[I:1][C:2]1[C:7]([C:8]([OH:10])=O)=[C:6]([O:11][CH3:12])[N:5]=[CH:4][CH:3]=1.Cl.Cl.[O:15]1[CH2:20][CH2:19][CH2:18][CH:17]([NH:21][NH2:22])[CH2:16]1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.O>[I:1][C:2]1[C:7]([C:8]([NH:22][NH:21][CH:17]2[CH2:18][CH2:19][CH2:20][O:15][CH2:16]2)=[O:10])=[C:6]([O:11][CH3:12])[N:5]=[CH:4][CH:3]=1A solution of 4-iodo-2-methoxynicotinic acid (3.0 g) obtained in Step C of Example 6, tetrahydro-2H-pyran-3-ylhydrazine dihydrochloride (2.44 g), DIEA (5.63 mL), EDCI hydrochloride (2.47 g) and HOBt (1.74 g) in DMF (50 mL) was stirred overnight at room temperature. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (2.36 g).
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