The compound (2-amino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (1.8 g, 6.6 mmol, see procedure 4a) was dissolved in 32 mL of 2:1 CH2Cl2/DMF. The resultant solution was charged sequentially with mono-benzyl malonate (1.28 g, 6.6 mmol), N,N-diisopropylethylamine (5.8 mL, 33 mmol) and HATU (3.0 g, 7.9 mmol). The mixture was stirred for 12 h at RT, concentrated in vacuo, and partitioned between EtOAc and sat. NH4Cl. The aqueous phase was extracted with EtOAc (1×). The combined organic extracts were washed with sat. NaHCO3 and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography to provide N-(2-tert-butoxycarbonylamino-5-trifluoromethyl-phenyl)-malonamic acid benzyl ester (2.3 g, 77% yield). A portion (860 mg) of this material was dissolved in 10 mL of THF. The resultant solution was charged with 30 mL of acetic acid, heated at 65° C. for 3 h, and concentrated in vacuo. The residue was purified by flash chromatography to provide (5-trifluoromethyl-1H-benzoimidazol-2-yl)-acetic acid benzyl ester (343 mg, 54% yield). MS found: (M+H)+=335.2. (29b) The compound (5-trifluoromethyl-1H-benzoimidazol-2-yl)-acetic acid benzyl ester (105 mg, 0.32 mmol) was dissolved in THF (3.6 mL). The resultant solution was charged sequentially with MeOH (1.2 mL) and aq. LiOH (15 mg LiOH in 1.2 mL water), stirred for 12 h at RT, and concentrated in vacuo (the water bath was left unheated) to provide the lithium salt of (5-trifluoromethyl-1H-benzoimidazol-2-yl)-acetic acid. This material was incorporated into procedure 28b in the place of the lithium salt of (4-trifluoromethyl-1H-benzoimidazol-2-yl)-acetic acid. The resultant product was carried through procedure 28c to provide the title compound as a white powder after reverse-phase HPLC purification and lyopholization. MS found: (M+H)+=477.5.
