反応 #47240

反応方程式

(S)-3-cyclohexyl-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionic acid

1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol

benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate

triethylamine

→

(S)-3-cyclohexyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionamide

収率 51.0%

溶媒

dichloromethane

dichloromethane

反応条件

後処理

1. 1
   洗浄washed with 2N aqueous hydrochloric acid, saturated sodium bicarbonate solution, saturated sodium chloride solution
2. 2
   その他dried
3. 3
   濃縮The organic layer was concentrated
4. 4
   その他the crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 80 g; 0% to 10% methanol/dichloromethane)

実験手順

A solution of (S)-3-cyclohexyl-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionic acid (1.3 g, 4.87 mmol) in dichloromethane (25 mL) was treated with 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 830 mg, 5.36 mmol), benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (2.60 g, 5.84 mmol) and triethylamine (1.48 g, 14.61 mmol). The reaction mixture was stirred for 18 h at 25° C., under nitrogen. The reaction mixture was diluted with dichloromethane, washed with 2N aqueous hydrochloric acid, saturated sodium bicarbonate solution, saturated sodium chloride solution and dried. The organic layer was concentrated, and the crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 80 g; 0% to 10% methanol/dichloromethane) to afford (S)-3-cyclohexyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionamide (1.0 g, 51%) as a heavy yellow oil: LR-ES-MS m/z calculated for C21H32N4O4 [M]+ 404, observed [M+H]+ 405.

出典