Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([C:19]4[CH:20]=[N:21][C:22]([N:25]5[CH2:30][CH2:29][O:28][CH2:27][CH2:26]5)=[CH:23][CH:24]=4)=[CH:15][CH:14]=3)[CH:11]([C:31]3[CH:36]=[CH:35][C:34]([NH:37][C:38](=[O:48])[C@@H:39]([NH:43][C:44](=[O:47])[O:45][CH3:46])[CH:40]([CH3:42])[CH3:41])=[CH:33][CH:32]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH3:49][O:50][C:51]([NH:53][C@@H:54]([CH:65]([CH3:67])[CH3:66])[C:55]([N:57]1[CH2:61][CH2:60][CH2:59][C@H:58]1[C:62](O)=[O:63])=[O:56])=[O:52].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CS(C)=O.CO.CS(C)=O.CO>[CH3:49][O:50][C:51]([NH:53][C@H:54]([C:55]([N:57]1[CH2:61][CH2:60][CH2:59][C@H:58]1[C:62]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:9][CH2:10][C@@H:11]([C:31]3[CH:36]=[CH:35][C:34]([NH:37][C:38](=[O:48])[C@H:39]([CH:40]([CH3:42])[CH3:41])[NH:43][C:44]([O:45][CH3:46])=[O:47])=[CH:33][CH:32]=3)[N:12]2[C:13]2[CH:14]=[CH:15][C:16]([C:19]3[CH:20]=[N:21][C:22]([N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)=[CH:23][CH:24]=3)=[CH:17][CH:18]=2)=[CH:4][CH:3]=1)=[O:63])=[O:56])[CH:65]([CH3:67])[CH3:66])=[O:52]
Reactant: COC(=O)N[C@H](C(=O)Nc1ccc(C2CCC(c3ccc(N)cc3)N2c2ccc(-c3ccc(N4CCOCC4)nc3)cc2)cc1)C(C)C
Reactant: COC(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)O)C(C)C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CO
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)N[C@H](C(=O)Nc1ccc([C@@H]2CC[C@H](c3ccc(NC(=O)[C@@H]4CCCN4C(=O)[C@@H](NC(=O)OC)C(C)C)cc3)N2c2ccc(-c3ccc(N4CCOCC4)nc3)cc2)cc1)C(C)C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
In an oven-dried 5-mL round bottom flask purged with nitrogen, dissolved 3:1 trans/cis mixture of Example 108C (44 mg, 0.068 mmol) and the product of Example 37B (20.31 mg, 0.075 mmol) in anhydrous DMSO (1 mL), added HATU (29.2 mg, 0.075 mmol) and diisopropylethylamine (0.024 mL, 0.136 mmol), and stirred yellow solution at 25° C. for 30 min. Diluted the reaction with MeOH (1 mL) and purified by RP-C18 HPLC (Waters Prep LC, 40 mm Module with Nova Pak HR C18 6 μm 40×100 mm Prep Pak cartridge) eluting with a 30 min gradient of 95:5 0.1% TFA in H2O/AcCN to 25:75 0.1% TFA in H2O/AcCN, then 10 min to 100% AcCN at 20 mL/min. The earlier eluting compound (18.8 mg, 31%) was determined by 1H NMR to be the trans diastereomers. The fractions of the later eluting peak were concentrated by rotary evaporation (water bath 35° C.) to small volume, partitioned between 20% iPrOH/CHCl3 (50 mL) and sat'd aq NaHCO3 (15 mL), separated layers, dried the organic phase over anhydrous MgSO4, filtered, and concentrated by rotary evaporation to afford a 2:3 trans:cis mixture as an off-white solid (10 mg). The mixture was dissolved in 1:1 v/v MeOH/DMSO (1.5 mL) and purified by RP-C18 HPLC (Phenomenex Luna C8(2) 5 μm 100 Å AXIA column (30 mm×75 mm)) eluting with a gradient of 90:10 10 mM NH4OAc:MeOH to 100% MeOH to afford the title cis compounds as a light beige solid (2 mg, 3%). 1H NMR (400 MHz, DMSO-D6) δ ppm 0.85-0.98 (m, 12H), 1.77-2.06 (m, 7H), 2.09-2.21 (m, 1H), 2.36-2.45 (m, 1H), 3.37-3.42 (m, 4H), 3.51 (s, 3H), 3.53 (s, 3H), 3.59-3.70 (m, 6H), 3.75-3.86 (m, 1H), 3.95 (t, J=8.13 Hz, 1H), 4.02 (t, J=8.57 Hz, 1H), 4.44 (dd, J=8.19, 4.72 Hz, 1H), 4.73 (s, 2H), 6.43 (d, J=8.89 Hz, 2H), 6.80 (d, J=8.89 Hz, 1H), 7.27 (d, J=8.78 Hz, 2H), 7.29-7.38 (m, 2H), 7.44 (dd, J=8.57, 2.71 Hz, 4H), 7.54-7.64 (m, 4H), 7.67 (dd, J=8.89, 2.49 Hz, 1H), 8.27 (d, J=2.49 Hz, 1H), 10.04 (s, 2H); MS (ESI+) m/z 903 (M+H)+, 920 (M+NH4)+, 961 (M+AcCN+NH4)+.