To a refluxing solution of (R)-7-cyano-2,3,4,5-tetrahydro-4-(phenylacetyl)-3-(phenylmethyl)-1H-1,4-benzodiazepine (prepared from Compound C of Example 248 by EDC/HOAt coupling with phenylacetic acid, 0.100 g, 0.26 mmol) and 4-formylimidazole (0.025 g, 0.26 mmol) in AcOH (0.3 mL) and dichloroethane (0.5 mL) with 3 A sieves was added sodium triacetoxyborohydride (0.055 g, 0.26 mmol). The mixture was stirred 16 hr, and then for 3 days, with additional aldehyde and sodium triacetoxyborohydride (3×1 eq each) added each day. The mixture was diluted with CHCl3 (10 mL), NH4OH (5 mL) and NaHCO3 (5 mL), and stirred for 30 min. The layers were separated and the aqueous layer was extracted with CHCl3 (2×20 mL). The combined organic extracts were washed with NaHCO3, water and brine, dried over MgSO4, filtered and concentrated. The product was purified by preparative HPLC (gradient of 20-90% aqueous methanol with 1% TFA) and the HCl salt formed to afford Example 300 as a light yellow solid (4 mg, 3%). MS (M+H)+ =462+
