[Cl:1][C:2]1[N:7]=[C:6]([CH2:8]Cl)[C:5]([C:10]([O:12]C)=O)=[CH:4][CH:3]=1.Cl.[O:15]1[CH2:18][CH:17]([NH2:19])[CH2:16]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[N:7]=[C:6]2[CH2:8][N:19]([CH:17]3[CH2:18][O:15][CH2:16]3)[C:10](=[O:12])[C:5]2=[CH:4][CH:3]=1Methyl 6-chloro-2-(chloromethyl)pyridine-3-carboxylate (Example 1, Step 4) (0.15 g, 0.68 mmol), oxetan-3-amine hydrochloride (0.15 g, 1.36 mmol) and potassium carbonate (0.38 g, 2.7 mmol) were stirred in DMF (10 mL) at room temperature overnight. Water and ethyl acetate were added and the biphasic mixture was extracted with ethyl acetate (2×). The combined organic extracts were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. Purification of the residue by silica gel chromatography (6-50% EtOAc/hexanes) gave the title compound as a white solid.
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