反应详情

To a solution of 1-(diisopropoxymethyl)-1H-benzo[d]imidazole (318 mg, 1.280 mmol) in THF (5 mL) at 0° C. is added LiHMDS (0.753 mL, 0.753 mmol) over 1 min. The reaction was stirred 5 min., then 3.5 mL of the 6 mL solution (1.0 theoretical equivalent of the lithium benzoimidazole) was added to a solution of tert-butyl 3-(2-(4-(ethoxycarbonyl)phenoxy)pyridin-3-yl)azetidine-1-carboxylate (300 mg, 0.753 mmol) in THF (3 mL) at 0° C. The reaction was stirred at 0° C. 30 min. LCMS showed only 5% conversion. The remaining solution of benzoimidazole was added and the reaction stirred 1 h at 0° C. LCMS shows 2:1 ratio of starting material to desired product. The reaction was quenched with 2 N HCl (15 mL) and warmed to rt and stirred overnight. The aqueous layer was neutralized with solid Na2CO3 and the aqueous layer extracted with CH2Cl2 (2×25 mL). The combined organic fractions were washed with saturated NaCl, dried (MgSO4), and concentrated. The crude material was then taken up in MeOH (3 mL) and 4.0 M HCl in dioxane was added. The reaction was stirred at rt 2 h, then concentrated to give the crude amine hydrochloride, which was taken on to the next step without purification.

1. stirringThe reaction was stirred at 0° C
2. custom30 min
3. stirringthe reaction stirred 1 h at 0° C