[Cl:1][C:2]1[C:16]([N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[CH:15][C:5]2[N:6]([CH2:9][O:10][CH2:11][CH2:12][O:13][CH3:14])[CH:7]=[N:8][C:4]=2[CH:3]=1.C([N-]C(C)C)(C)C.[Li+].[Cl:30]N1C(=O)CCC1=O.[NH4+].[Cl-]>C1COCC1>[Cl:30][C:7]1[N:6]([CH2:9][O:10][CH2:11][CH2:12][O:13][CH3:14])[C:5]2[CH:15]=[C:16]([N:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)[C:2]([Cl:1])=[CH:3][C:4]=2[N:8]=1
A solution of 5-chloro-1-(2-methoxy-ethoxymethyl)-6-pyrrolidin-1-yl-1H-benzoimidazole (0.221 g, 0.714 mmol) and THF (2.5 mL) was cooled to −78° C. in an acetone/dry ice bath. Lithium diisopropylamide (2.0M solution in THF/heptane/ethylbenzene, 0.90 mL, 1.8 mmol) was added dropwise and the reaction mixture was stirred at −78° C. for 30 min. N-chlorosuccinimide (267 mg, 2.00 mmol) was added at −78° C. and the reaction mixture was warmed to 23° C. and stirred for 2 h. Saturated aqueous NH4Cl (20 mL) was added and the crude product was extracted into EtOAc (3×50 mL). The combined organic layers were washed with brine (50 mL), dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) (0-100% EtOAc/hexanes) to yield the titled compound (0.240 g, 71%) as a mixture of regioisomers with purity of 70%. MS (ESI/CI): mass calcd. for C15H19Cl2N3O2, 343.1; m/z found, 344.1 [M+H]+.
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