Cesium carbonate → N-[2-(2,6-Dichlorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-yl]-pyridazine-3,6-diamine

HRID 626668Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 626668
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[CH:18]=[C:12]2[C:13]([NH2:17])=[N:14][CH:15]=[CH:16][C:11]2=[N:10]1.[NH2:19][C:20]1[N:21]=[N:22][C:23](Cl)=[CH:24][CH:25]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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]>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[CH:18]=[C:12]2[C:13]([NH:17][C:23]3[N:22]=[N:21][C:20]([NH2:19])=[CH:25][CH:24]=3)=[N:14][CH:15]=[CH:16][C:11]2=[N:10]1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 216436-Amino-3-chloropyridazineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 696711782-(2,6-Dichlorophenyl)-2h-pyrazolo[4,3-c]pyridin-4-amine

Produkt 1

HCID 69671267N-[2-(2,6-Dichlorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-yl]-pyridazine-3,6-diamineAusbeute 13 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

A mixture of 2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine-4-ylamine (100 mg, 0.36 mmol), 3-amino-6-chloropyridazine (57 mg, 0.44 mmol), Pd2(dba)3 (8 mg, 0.009 mmol), Xantphos (21 mg, 0.036 mmol) and cesium carbonate (234 mg, 0.72 mmol) in dioxane (2.5 mL) was degassed with argon then heated at 150° C. for 30 minutes in a microwave reactor. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (4-7% methanol in DCM) to afford the title compound as a beige solid (17 mg, 13% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.45 (d, J=0.9 Hz, 1H), 7.95-7.89 (m, 2H), 7.86-7.84 (m, 2H), 7.76 (dd, J=9.1, 7.2 Hz, 1H), 7.62 (d, J=9.7 Hz, 1H), 7.57-7.53 (m, 1H). LCMS (Method B): RT=2.56 min, m/z: 372 [M+H+].

Aufarbeitung

  1. customwas degassed with argon
  2. customThe reaction mixture was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel flash chromatography (4-7% methanol in DCM)

Quellen und Nachweise

ORD-Eintrag
ord-4ffbbf21ed944cf2b1333169b1326a5b
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09309240B2

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