Dimethylformamide → N-(1-azabicyclo[3.3.1]non-5-ylmethyl)-1H-indole-3-carboxamide

참여 물질

반응 단계

A solution of 1-methyl-1H-indole-3-carboxylic acid (1.53 g, 8.7 mmol) in anhydrous tetrahydrofuran (8 mL) under nitrogen was treated with 1.49 g (9.2 mmol) of 1,1'-carbonyldiimidazole (CDI) and stirred for 10 minutes. At this point a thick suspension formed, and anhydrous N,N-dimethylformamide (8 mL) was added. After an additional 45 minutes the solution was degassed under a stream of nitrogen over 10 minutes, then treated with a solution of 1-azabicyclo[3.3.1]nonane-5-methanamine (1.47 g, 9.5 mmol). After 18 hours at room temperature and six hours at 55°-60° C., no acid-CDI adduct was detected by TLC (5% methanol/methylene chloride on alumina), and the mixture was concentrated in vacuo. The residue was partitioned between 3N sodium hydroxide (50 mL) and toluene (100 mL) containing a little 2-propanol. The organic layer as separated and the aqueous solution was extracted with toluene (50 mL) containing some 2 -propanol. The combined organic solution was dried (Na2SO4), concentrated in vacuo, and the residue filtered through alumina (eluted with 20% methanol/tetrahydrofuran). The filtrate was concentrated in vacuo and the residue triturated from ether/petroleum ethers (30°-60° ) to give a solid, which was recrystallized from tetrahydrofuran/hexane to afford 2.06 g (76%) of colorless crystals; mp 145°-147° C.

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