تفاعل #162569

ord-8b1425409d904403936893ce7937fd41

المذيبات

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    تركيزconcentrated under reduced pressure
  2. 2
    أخرىto give a green syrupy solid
  3. 3
    درجة الحرارةThe mixture was heated
  4. 4
    درجة الحرارةunder reflux for 20 min
  5. 5
    درجة الحرارةcooled to 0° C.
  6. 6
    ترشيحThe solid was collected by filtration
  7. 7
    غسيلwashed with EtOAc-hexane (1:5, 500 mL)

الإجراء التجريبي

A solution of 2-(1-(3-chloro-6-fluoroquinoxalin-2-yl)ethyl)isoindoline-1,3-dione (50.14 g, 140.9 mmol), 2-tri-n-butylstannylpyridine (80% pure) (76.95 ml, 211.4 mmol), and tetrakis(triphenylphosphine)palladium(0) (16.29 g, 14.09 mmol) in 1,4-dioxane (1175 ml, 140.9 mmol) was stirred at 110° C. for 29 h. After 29 h, the mixture was cooled to rt and concentrated under reduced pressure to give a green syrupy solid. To the residue was added DCM (200 mL). The mixture was heated under reflux for 20 min and then cooled to 0° C. with stirring. The solid was collected by filtration and washed with EtOAc-hexane (1:5, 500 mL) to give the desired product (52.82 g, 94.07% yield). The dark brown solid was dissolved in CH2Cl2:MeOH (9:1, 400 mL, warm), filtered through a plug of silica gel (150 g, 8.5 cm diameter×5.5 cm height) to remove residual palladium and washed with CH2Cl2:MeOH (9:1, 600 mL). The filtrate was concentrated under reduced pressure to give a brown solid (49.94 g, 88.9% yield). The brown solid was suspended in EtOAc-hexane (1:9, 400 mL) and the mixture was heated under reflux for 40 min. The mixture was cooled to rt, filtered, washed with EtOAc-hexane (1:9, 600 mL), and dried to give the desired product 2-(1-(6-fluoro-3-(pyridin-2-yl)quinoxalin-2-yl)ethyl)isoindoline-1,3-dione (47.76 g, 85.06% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.47-8.53 (m, 1H), 8.20 (dd, J=9.4, 5.9 Hz, 1H), 7.94 (dd, J=9.4, 2.7 Hz, 1H), 7.85 (td, J=8.9, 2.9 Hz, 1H), 7.64-7.80 (m, 6H), 7.30-7.37 (m, 1H), 6.42 (q, J=6.9 Hz, 1H), 1.76 (d, J=7.0 Hz, 3H). Mass Spectrum (ESI) m/e=399.1 (M+1).

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08835432B2uspto-grants-2014_09