[CH3:1][NH2:2].[CH3:3][C:4]1([CH3:19])[C:8](=O)[CH2:7][CH:6]([C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][C:11]=2[F:18])[CH2:5]1.O.[NH2:21]N.C(O)(=O)C>C(O)(C)C>[CH3:3][C:4]1([CH3:19])[C:8]2[NH:21][N:2]=[CH:1][C:7]=2[CH:6]([C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][C:11]=2[F:18])[CH2:5]1Methanamine, 1,1-dimethoxy-N,N-dimethyl-(42.05 g, 352.84 mmol) is added to 4-(3,3-dimethyl-4-oxo-cyclopentyl)-3-fluoro-benzonitrile (34 g, 117.61 mmol) and the mixture is stirred at 90° C. for 16 hours. The mixture is cooled to ambient temperature and the excess DMF-DMA is evaporated to dryness. To the crude residue is added: isopropyl alcohol (163.20 mL), hydrazine monohydrate (11.78 g. 235.22 mmol), and acetic acid (20.22 mL, 352.84 mmol) and the mixture is stirred at 70° C. for 2 hours. The mixture is cooled to ambient temperature and the solvent evaporated to dryness. The mixture is poured into water (200 mL) and is extracted with MTBE (2×200 mL). The mixture is washed with brine, dried over MgSO4, filtered, and concentrated to dryness. The residue is purified by silica gel flash chromatography, eluting with hexane and 10% IPA to give the title compound (30 g, 99%). ES/MS (m/z) 256 (M+1), 1H NMR (300.16 MHz, DMSO) δ 12.62-12.60 (m, 1H), 7.82 (dd, J=1.5, 10.2 Hz, 1H), 7.62 (dd, J=1.5, 8.1 Hz, 1H), 7.42-7.34 (m, 1H), 4.52 (t, J=7.7 Hz, 1H), 2.73 (d, J=1.8 Hz, 1H), 2.07 (dd, J=8.1, 11.7 Hz, 1H), 1.25 (s, 6H).
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