[C-:1]#[N:2].[K+].[Br:4][C:5]1[C:6]([F:23])=[CH:7][C:8]2[O:14][CH2:13][CH2:12][N:11]3[C:15](I)=[C:16]([C:18]([NH2:20])=[O:19])[N:17]=[C:10]3[C:9]=2[CH:22]=1>CN(C=O)C.[Cu]I>[Br:4][C:5]1[C:6]([F:23])=[CH:7][C:8]2[O:14][CH2:13][CH2:12][N:11]3[C:15]([C:1]#[N:2])=[C:16]([C:18]([NH2:20])=[O:19])[N:17]=[C:10]3[C:9]=2[CH:22]=1Potassium Cyanide (0.8 eq) and Copper (I) Iodide (0.2 eq) were added to solution of 10-bromo-9-fluoro-3-iodo-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide (0.05 g) in DMF (3 ml/mmol). The reaction was heated overnight at 150° C., filtered and purified by reverse phase hplc to give 10-bromo-3-cyano-9-fluoro-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide. This intermediate was reacted with 2-Methyl-3-butyne-ol similar to as described in Procedure E to afford 12 mg of 3-cyano-9-fluoro-10-(3-hydroxy-3-methyl-but-1-ynyl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine-2-carboxamide following reverse phase hplc purification. MS (Q1) 355 (M)+. 1H NMR (400 MHz, DMSO) δ 8.69-8.56 (m, 1H), 8.04 (s, 1H), 7.64 (s, 1H), 7.14-7.00 (m, 1H), 5.51 (d, J=10.2 Hz, 1H), 4.63-4.57 (m, 2H), 4.56-4.49 (m, 2H), 1.49 (s, 6H).
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