反应详情

Methyl 3-{[methyl(propyl)amino]carbonyl}-5-(1,3-thiazol-2-yl)benzoate (390 mg, 1.22 mmol) is dissolved in 1:1:1 tetrahydrofuran/methanol/water (9 mL), and lithium hydroxide monohydrate is added (103 mg, 2.4 mmol), and the reaction stirred 2 h. The solution is concentrated under reduced pressure. The residue is redissolved in DMF (5 mL), and diisopropylethylamine (355 μL, 2.0 mmol), HATU (230 mg, 0.61 mmol), (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol dihydrochloride prepared by the method of EXAMPLE SP-272 (206 mg, 0.51 mmol) are added. The reaction stirred at room temperature 16 h. The reaction mixture is diluted with ethyl acetate, washed with water, saturated sodium bicarbonate, saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 9% methanol/methylene chloride) provides the title compound. ESI MS m/z 621.3 [M+H]+.

1. additionis added (103 mg, 2.4 mmol)
2. concentrationThe solution is concentrated under reduced pressure
3. dissolutionThe residue is redissolved in DMF (5 mL)
4. additionare added
5. stirringThe reaction stirred at room temperature 16 h
6. washwashed with water, saturated sodium bicarbonate, saturated sodium chloride
7. dry with materialdried (sodium sulfate)
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customPurification by flash column chromatography (silica, 9% methanol/methylene chloride)