反应详情

温度

25 °C

In a round bottom flask was placed 1-(2-methoxy-ethyl)-1H-pyrazol-3-ylamine (prepared in Example 72, 51 mg, 0.36 mmol), 2,6-lutidine (57 μL, 0.49 mmol) and methylene chloride (5 mL) which was then cooled to 0° C. in an ice bath. To this solution was then added dropwise a solution of 3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-propionyl chloride in methylene chloride (prepared as in Example 102, ˜0.16 M solution, 2 mL, 0.33 mmol). The reaction was then allowed to warm up to 25° C. and stirred for 16 h. After this time the reaction mixture was diluted with methylene chloride (5 mL) transferred to a separatory funnel and washed with a saturated aqueous sodium bicarbonate solution (10 mL) and then a 1 N aqueous hydrochloric acid solution (10 mL) and then dried over magnesium sulfate, filtered and concentrated in vacuo. Purification on an AnaLogix Intelliflash system (4 g column, 25% ethyl acetate/hexanes to 45% ethyl acetate/hexanes) afforded (R)-3-cyclopentyl-2-(3,4-dichloro-phenyl)-N-[1-(2-methoxy-ethyl)-1H-pyrazol-3-yl]-propionamide (85 mg, 63%) as a white foam: [α]30589=−24.0° (c=0.10, methylene chloride); ES-HRMS m/e calcd for C20H25N3O2Cl2 (M+H)+ 410.1397, observed 410.1396; 1H NMR (300 MHz, DMSO-d6) δ 1.09 (m, 2H, CH2), 1.38-1.79 (m, 8H, 4×CH2), 2.05 (m, 1H, CH), 3.19 (s, 3H, OCH3), 3.61 (t, J=5.4 Hz, 2H, OCH2), 3.79 (m, 1H, ArCHCO), 4.12 (t, J=5.4 Hz, 2H, NCH2), 6.41 (d, J=2.2 Hz, 1H, Ar), 7.34 (dd, Jm=2.1 Hz, Jo=8.4 Hz, 1H, Ar), 7.54 (d, J=2.2 Hz, 1H, Ar), 7.59 (d, Jo=8.4 Hz, 1H, Ar), 7.59 (d, Jm=2.1 Hz, 1H, Ar), 10.72 (s, 1H, NH).

1. customIn a round bottom flask was placed
2. customtransferred to a separatory funnel
3. washwashed with a saturated aqueous sodium bicarbonate solution (10 mL)
4. dry with materiala 1 N aqueous hydrochloric acid solution (10 mL) and then dried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customPurification on an AnaLogix Intelliflash system (4 g column, 25% ethyl acetate/hexanes to 45% ethyl acetate/hexanes)