[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[N:12]=[CH:11][C:10](/[CH:13]=[CH:14]/[C:15]([OH:17])=O)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.C(N(CC)CC)C.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.[NH2:52][C:53]1[CH:58]=[C:57]([C:59]2[S:60][CH:61]=[CH:62][CH:63]=2)[CH:56]=[CH:55][C:54]=1[NH:64][C:65](=[O:71])[O:66][C:67]([CH3:70])([CH3:69])[CH3:68]>CN(C=O)C.CN(C)C1C=CN=CC=1>[O:1]1[CH2:2][CH2:3][N:4]([C:7]2[N:12]=[CH:11][C:10](/[CH:13]=[CH:14]/[C:15]([NH:52][C:53]3[CH:58]=[C:57]([C:59]4[S:60][CH:61]=[CH:62][CH:63]=4)[CH:56]=[CH:55][C:54]=3[NH:64][C:65](=[O:71])[O:66][C:67]([CH3:69])([CH3:68])[CH3:70])=[O:17])=[CH:9][CH:8]=2)[CH2:5][CH2:6]1To a solution of 164 (0.275 g, 1.17 mmol) in DMF (10 mL) was added triethylamine (0.168 mL, 1.21 mmol) and BOP reagent (0.563 g, 1.27 mmol) and the mixture was stirred at room temperature for 30 min. Then amine 4 (0.309 g, 1.06 mmol) and excess triethylamine (0.443 mL, 3.18 mmol) were added and the reaction mixture was allowed to stir for 18 h at room temperature. Then 4-(dimethylamino)pyridine (catalytic amount) was added and the reaction mixture was heated to 50-60° C. for 24 h. The solution was concentrated, diluted with AcOEt, washed with saturated NaHCO3, H2O, brine, dried over MgSO4, filtered and concentrated. The resulting yellow solid was triturated from ethyl ether to give compound 165 (0.435 g, 81% yield).
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