1,4-Dioxane → 2-(1-(6-Fluoro-3-(pyridin-2-yl)quinoxalin-2-yl)ethyl)isoindoline-1,3-dione

HRID 75387

반응식

HRID 75387 반응식
Cl[C:2]1[C:3]([CH:13]([N:15]2[C:23](=[O:24])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]2=[O:25])[CH3:14])=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8]([F:12])=[CH:7][CH:6]=2.C([Sn](CCCC)(CCCC)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=1)CCC.O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(Cl)Cl>[F:12][C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[N:4]=[C:3]([CH:13]([N:15]1[C:23](=[O:24])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]1=[O:25])[CH3:14])[C:2]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=1)=[N:11]2

참가 물질

6

반응물 3

HCID 312751,4-DioxaneHCID 6077842-(Tributylstannyl)pyridineHCID 866985212-(1-(3-Chloro-6-fluoroquinoxalin-2-yl)ethyl)isoindoline-1,3-dione

생성물 1

HCID 668313902-(1-(6-Fluoro-3-(pyridin-2-yl)quinoxalin-2-yl)ethyl)isoindoline-1,3-dione수율 94.1%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  1. concentrationconcentrated under reduced pressure
  2. customto give a green syrupy solid
  3. temperatureThe mixture was heated
  4. temperatureunder reflux for 20 min
  5. temperaturecooled to 0° C.
  6. filtrationThe solid was collected by filtration
  7. washwashed with EtOAc-hexane (1:5, 500 mL)

출처 및 근거

ORD 기록
ord-8b1425409d904403936893ce7937fd41
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835432B2

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