[C:1]([C:3]1[CH:18]=[CH:17][C:6]([CH2:7][N:8]2[C:12]([CH2:13][C:14]([O-:16])=O)=[CH:11][N:10]=[CH:9]2)=[CH:5][C:4]=1[F:19])#[N:2].[Li+].Cl.[NH2:22][C@@H:23]1[CH2:27][CH2:26][N:25]([C:28]2[C:37]3[C:32](=[CH:33][CH:34]=[C:35]([OH:38])[CH:36]=3)[CH:31]=[CH:30][CH:29]=2)[C:24]1=[O:39].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.C(N(CC)C(C)C)(C)C>CN(C=O)C>[C:1]([C:3]1[CH:18]=[CH:17][C:6]([CH2:7][N:8]2[C:12]([CH2:13][C:14]([NH:22][C@@H:23]3[CH2:27][CH2:26][N:25]([C:28]4[C:37]5[C:32](=[CH:33][CH:34]=[C:35]([OH:38])[CH:36]=5)[CH:31]=[CH:30][CH:29]=4)[C:24]3=[O:39])=[O:16])=[CH:11][N:10]=[CH:9]2)=[CH:5][C:4]=1[F:19])#[N:2]A mixture of lithium [1-(4-cyano-3-fluorobenzyl)-1H-imidazol-5-yl]acetate, as described above in Step D, (46 mg, 0.18 mmol), (R)-3-amino-1-(7-hydroxynaphthalen-1-yl)-2-oxopyrrolidine hydrochloride, as described in Example 10A (45 mg, 0.16 mmol), HOBT (24 mg, 0.18 mmol), EDC (35 mg, 0.18 mmol), and N,N-diisopropylethylamine (0.084 mL, 0.48 mmol) was stirred in DMF (1 mL) at ambient temperature for 18 hours. The solvent was removed under reduced pressure and the residue was partitioned between saturated aqueous NaHCO3 (1 mL) and CHCl3 (2 mL). The aqueous layer was extracted further with CHCl3 (2×2 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography on silica, eluting with a gradient of EtOAc—10% MeOH—1% NH4OH to EtOAc—15% MeOH—1.5% NH4OH to yield the titled product as a white solid.
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