反应详情

(S)-4-(2-(2-bromoacetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)ethyl)-3,5-dichloropyridine (mixture obtained as described in Example 5, Step 1, 100 mg, 0.18 mmol) is dissolved in DMF (2 ml), then K2CO3 (30 mg, 0.22 mmol) and 2,3-dihydro-3,3-dimethyl-1,2-benzisothiazole 1,1-dioxide (71 mg, 0.36 mmol) are added. The mixture is stirred at RT for 5 hours. The reaction is quenched with water (10 ml), and the product extracted with Ethyl Acetate. The organic layer is washed with H2O (3×15 ml), dried over Na2SO4 and evaporated under vacuum. The crude is purified by preparative HPLC (Method 2), to yield 100 mg of the title compound (85% yield). MS/ESI+ 657.51 [MH]+; 1H NMR (400 MHz, acetone) ppm 8.40 (s, 2H), 7.38 (m, 2H), 7.36 (m, 3H), 7.03 (m, 1H), 6.81 (m, 2H), 5.63 (m, 1H), 4.14 (s, 2H), 3.90 (d, 2H), 3.54-3.29 (2H), 3.25-3.00 (2m, 2H), 1.27 (s, 6H), 0.72 (m, 1H), 0.30-0.05 (2 m, 4H).

1. customThe reaction is quenched with water (10 ml)
2. extractionthe product extracted with Ethyl Acetate
3. washThe organic layer is washed with H2O (3×15 ml)
4. dry with materialdried over Na2SO4
5. customevaporated under vacuum
6. customThe crude is purified by preparative HPLC (Method 2)