2-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-YL)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-C]pyridin-4-one → 2-(3-(tert-butylamino)-2-((2,4-dimethoxybenzyl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

HRID 1056162Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1056162
[C:1]([NH:5][C:6]1[C:7]([NH:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][C:28]=2[O:35][CH3:36])=[N:8][C:9]2[C:14]([N:15]=1)=[C:13](B1OC(C)(C)C(C)(C)O1)[CH:12]=[CH:11][CH:10]=2)([CH3:4])([CH3:3])[CH3:2].CC1(C)C(C)(C)OB([C:45]2[NH:53][C:52]3[CH2:51][CH2:50][NH:49][C:48](=[O:54])[C:47]=3[CH:46]=2)O1>O1CCOCC1.O.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].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[C:1]([NH:5][C:6]1[C:7]([NH:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][C:28]=2[O:35][CH3:36])=[N:8][C:9]2[C:14]([N:15]=1)=[C:13]([C:45]1[NH:53][C:52]3[CH2:51][CH2:50][NH:49][C:48](=[O:54])[C:47]=3[CH:46]=1)[CH:12]=[CH:11][CH:10]=2)([CH3:4])([CH3:3])[CH3:2]

Komponenten

8

Edukt 2

HCID 897834962-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-YL)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-C]pyridin-4-oneHCID 89793840N3-(tert-butyl)-N2-(2,4-dimethoxybenzyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoxaline-2,3-diamine

Produkt 1

HCID 897938422-(3-(tert-butylamino)-2-((2,4-dimethoxybenzyl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-oneAusbeute 125 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator2×HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylKatalysator2×HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
105 °C

Versuchsvorschrift

A mixture of N3-(tert-butyl)-N2-(2,4-dimethoxybenzyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoxaline-2,3-diamine (304c; 109.6 mg, 0.09 mmol), 2-bromo-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (608) (80 mg, 0.37 mmol), K2PO4 (59 mg, 0.28 mmol), X-Phos (Strem Chemicals, Inc.) (4.46 mg, 9.35 μmol), and Pd2dba3 (Aldrich) (4.28 mg, 4.67 μmol) in a mixture of dioxane (1.0 mL) and water (0.20 mL) was stirred under argon at 105° C. for 3 h. Additional Pd2dba3 (4.28 mg, 4.67 μmol) and dicyclohexyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (4.46 mg, 9.35 μmol) were added, and the resulting mixture was stirred under argon at 105° C. for 15 h. The reaction mixture was subsequently diluted with DCM (10 mL) and concentrated onto silica gel. Chromatographic purification (silica gel, 0-100% EtOAc/hexanes, then 0-10% MeOH/DCM) furnished 2-(3-(tert-butylamino)-2-((2,4-dimethoxybenzyl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (56.3 mg) as a yellow solid: m/z (ESI, +ve) 501.2 (M+H)+.

Aufarbeitung

  1. stirringthe resulting mixture was stirred under argon at 105° C. for 15 h
  2. concentrationconcentrated onto silica gel
  3. customChromatographic purification (silica gel, 0-100% EtOAc/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-2e9b9008c1fc4c77bae854a0f6d882e3
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09394297B2

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