N1([C:6](N2C=CN=C2)=[O:7])C=CN=C1.[I:13][C:14]1[CH:15]=[N:16][N:17]([CH:19]2[CH2:24][CH2:23][CH:22]([NH:25][CH2:26][CH2:27][OH:28])[CH2:21][CH2:20]2)[CH:18]=1.Cl>CN(C)C1C=CN=CC=1.C(Cl)(Cl)Cl>[I:13][C:14]1[CH:15]=[N:16][N:17]([C@H:19]2[CH2:20][CH2:21][C@H:22]([N:25]3[CH2:26][CH2:27][O:28][C:6]3=[O:7])[CH2:23][CH2:24]2)[CH:18]=1Di-imidazol-1-yl-methanone (1.32 g; 8.14 mmol; 2.9 eq.) was added in one portion to a solution of 2-[4-(4-Iodo-pyrazol-1-yl)-cyclohexylamino]-ethanol (intermediate 25; 997 mg; 2.83 mmol; 1.0 eq.) and Dimethyl-pyridin-4-yl-amine (60 mg; 0.49 mmol; 0.17 eq.) in CHCl3 (30 mL). The reaction suspension was heated at 60° C. for 20 min then cooled and poured into a 1 N HCl solution. It was extracted with DCM (twice), combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography on silica (DCM: MeOH; 96:4) followed by a trituration in Acetonitrile afforded the title compound as a white solid (239 mg; 23%). 1H NMR (300 MHz, DMSO) δ 7.96 (d, J=0.5 Hz, 1H), 7.51 (d, J=0.5 Hz, 1H), 4.30-4.12 (m, 3H), 3.63-3.46 (m, 3H), 2.11-2.00 (m, 2H), 1.91-1.58 (m, 6H). HPLC (Condition A): Rt 2.98 min (purity 99.0%). MS (ESI+): 362.2.
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