反应详情

温度

90 °C

A solution of (S)-methyl 2-(2-(3-bromophenyl)-7-iodo-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (0.160 g, 0.287 mmol) and 4-allyl-5-chloro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine (0.096 g, 0.287 mmol) in DMF (3 mL) was treated with 2.0 M aq. Na2CO3 (0.358 mL, 0.717 mmol), sparged with N2 for 10 min, treated with Pd(Ph3P)4 (0.033 g, 0.029 mmol), sparged for 5 min, then sealed and heated (90° C.) for 16 h. The reaction was cooled, diluted with EtOAc (20 mL) and washed with 1:1 water/brine (2×10 mL). The organic layer was dried (Na2SO4), filtered, and concentrated. The residue was purified by biotage column chromatography (4 g Isco SiO2, 0% (5 CV), 0%-80% (15 CV), EtOAc/hexanes) to afford semi-purified product (0.122 g, 0.143 mmol, 49.9% yield) as a clear oil. 1H NMR (500 MHz, CDCl3) δ 7.98 (t, J=1.7 Hz, 1H), 7.76 (dt, J=7.8, 1.2 Hz, 1H), 7.44 (ddd, J=8.0, 2.0, 1.1 Hz, 1H), 7.24 (t, J=7.9 Hz, 1H), 6.99-7.03 (m, 1H), 6.93-6.97 (m, 1H), 6.85 (s, 1H), 5.99-6.10 (m, 1H), 5.36 (dd, J=17.2, 1.6 Hz, 1H), 5.26 (dd, J=10.2, 1.5 Hz, 1H), 5.05 (s, 1H), 4.23-4.32 (m, 2H), 3.69 (dd, J=12.1, 6.0 Hz, 2H), 3.65 (s, 3H), 3.17-3.29 (m, 2H), 2.84 (s, 3H), 1.17 (s, 9H). LCMS (M+H)=641.2.

1. customsparged with N2 for 10 min
2. customsparged for 5 min
3. customsealed
4. temperatureThe reaction was cooled
5. additiondiluted with EtOAc (20 mL)
6. washwashed with 1:1 water/brine (2×10 mL)
7. dry with materialThe organic layer was dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified by biotage column chromatography (4 g Isco SiO2, 0% (5 CV), 0%-80% (15 CV), EtOAc/hexanes)