反应详情

温度

45 °C

To a solution of (R)—N,N-dimethyl-2-(2-neopentyl-5-(pyrrolidin-3-ylsulfonyl)-1H-benzo[d]imidazol-1-yl)ethanamine (STEP C, 453 mg, 1.15 mmol) in 1,4-dioxane (5 mL) was added 37% formalin (343 microL, 4.27 mmol) and formic acid (221 microL, 5.77 mmol) at 0° C. The mixture was stirred at 45° C. for 1 h. The mixture was concentrated in vacuo. The residue was diluted with sodium bicarbonate aqueous solution and extracted with ethyl acetate (60 mL×2). The combined organic layers were washed with brine and dried over sodium sulfate. The resulting solution was concentrated and residue was purified by amine gel column chromatography (dichloromethane-ethyl acetate, gradient) to give the title compound (419 mg, 89%) as a clear grease.

1. concentrationThe mixture was concentrated in vacuo
2. additionThe residue was diluted with sodium bicarbonate aqueous solution
3. extractionextracted with ethyl acetate (60 mL×2)
4. washThe combined organic layers were washed with brine
5. dry with materialdried over sodium sulfate
6. concentrationThe resulting solution was concentrated
7. customresidue was purified by amine gel column chromatography (dichloromethane-ethyl acetate, gradient)