反应详情

(S)—N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide (2.57 mmol, 692 mg) was dissolved in DCM (10 mL), thionyl chloride (5.14 mmol, 0.373 mL, 611 mg) added and the solution stirred at room temperature. After 45 min the mixture was concentrated then azeotroped with dichloromethane (4×10 mL) to give a yellow oil. To this oil was added dimethylformamide (10 mL) and potassium carbonate (7.71 mmol, 1.07 g) followed by ethyl 3-(trifluoromethyl)-1H-pyrazole-4-carboxylate (2.57 mmol, 0.54 g). The mixture was heated to 70° C. with stirring for 1 h. The reaction was concentrated to remove DMF before partitioning between EtOAc/water. The phases were mixed and separated and the aqueous phase further washed with EtOAc (×2). Combined organics were dried and concentrated to give a light yellow oil which was purified on silica eluting with 30% EtOAc/heptane. Desired fractions were collected and concentrated to give (S)-ethyl-1-((2-(1-methylethylsulfonamido)-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate as a colourless solid (0.65 g, 55.1%). 1H NMR (400 MHz, CDCl3) δ 1.33 (t, 3H) 1.39 (d, 6H) 2.9 (m, 2H) 3.17 (sept, 1H) 3.30 (m, 2H) 4.30 (m, 4H) 5.29 (s, 2H) 7.12 (m, 2H) 7.24 (d, 1H) 7.89 (s, 1H)

1. concentrationAfter 45 min the mixture was concentrated
2. customthen azeotroped with dichloromethane (4×10 mL)
3. customto give a yellow oil
4. temperatureThe mixture was heated to 70° C.
5. stirringwith stirring for 1 h
6. concentrationThe reaction was concentrated
7. customto remove DMF
8. custombefore partitioning between EtOAc/water
9. additionThe phases were mixed
10. customseparated
11. washthe aqueous phase further washed with EtOAc (×2)
12. customCombined organics were dried
13. concentrationconcentrated
14. customto give a light yellow oil which
15. customwas purified on silica eluting with 30% EtOAc/heptane
16. customDesired fractions were collected
17. concentrationconcentrated