Dichloromethane → 4-[1-(3-Hydroxypropyl)-1H-pyrazol-4-yl]-2-methyl-7-nitro-2,3-dihydro-1H-isoindol-1-one

Participants

Reaction Steps

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 1I, 1.825 g, 5.736 mmol), 3-(4-bromo-1H-pyrazol-1-yl)propan-1-ol (1.45 g, 7.07 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (510 mg, 0.62 mmol), and potassium carbonate (2.4 g, 17.3 mmol) in dioxane (20 mL) and H2O (5 mL) was irradiated in a microwave reactor for 45 min at 100° C. The reaction mixture was poured into water and extracted with CH2Cl2 three times. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, concentrated in vacuo, and purified using a Teledyne ISCO CombiFlash® Rf system (eluting with 0-15% MeOH:CH2Cl2) to isolate the desired compound as 920 mg as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 8.35 (s, 1H), 8.05 (s, 1H), 7.99 (d, J=8.3 Hz, 1H), 7.88 (d, J=8.3 Hz, 1H), 4.72 (s, 2H), 4.63 (t, J=5.1 Hz, 1H), 4.25 (t, J=7.1 Hz, 2H), 3.43 (q, J=6.1 Hz, 2H), 3.11 (s, 3H), 1.98 (quin, J=6.6 Hz, 2H). HRMS (ESI): m/z 317.11 [M+H]+. UPLC: tR=0.91 min (UPLC-TOF: polar—3 min).

Provenance & Evidence