反应详情

A suspension of 2-methyl-7-nitro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-isoindol-1-one (Compound 289C, 1.825 g, 5.736 mmol), 3-(4-bromo-1H-pyrazol-1-yl)propan-1-ol (1.449 g, 7.066 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (509.5 mg, 0.6239 mmol), and potassium carbonate (2.397 g, 17.34 mmol) in a 4:1 ratio of dioxane (20 mL) to H2O (5 mL) was evacuated and charged with nitrogen several times. The sample was irradiated under microwave conditions [Biotage, 100° C.] for 45 min. The reaction mixture was transferred to a separatory funnel, brine was added, and the reaction was extracted with CH2Cl2. The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude was adsorbed onto a pre-filled solid loading cartridge [RediSepRf 25 gram] and purified using the Teledyne/ISCO system [RediSepRf 40 gram silica GOLD], slowly eluting with 0-15% MeOH:CH2Cl2. Fractions containing product were pooled together and concentrated in vacuo, yielding the title material as a yellow solid, 920.0 mg (50%, 2.850 mmol). 1H NMR (400 MHz, DMSO-d6) δ 8.35 (s, 1H), 8.05 (s, 1H), 7.99 (d, J=8.34 Hz, 1H), 7.88 (d, J=8.34 Hz, 1H), 4.72 (s, 2H), 4.63 (t, J=5.05 Hz, 1H), 4.25 (t, J=7.07 Hz, 2H), 3.43 (q, J=6.06 Hz, 2H), 3.11 (s, 3H), 1.98 (quin, J=6.63 Hz, 2H). MS (ES+): m/z 317.11 (100) [MH+]. HPLC: tR=0.91 min (TOF, polar—3 min).

1. customwas evacuated
2. additioncharged with nitrogen several times
3. customThe sample was irradiated under microwave conditions [Biotage, 100° C.] for 45 min
4. customThe reaction mixture was transferred to a separatory funnel
5. additionbrine was added
6. extractionthe reaction was extracted with CH2Cl2
7. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. custompurified
11. washslowly eluting with 0-15% MeOH
12. additionFractions containing product
13. concentrationconcentrated in vacuo