反应详情

A mixture of compound 58 (0.155 g, 0.58 mmoles) and methyl 2-(aminomethyl)pyridine-4-carboxylate dihydrochloride (0.139 g, 0.58 mmoles) (see WO2003070732, example 6, step 2 for preparation, which is incorporated by reference in its entirety) in dichloromethane (20 ml) was treated with N,N,N′,N′-tetramethyl-O-(1H-benzotriazol-1-yl)uranium hexafluorophosphate (0.264 g, 0.69 mmoles) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.133 g, 0.69 mmoles) and N-methylmorpholine (0.255 ml, 2.32 mmoles) then stirred at ambient temperature under a nitrogen atmosphere for 18 h. The mixture was washed with water (2×20 ml) and saturated brine (20 ml) then separated and dried over sodium sulphate, filtered and evaporated to dryness. The residue was chromatographed on silica gel eluting with an ethyl acetate/isohexane gradient. This gave the title compound as a colorless oil (0.184 g 76%).

1. washThe mixture was washed with water (2×20 ml) and saturated brine (20 ml)
2. customthen separated
3. dry with materialdried over sodium sulphate
4. filtrationfiltered
5. customevaporated to dryness
6. customThe residue was chromatographed on silica gel eluting with an ethyl acetate/isohexane gradient