[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=1.[O:11]1[CH2:16][CH2:15][CH:14]([CH2:17][NH2:18])[CH2:13][CH2:12]1.C(Cl)CCl.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C.CCOC(C)=O>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:18][CH2:17][CH:14]2[CH2:15][CH2:16][O:11][CH2:12][CH2:13]2)=[O:8])=[CH:4][N:3]=1Combined 6-chloronicotinic acid (2.0 g, 12.69 mmol), (tetrahydro-2H-pyran-4-yl)methanamine (2.193 g, 19.04 mmol) and EDC (4.87 g, 25.4 mmol) in CH2Cl2 (100 mL) then added Hunig's base (6.65 mL, 38.1 mmol) and the mixture stirred at 20° C. for 24 h. More (tetrahydro-2H-pyran-4-yl)methanamine (1 g, 0.7 equiv), Hunig's base (2.2 mL, 1 equiv.) and DMAP (ca. 10 mg) were added and the reaction was heated at 45° C. for 18 h. More Hunig's base (3 mL) and DMAP (80 mg) was added and heating continued at 50° C. for 5 h. The reaction was then concentrated in vacuo to give a residue which was taken up in EtOAc (100 mL) and washed with saturated aqueous ammonium chloride (100 mL) and brine, dried over magnesium sulfate and concentrated in vacuo to give a residue which was purified on an 80 g silica gel column eluted with 0 to 100% EtOAc in hexanes, then filtered and dried in the lyophilizer to give the title compound (0.985 g, 30.5% yield) as a white solid. MS m/z 255, 257 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.12-1.28 (m, 2 H) 1.60 (dd, J=12.9, 1.8 Hz, 2 H) 1.78 (td, J=7.4, 3.7 Hz, 1 H) 3.13-3.20 (m, 2 H) 3.26 (td, J=11.7, 2.1 Hz, 2 H) 3.84 (dd, J=11.4, 2.5 Hz, 2 H) 7.64 (dd, J=8.3, 0.5 Hz, 1 H) 8.23 (dd, J=8.3, 2.5 Hz, 1 H) 8.74 (t, J=5.6 Hz, 1 H) 8.82 (dd, J=2.5, 0.8 Hz, 1 H).
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