Cl.[CH3:2][C:3]1[CH:8]=[C:7]([C:9]([N:11]2[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[CH2:15][N:14]3[C:22]([C:25]([N:27]4[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]4)=[O:26])=[CH:23][CH:24]=[C:13]3[CH2:12]2)=[O:10])[CH:6]=[CH:5][C:4]=1[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[C:39]([F:42])([F:41])[F:40].C(N(CC)C(C)C)(C)C.[CH3:52][O:53][CH2:54][C@@H:55]1[O:57][CH2:56]1>CO>[CH3:52][O:53][CH2:54][C@H:55]([OH:57])[CH2:56][N:30]1[CH2:29][CH2:28][N:27]([C:25]([C:22]2[N:14]3[C:13]([CH2:12][N:11]([C:9]([C:7]4[CH:6]=[CH:5][C:4]([C:33]5[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=5[C:39]([F:40])([F:42])[F:41])=[C:3]([CH3:2])[CH:8]=4)=[O:10])[C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=4[CH2:15]3)=[CH:24][CH:23]=2)=[O:26])[CH2:32][CH2:31]1To a solution of 10,11-dihydro-10-[[2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl]-3-(1-piperazinylcarbonyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine hydrochloride salt of Example 5, Step B (0.50 g, 0.84 mmol) and N,N-diisopropylethyl amine (0.16 mL, 0.92 mmol) in methanol (5 mL) was added (R)-(−)-glycidyl methyl ether (0.11 mL, 1.22 mmol). The reaction mixture was heated to 60° C. overnight then cooled and concentrated in vacuo. The residue was partitioned between dichloromethane and water. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a white foam. Purification by flash chromatography on silica gel using a solvent system of 3% methanol in chloroform provided 0.40 g of title product as a white foam.
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