Reaction SMILES: Br[C:2]1[CH:28]=[CH:27][C:5]2[NH:6][C:7]([C@H:9]3[N:14]4[C:15](=[O:26])[C@@H:16]([NH:21][C:22](=[O:25])[O:23][CH3:24])[CH2:17][CH2:18][C:19](=[O:20])[N:13]4[CH2:12][CH2:11][CH2:10]3)=[N:8][C:4]=2[CH:3]=1.[CH3:29][CH:30]([CH3:64])[C@H:31]([NH:59][C:60](=[O:63])[O:61][CH3:62])[C:32](=[O:58])[N:33]1[CH2:37][CH2:36][CH2:35][C@H:34]1[C:38]1[NH:39][CH:40]=[C:41]([C:43]2[CH:48]=[CH:47][C:46](B3OC(C)(C)C(C)(C)O3)=[CH:45][CH:44]=2)[N:42]=1.C(=O)(O)[O-].[Na+]>COCCOC.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:24][O:23][C:22](=[O:25])[NH:21][C@H:16]1[CH2:17][CH2:18][C:19](=[O:20])[N:13]2[CH2:12][CH2:11][CH2:10][C@@H:9]([C:7]3[NH:8][C:4]4[CH:3]=[CH:2][C:28]([C:46]5[CH:45]=[CH:44][C:43]([C:41]6[NH:42][C:38]([C@@H:34]7[CH2:35][CH2:36][CH2:37][N:33]7[C:32](=[O:58])[C@@H:31]([NH:59][C:60]([O:61][CH3:62])=[O:63])[CH:30]([CH3:64])[CH3:29])=[N:39][CH:40]=6)=[CH:48][CH:47]=5)=[CH:27][C:5]=4[N:6]=3)[N:14]2[C:15]1=[O:26]
Reactant: COC(=O)N[C@H]1CCC(=O)N2CCC[C@@H](c3nc4cc(Br)ccc4[nH]3)N2C1=O
Reactant: COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1nc(-c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)c[nH]1)C(C)C
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])O
Solvent: COCCOC
Product: COC(=O)N[C@H]1CCC(=O)N2CCC[C@@H](c3nc4cc(-c5ccc(-c6cnc([C@@H]7CCCN7C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]6)cc5)ccc4[nH]3)N2C1=O

Procedure:
A solution of methyl (4S,7S)-4-(5-bromo-1H-benzo[d]imidazol-2-yl)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepin-7-ylcarbamate (190 mg, 405 μmol), methyl (S)-3-methyl-1-oxo-1-((S)-2-(4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl)butan-2-ylcarbamate (223 mg, 405 μmol), in 1,2-Dimethoxyethane (6 ml) was treated with sodium bicarbonate (103 mg, 1.22 mmol). The mixture was de-oxygenated by bubbling argon for 15 min. Then, [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium (II) (44.9 mg, 60.8 μmol) was added and the reaction vessel was capped and lowered into a pre-heated oil bath kept at 90° C., and heated for 14 h. The reaction mixture was filtered and concentrated. The residue was taken up in 10% methanol-methylene chloride and washed with water and brine, and dried over MgSO4. The organic layer, upon concentration yielded crude product as brown gum. The crude product was purified on an ISCO Commander machine, using 0-100%-10% methanol-methylene chloridemethylene chloride gradient over 25 min. The product was eluted around 70%-10% methanol-methylene chloridemethylene chloride. {(4S,7S)-4-[5-(4-{2-[(S)-1-((S)-2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-1H-benzoimidazol-2-yl]-6,10-dioxo-octahydro-pyridazino[1,2-a][1,2]diazepin-7-yl}-carbamic acid methyl ester was isolated as sticky brown solid—16.5 mg. This material was dissolved in ethanol (3 mL) and treated with 4N HCl in dioxane (1 mL). The solution was stirred for 10 min. Then, it was concentrated and additional 3 mL of ethanol was added and concentrated again, to yield {(4S,7S)-4-[5-(4-{2-[(S)-1-((S)-2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-1H-benzoimidazol-2-yl]-6,10-dioxo-octahydro-pyridazino[1,2-a][1,2]diazepin-7-yl}-carbamic acid methyl ester dihydrochloride as brown powder (16.5 mg, 4.8%). ESI-LRMS m/e calcd for C38H45N5O7[M+] 739. found 740 [M+H1], 1H NMR (400 MHz, DMSO-d6) δ 8.14 (s, 1H), 7.82-7.98 (m, 5H), 7.65 (br. s. 2H), 7.49-7.59 (m, 2H), 7.33 (d, J=8.03 Hz, 1H), 6.04 (br. s., 1H), 5.11-5.20 (m, 1H), 4.43 (d, J=12.30 Hz, 2H), 4.08-4.18 (m, 2H), 3.89 (m, 2H), 3.69 (dd, J=5.02, 14.56 Hz, 3H), 3.55 (d, J=10.54 Hz, 3H), 3.20 (m, 1H), 2.95 (m, 1H), 2.40 (d, J=6.53 Hz, 1H), 1.82-2.31 (m, 10H), 1.73 (br. s. 1H), 0.71-0.97 (m, 6H).