Potassium Phosphate, Tribasic → 2-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

HRID 1056140노트

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HRID 1056140 반응식
Br[C:2]1[C:3]([F:18])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:12][C:13]([CH3:16])([CH3:15])[CH3:14])[C:8]([CH3:17])=[N:7]2.CC1(C)C(C)(C)OB([C:27]2[NH:35][C:34]3[CH2:33][CH2:32][NH:31][C:30](=[O:36])[C:29]=3[CH:28]=2)O1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[C:13]([NH:12][C:9]1[C:8]([CH3:17])=[N:7][C:6]2[C:11]([N:10]=1)=[C:2]([C:27]1[NH:35][C:34]3[CH2:33][CH2:32][NH:31][C:30](=[O:36])[C:29]=3[CH:28]=1)[C:3]([F:18])=[CH:4][CH:5]=2)([CH3:16])([CH3:15])[CH3:14]

참가 물질

9

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 897819348-bromo-N-(tert-butyl)-7-fluoro-3-methylquinoxalin-2-amineHCID 897834962-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-YL)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-C]pyridin-4-one

생성물 1

HCID 717315152-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one수율 39.1%

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매

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온도
110 °C

실험 절차

A glass microwave reaction vessel (80 mL) was charged with 8-bromo-N-(tert-butyl)-7-fluoro-3-methylquinoxalin-2-amine (286a) (1.20 g, 3.84 mmol) and 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (609; 1.81 g, 6.92 mmol) in 1,4-dioxane (15 mL)/water (4.8 mL). Then Pd2(dba)3 (Strem Chemicals,) (0.176 g, 0.19 mmol), Xphos (Strem Chemicals,) (181 mg, 0.38 mmol) and potassium phosphate tribasic (Fisher Scientific, Fair Lawn, N.J.) (2.45 g, 11.53 mmol) were added into the reaction mixture. The glass vessel was sealed and heated in a CEM Voyager Microwave (Matthews, N.C.; large-scale unit) at 110° C. for 20 min (50 watts, Powermax feature off). The mixture was diluted with DCM (50 mL) and filtered through AW Standard Super-Celt NF (Sigma-Aldrich). The filtrate was concentrated in-vacuo and the crude residue was diluted with DCM, then filtered through a fine-fritted funnel. The crude material was purified by chromatography through an Interchim PuriFlash UP pre-packed silica-gel column (Interchim INC, San Pedro, Calif.; 200 gram), eluted with a gradient of 0-8% EtOAc in CH2Cl2 (for recovery of the starting material, 8-bromo-N-(tert-butyl)-7-fluoro-3-methylquinoxalin-2-amine), then with a gradient of 0-5% MeOH in DCM, to provide 2-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (286) (0.55 g, 1.50 mmol, 39% yield) as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.09 (br., 1H), 7.65 (dd, J=9.00, 5.87 Hz, 1H), 7.26-7.34 (m, 1H), 6.95-7.01 (m, 1H), 6.73-6.77 (m, 1H), 6.15 (s, 1H), 3.41-3.48 (m, 2H), 2.86 (t, J,=,6.85 Hz, 2H), 2.55 (s, 3H), 1.51 (s, 9H). m/z (ESI, +ve) 368 (M+H).

후처리

  1. customA glass microwave reaction vessel (80 mL)
  2. customThe glass vessel was sealed
  3. filtrationfiltered through AW Standard Super-Celt NF (Sigma-Aldrich)
  4. concentrationThe filtrate was concentrated in-vacuo
  5. additionthe crude residue was diluted with DCM
  6. filtrationfiltered through a fine-fritted funnel
  7. customThe crude material was purified by chromatography through an Interchim PuriFlash UP pre-packed silica-gel column (Interchim INC, San Pedro, Calif.; 200 gram)
  8. washeluted with a gradient of 0-8% EtOAc in CH2Cl2 (for recovery of the starting material, 8-bromo-N-(tert-butyl)-7-fluoro-3-methylquinoxalin-2-amine), then with a gradient of 0-5% MeOH in DCM

출처 및 근거

ORD 기록
ord-cf2bb7aab78d4e36bc145a24bd48356e
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394297B2

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