反应详情

A solution of PdCl2(dppf)-CH2Cl2 adduct (0.017 g, 0.021 mmol), 4-(4-bromo-2-cyanophenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.124 g, 0.208 mmol), (2-fluorophenyl)boronic acid (0.032 g, 0.228 mmol, Aldrich) and potassium phosphate (0.220 g, 1.038 mmol) in dioxane (0.553 ml)/water (0.277 ml) was heated to 90° C. for 1 h until completion. The reaction was cooled to RT and then diluted with DCM and washed with water. The organics were dried via phase separator (Radleys Discovery Technologies) and concentrated in vacuo. The material was taken up in a mixture of DCM and methanol, and further purified using a 2-g SCX column (product eluted with methanol wash). After concentration, DCM (1.0 mL) and TFA (0.5 mL) were added and stirred at RT for 3 h until complete deprotection. The reaction was concentrated in vacuo and purified via silica-gel chromatography, eluting with 0-100% ethyl acetate in heptanes to yield, after concentration, 4-(3-cyano-2′-fluoro-[1,1′-biphenyl]-4-yl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.082 g, 0.166 mmol, 80% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.79-3.86 (m, 2 H) 4.32-4.40 (m, 2 H) 6.64 (d, J=8.51 Hz, 1 H) 6.80 (d, J=4.50 Hz, 1 H) 7.17-7.21 (m, 1 H) 7.21-7.24 (m, 2 H) 7.31-7.40 (m, 2 H) 7.45-7.53 (m, 1 H) 7.60-7.68 (m, 2 H) 7.95 (dt, J=8.56, 1.83 Hz, 1 H) 8.11 (s, 1 H) 12.62 (br. S., 1 H). m/z (ESI) 493.0 (M+H)+.

1. washwashed with water
2. customThe organics were dried via phase separator (Radleys Discovery Technologies)
3. concentrationconcentrated in vacuo
4. additionThe material was taken up in a mixture of DCM and methanol
5. customfurther purified
6. washa 2-g SCX column (product eluted with methanol wash)
7. concentrationAfter concentration, DCM (1.0 mL) and TFA (0.5 mL)
8. additionwere added
9. concentrationThe reaction was concentrated in vacuo
10. custompurified via silica-gel chromatography
11. washeluting with 0-100% ethyl acetate in heptanes
12. customto yield