Br[C:2]1[N:3]([CH2:7][C:8]2[CH:9]=[C:10]([C:14]3[CH:18]=[C:17]([CH2:19][CH:20]([CH3:22])[CH3:21])[S:16][C:15]=3[S:23]([NH:26]C(C)(C)C)(=[O:25])=[O:24])[CH:11]=[CH:12][CH:13]=2)[CH:4]=[CH:5][N:6]=1.C1(OC)C=CC=CC=1.N1(C2C=CC=CN=2)[CH2:43][CH2:42][CH2:41][CH2:40]1.[Cl:50]C(OCCCC)=O.C(O)(=O)CC(CC(O)=O)([C:62]([OH:64])=[O:63])O>C(O)(C(F)(F)F)=O>[CH2:40]([O:64][C:62]([NH:26][S:23]([C:15]1[S:16][C:17]([CH2:19][CH:20]([CH3:21])[CH3:22])=[CH:18][C:14]=1[C:10]1[CH:11]=[CH:12][CH:13]=[C:8]([CH2:7][N:3]2[CH:4]=[CH:5][N:6]=[C:2]2[Cl:50])[CH:9]=1)(=[O:24])=[O:25])=[O:63])[CH2:41][CH2:42][CH3:43]To a solution of 3-[3-(2-bromoimidazol-1-ylmethyl)phenyl]-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide (44.1 mg, 0.086 mmol; see step (b)) in TFA (3 mL) was added anisole (150 μL) and the reaction mixture was stirred overnight at ambient temperature. The reaction mixture was concentrated in vacuo and dried in vacuo overnight. To the crude product dissolved in pyridine (1.5 mL) was added pyrrolidinopyridine (25.6 mg, 0.173 mmol) and butyl chloroformate (109.9 μL, 0.846 mmol) and the reaction mixture was stirred for 36 h. Citric acid (3 mL, 10% aq) was added to the reaction mixture, which was then extracted with EtOAc, dried (over anhydrous MgSO4), concentrated in vacuo, and the residue purified by flash chromatography using MeOH:CH2Cl2 (5:95) as eluent to give the title compound in 57% yield, over two steps, (25 mg, 0.049 mmol).
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