反应详情

温度

50 °C

A microwave vial was charged with 4-(2-bromo-4-(trifluoromethyl)phenyl)-N-(thiazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.076 g, 0.146 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2 H)-carboxylate (0.068 g, 0.219 mmol), Pd(AmPhos2)Cl2 (10.34 mg, 0.015 mmol), and potassium phosphate (0.093 g, 0.438 mmol). Dioxane (0.649 mL) and water (0.325 mL) were added, the vial was flushed with argon and sealed, and microwaved at 100° C. for 30 minutes. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was dissolved in DCM and TFA (0.1 mL, 1.298 mmol) was added. The reaction was stirred at 50° C. for one hour. The reaction was concentrated and the material was purified via silica gel column chromatography (12 g, gradient elution 0 to 10% MeOH:DCM) to afford 4-(2-(1,2,3,6-tetrahydropyridin-4-yl)-4-(trifluoromethyl)phenyl)-N-(thiazol-5-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide 2,2,2-trifluoroacetate (0.069 g, 0.108 mmol) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.71 (br. s., 1 H), 8.81 (br. s., 2 H), 8.70 (s, 1 H), 7.81-7.75 (m, 1 H), 7.63 (s, 1 H), 7.58 (d, J=8.2 Hz, 1 H), 7.35 (s, 1 H), 7.11 (d, J=2.2 Hz, 1 H), 7.06 (dd, J=2.1, 8.6 Hz, 1 H), 6.46 (d, J=8.6 Hz, 1 H), 5.86 (br. s., 1 H), 4.31 (d, J=4.1 Hz, 2 H), 3.66 (br. s., 2 H), 3.62 (t, J=4.1 Hz, 2 H), 3.17 (br. s., 3H), 2.42 (br. s., 1 H). m/z (ESI) 523.4 (M+H)+.

1. customthe vial was flushed with argon
2. customsealed
3. custommicrowaved at 100° C. for 30 minutes
4. additionThe reaction was diluted with ethyl acetate
5. washwashed with water
6. extractionThe aqueous layer was extracted with ethyl acetate
7. dry with materialthe combined organic layers were dried with sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. dissolutionThe material was dissolved in DCM
11. concentrationThe reaction was concentrated
12. customthe material was purified via silica gel column chromatography (12 g, gradient elution 0 to 10% MeOH:DCM)