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 1056140Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1056140
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]

Komponenten

9

Edukt 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

Produkt 1

HCID 717315152-(3-(tert-butylamino)-6-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-oneAusbeute 39,1 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-cf2bb7aab78d4e36bc145a24bd48356e
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09394297B2

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