Br[C:2]1[CH:19]=[CH:18][CH:17]=[CH:16][C:3]=1[CH2:4][CH:5]([CH2:12][CH:13]([CH3:15])[CH3:14])[C:6]([NH:8][CH2:9][C:10]#[N:11])=[O:7].[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][N:30]([C:33]2[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=2)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].C(=O)([O-])[O-].[Na+].[Na+].O>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:10]([CH2:9][NH:8][C:6]([CH:5]([CH2:12][CH:13]([CH3:15])[CH3:14])[CH2:4][C:3]1[CH:16]=[CH:17][CH:18]=[CH:19][C:2]=1[C:36]1[CH:35]=[CH:34][C:33]([N:30]2[CH2:29][CH2:28][N:27]([C:25]([O:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:26])[CH2:32][CH2:31]2)=[CH:38][CH:37]=1)=[O:7])#[N:11]To 2-(2-bromobenzyl)-N-(cyanomethyl)-4-methylpentanamide (260 mg, 0.805 mmol) and 4-[4-(tert-butoxycarbonyl)-1-piperazinyl]phenylboronic acid (275 mg, 0.886 mmol) in DMF (10 mL) under dry nitrogen was added aqueous sodium carbonate (2 M, 1.2 mL, 2.42 mmol) followed by the catalyst PdCl2(dppf) (25 mg, 0.025 mmol). The reaction was heated to 90° C. for 0.5 hours and more PdCl2(dppf) (25 mg, 0.025 mmol) was added and the reaction mixture was heated for another 4 hours. Water was added and the product extracted with ether (2×), dried over Na2SO4, concentrated in vacuo, and purified by flash chromatography over silica gel (EtOAc/Hex, 35/65) to afford tert-butyl 4-[2′-(2-{[(cyanomethyl)amino]carbonyl}-4-methylpentyl)[1,1 ′-biphenyl]-4-yl]-1-piperazinecarboxylate.
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