[N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]=1[CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH2:19][CH3:20])[CH:13]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:28][CH:29]([CH3:31])[CH3:30]>CN(C=O)C>[CH2:19]([O:18][C:14]1[CH:13]=[C:12]([CH2:11][CH2:10][C:2]2[N:3]([CH2:28][CH:29]([CH3:31])[CH3:30])[C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[N:1]=2)[CH:17]=[CH:16][CH:15]=1)[CH3:20]A 50 mL flask fitted with a stir-bar and septum with an Ar inlet was charged with benzimidazole 70 (800 mg, 3.00 mmol) and K2CO3 (829 mg, 6.00 mmol). DMF (10 mL) was added followed by 1-bromo-2-methylpropane (617 mg, 0.489 mL, 4.50 mmol). The mixture was heated in a 90° C. bath overnight. Another 0.5 mL of 1-bromo-2-methylpropane and 300 mg of K2CO3 were added, and the mixture was heated overnight again. A third addition of 0.5 mL of 1-bromo-2-methylpropane and 300 mg of K2CO3 were added. The mixture was heated another 4 hr until complete as monitored by HPLC. The suspension was cooled, and the solids were filtered off and rinsed with EtOAc (60 mL). The filtrate was washed with saturated aqueous NH4Cl (2×50 mL), H2O (2×50 mL), and brine (30 mL), filtered through phase separation paper, and concentrated in vacuo to an orange-brown oil. The crude oil was filtered through a plug of silica gel with CH2Cl2 (2×100 mL) and 5% EtOAc in CH2Cl2 (3×100 mL). The EtOAc/CH2Cl2 filtrates were concentrated to give 670 mg of Compound #16 as a yellow oil (69%). 1H NMR (300 MHz, CDCl3): δ 7.78 (m, 1H), 7.34-7.19 (m, 4H), 6.87-6.76 (m, 3H), 3.98 (qt, 2H), 3.81 (d, 2H), 3.32-3.22 (m, 2H), 3.21-3.11 (m, 2H), 2.17 (nonet, 1H), 1.40 (t, 3H), 0.93 (d, 6H) ppm. HPLC analysis (5:10:85 H2O:A1:MeOH) showed a purity of 99% with a retention time of 5.1 min.
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