Potassium Phosphate, Tribasic → 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-1H-pyrrolo[2,3-d]pyridazin-4(5H)-one

HRID 1056303Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1056303
Br[C:2]1[NH:11][C:5]2[CH:6]=[N:7][NH:8][C:9](=[O:10])[C:4]=2[CH:3]=1.[C:12]([NH:16][C:17]1[C:26]([CH3:27])=[N:25][C:24]2[C:19](=[C:20](B3OC(C)(C)C(C)(C)O3)[CH:21]=[CH:22][CH:23]=2)[N:18]=1)([CH3:15])([CH3:14])[CH3:13].[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.O.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].CO.C(Cl)Cl>[C:12]([NH:16][C:17]1[C:26]([CH3:27])=[N:25][C:24]2[C:19]([N:18]=1)=[C:20]([C:2]1[NH:11][C:5]3[CH:6]=[N:7][NH:8][C:9](=[O:10])[C:4]=3[CH:3]=1)[CH:21]=[CH:22][CH:23]=2)([CH3:15])([CH3:14])[CH3:13]

Komponenten

9

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 89783758N-(tert-butyl)-3-methyl-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoxalin-2-amineHCID 1365086292-bromo-1H-pyrrolo[2,3-d]pyridazin-4(5H)-one

Produkt 1

HCID 1365086282-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-1H-pyrrolo[2,3-d]pyridazin-4(5H)-oneAusbeute 22 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittelHCID 21226129Dichloromethane methanolLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A mixture of 2-bromo-1H-pyrrolo[2,3-d]pyridazin-4(5H)-one (47.0 mg, 0.220 mmol), N-(tert-butyl)-3-methyl-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoxalin-2-amine (174b; 94 mg, 0.220 mmol), K3PO4 (140 mg, 0.659 mmol), Pd2dba3 (Aldrich; 10.05 mg, 10.98 μmol), and XPhos (Strem Chemicals, Inc., 10.47 mg, 0.022 mmol) in a mixture of dioxane (1.5 mL) and water (0.38 mL) was stirred under argon at 70° C. for 1.5 h. The reaction mixture was subsequently heated at 90° C. for 17 h. The reaction mixture was then concentrated onto silica gel and chromatographically purified (silica gel, 50-100% EtOAc/hexanes, then 0-10% MeOH/DCM) to provide 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-1H-pyrrolo[2,3-d]pyridazin-4(5H)-one (16.8 mg, 0.048 mmol, 22% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.60 (1H, br. s.), 12.24 (1H, s), 8.16 (1H, d, J=0.4 Hz), 7.97 (1H, dd, J=7.4, 1.4 Hz), 7.75 (1H, dd, J=8.0, 1.4 Hz), 7.43 (1H, t, J=7.7 Hz), 7.38 (1H, s), 6.11 (1H, s), 2.58 (3H, s), 1.54 (9H, s). m/z (ESI, +ve) 349.0 (M+H)+.

Aufarbeitung

  1. temperatureThe reaction mixture was subsequently heated at 90° C. for 17 h
  2. concentrationThe reaction mixture was then concentrated onto silica gel
  3. customchromatographically purified (silica gel, 50-100% EtOAc/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-0b4613d4d0a647e58577a8b81c6e62f0
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09394297B2

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