反应详情

温度

-78 °C

Ethyl 3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-2-fluorobenzoate (37-1) (240 mg, 0.54 mmol, 1.0 eq) was dissolved in THF (4 mL). The reaction mixture was cooled to −78° C. and methylmagnesium bromide (0.91 mL, 2.7 mmol, 3.0 M, 5.0 eq) was added. The resulting mixture stirred at ambient temperature for 30 minutes. The reaction was quenched by the addition of NH4Cl (2 mL), extracted with EtOAc (50 mL), washed with water (10 mL) and brine (10 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by flash chromatography (40 g SiO2, 10-70% EtOAc in hexanes) to afford 2-(3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-2-fluorophenyl)propan-2-ol (37-2) as a yellow solid. 1H NMR (400 MHz, CDCl3): δ 7.81 (td, J=1.6, 7.6 Hz, 1 H); 7.59 (td, J=1.6, 7.6 Hz, 1 H); 7.42 (dd, J=2.0, 8.0 Hz, 1 H); 7.23 (t, J=7.6 Hz, 1 H); 7.06 (d, J=8.0 Hz, 1 H); 3.81-4.03 (m, 2 H); 3.49 (s, 3 H); 2.15 (m, 1 H); 1.69 (s, 6 H); 1.66 (m, 1 H); 1.39 (m, 1 H). HRMS m/z (M+H) 428.1242 found, 428.1250 required.

1. customThe reaction was quenched by the addition of NH4Cl (2 mL)
2. extractionextracted with EtOAc (50 mL)
3. washwashed with water (10 mL) and brine (10 mL)
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe crude residue was purified by flash chromatography (40 g SiO2, 10-70% EtOAc in hexanes)