IC1C(O)=NC2CCN(C(=O)C(F)(F)F)CC(C)C=2C=1.C(Br)C=C.[CH2:25]([O:28][C:29]1[C:30]([I:47])=[CH:31][C:32]2[CH:38]([CH3:39])[CH2:37][N:36](C(=O)C(F)(F)F)[CH2:35][CH2:34][C:33]=2[N:46]=1)[CH:26]=[CH2:27].C([O-])([O-])=O.[K+].[K+]>CCOC(C)=O.CO.C(Cl)(Cl)Cl>[CH2:25]([O:28][C:29]1[C:30]([I:47])=[CH:31][C:32]2[CH:38]([CH3:39])[CH2:37][NH:36][CH2:35][CH2:34][C:33]=2[N:46]=1)[CH:26]=[CH2:27]A mixture of 3-iodo-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-2-ol (615 mg, 1.54 mmol), allyl bromide (1.33 ml, 15.4 mmol), Ag2CO3 (504 mg, 1.83 mmol) and CHCl3 (35 ml) was stirred under exclusion of light for 4 d at ambient temperature. The reaction mixture was diluted with EtOAc (100 ml) and filtered. The filtrate was concentrated in vacuo and purified by column chromatography rendering 445 mg (66%) of 2-(allyloxy)-3-iodo-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (CDCl3) δ 7.82 (2×s, 1H), 6.18 (dddd, 1H), 5.48 (m, 1H), 5.27 (m, 1H), 4.87 (m, 2H), 4.16-3.01 (m, 7H), 1.32 (2× d, 3H) ppm. A mixture of 2-(allyloxy)-3-iodo-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine (145 mg, 329 μmol), K2CO3 (150 mg) and MeOH (6 ml) was heated for 1 h at 60° C. The reaction mixture was concentrated in vacuo and purified by column chromatography to give 56.3 mg (50%) of 2-(allyloxy)-3-iodo-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (CDCl3) δ 7.78 (s, 1H), 6.08 (dddd, 1H), 5.46 (ddd, 1H), 5.25 (ddd, 1H), 4.86 (m, 2H), 3.20-3.02 (m, 5H), 2.98 (m, 1H), 2.78 (m, 1H), 1.33 (d, 3H) ppm.
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