C([O:3][C:4](=[O:51])[CH:5]([NH:33][S:34]([N:37]1[CH2:42][CH2:41][N:40]([CH2:43][C:44]2[CH:49]=[CH:48][C:47]([CH3:50])=[CH:46][CH:45]=2)[CH2:39][CH2:38]1)(=[O:36])=[O:35])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:17]=[C:16]([C:18]3[CH:23]=[CH:22][C:21]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[CH:20][CH:19]=3)[O:15][N:14]=2)=[C:9]([F:32])[CH:8]=1)C.CC1C=CC(CN2CCNCC2)=CC=1.C(N(CC)CC)C>C(#N)C>[C:28]([O:27][C:25]([NH:24][C:21]1[CH:22]=[CH:23][C:18]([C:16]2[O:15][N:14]=[C:13]([C:10]3[CH:11]=[CH:12][C:7]([CH2:6][CH:5]([NH:33][S:34]([N:37]4[CH2:38][CH2:39][N:40]([CH2:43][C:44]5[CH:49]=[CH:48][C:47]([CH3:50])=[CH:46][CH:45]=5)[CH2:41][CH2:42]4)(=[O:35])=[O:36])[C:4]([OH:51])=[O:3])=[CH:8][C:9]=3[F:32])[N:17]=2)=[CH:19][CH:20]=1)=[O:26])([CH3:31])([CH3:30])[CH3:29]3-{4-[5-(4-tert-Butoxycarbonylamino-phenyl)-[1,2,4]oxadiazol-3-yl]-3-fluoro-phenyl}-2-[4-(4-methyl-benzyl)-piperazine-1-sulfonylamino]-propionic acid ethyl ester. A mixture of oxazolidione from Step A (40 mg, 0.065 mmol), 1-(4-methylbenzyl)piperazine (24.7 mg, 0.13 mmol), and triethylamine (20 mg, 0.2 mmol) in acetonitrile (3 mL) was heated at 85° C. for 2.5 hrs. TLC showed the reaction was completed. The solution was concentrated. Ethyl acetate (20 mL) and 1N aq. HCl solution (10 mL) were added to the solution. The layers were separated, and the aqueous portion was extracted with ethyl acetate (20 mL). The combined organic layer was washed with brine (2×20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated to give the title compound (32 mg, 69% yield) as a yellow solid.
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