2.39 g) in anhydrous tetrahydrofuran (10 ml) maintaining the internal temperature of the reaction below −65° C. The reaction was maintained at −70° C. for 15 minutes and then a solution of 1-adamantylmethyl isocyanate (1.91 g) in anhydrous tetrahydrofuran (5 ml) was dropwise added (care exotherm). The mixture was stirred for 10 minutes and was then poured into a solution of 1M aqueous hydrochloric acid solution (50 ml) and the mixture extracted into ethyl acetate (3×25 ml). The combined extracts were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by chromatography on silica gel eluting with ethyl acetate:iso-hexane (1:9 to 1:4 to 1:1) to afford the sub-titled compound (2.70 g) as a white solid.
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