反应详情

To a solution of 2-cyclopropyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid (synthesized according to the methods described in sections a) to d) of example X1) (0.15 g, 0.57 mmol) in dichloromethane (10 ml) are added N-ethyl-diisopropylamine (0.24 ml, 1.43 mmol), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (0.13 g, 0.69 mmol), and 1-hydroxybenzotriazole hydrate (0.015 g, 0.11 mmol). The mixture is stirred for 15 min at RT, and then cooled to 0° C., before (1R,2S)-2-(aminomethyl)cyclohexanol (0.07 g, 0.57 mmol) is added and stirring is continued for 3 days. After completion of the reaction, the mixture is diluted with ethyl acetate and 10% aqueous ammonium chloride. The organic layer is separated and washed with saturated sodium hydrogencarbonate solution and brine, dried over magnesium sulphate and evaporated to dryness. The crude product is purified by flash chromatography (silica gel, 30% ethyl acetate/cyclohexane) to yield 2-cyclopropyl-N-[[(1S,2R)-2-hydroxy-cyclohexyl]-methyl]-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide (example X2) (0.21 g, 0.56 mmol, 98%). [M+H]+374.2.

1. additionis added
2. stirringstirring
3. waitis continued for 3 days
4. customAfter completion of the reaction
5. customThe organic layer is separated
6. washwashed with saturated sodium hydrogencarbonate solution and brine
7. dry with materialdried over magnesium sulphate
8. customevaporated to dryness
9. customThe crude product is purified by flash chromatography (silica gel, 30% ethyl acetate/cyclohexane)