[N:1]1[C:5]2[CH2:6][CH2:7][O:8][CH2:9][C:4]=2[S:3][C:2]=1[NH2:10].[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([O:21][CH3:22])=[C:16]([CH:20]=1)[C:17](O)=[O:18].ON1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.Cl.C(N(CC)CC)C>O1CCCC1.CN(C)C=O.CCOC(C)=O>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([O:21][CH3:22])=[C:16]([CH:20]=1)[C:17](/[N:10]=[C:2]1\[S:3][C:4]2[CH2:9][O:8][CH2:7][CH2:6][C:5]=2[NH:1]\1)=[O:18]To a solution of commercially available 6,7-dihydro-4H-pyrano[4,3-d]thiazol-2-amine (1.73 g, 11.1 mmol, JW-Pharmalab) in tetrahydrofuran/N,N-dimethylformamide (5:1, 60 mL) were added 5-chloro-2-methoxybenzoic acid (2.27 g, 12.2 mmol, Aldrich), 1-hydroxybenzotriazole (1.9 g, 12.2 mmol, Aldrich), N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (2.3 g, 12.2 mmol, Aldrich) and triethylamine (4.6 ml, 33.2 mmol). After stirring at 60° C. for 16 h, the reaction mixture was cooled, diluted with EtOAc (50 mL) and quenched with saturated NaHCO3 (50 mL). The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic extracts were washed with brine (50 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix® Intelliflash280 ™ (SiO2, 0-5% methanol in methylene chloride). MS (ESI+) m/z 325 (M+H)+.
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