Hydrochloric Acid → 3-Butyl-4-[4-(4-chloro-benzyloxy)-phenyl]-6-(1-methyl-piperidin-4-yloxy)-pyridazine dihydrochloride

HRID 401967Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 401967
[CH2:1]([C:5]1[N:6]=[N:7][C:8]([O:18][CH:19]2[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]2)=[CH:9][C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)[CH2:2][CH2:3][CH3:4].[Cl:26][C:27]1[CH:34]=[CH:33][C:30]([CH2:31]Br)=[CH:29][CH:28]=1.C(=O)([O-])[O-].[K+].[K+].[ClH:41]>CN(C=O)C.O.CCOC(C)=O.C(Cl)Cl.CCOCC>[ClH:26].[ClH:41].[CH2:1]([C:5]1[N:6]=[N:7][C:8]([O:18][CH:19]2[CH2:20][CH2:21][N:22]([CH3:25])[CH2:23][CH2:24]2)=[CH:9][C:10]=1[C:11]1[CH:12]=[CH:13][C:14]([O:17][CH2:31][C:30]2[CH:33]=[CH:34][C:27]([Cl:26])=[CH:28][CH:29]=2)=[CH:15][CH:16]=1)[CH2:2][CH2:3][CH3:4]

Komponenten

9

Edukt 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 1363862594-[3-Butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-phenol

Produkt 1

HCID 673751643-Butyl-4-[4-(4-chloro-benzyloxy)-phenyl]-6-(1-methyl-piperidin-4-yloxy)-pyridazine dihydrochloride

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 3283Diethyl EtherLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 22728543Water ethylacetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a solution of 4-[3-butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-phenol (Example 19, 0.2 mmol, 69 mg) in dry DMF (1 mL) was added 4-chlorobenzyl bromide (0.4 mmol, 83 mg), and potassium carbonate (0.4 mmol, 56 mg). And the mixture was stirred at 80° C. over night. It was then diluted with water/EtOAc. The organic layers were combined, dried, and condensed in vacuo and the residue was purified by silica gel chromatography (DCM to DCM+10% MeOH) to give a colorless sticky solid, which was dissolved in DCM (1.0 mL), 1N HCl in ether (1.0 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (69 mg). LCMS: m/z 467 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.44-7.47 (2H, m), 7.38-7.41 (2H, m), 7.32-7.35 (2H, m), 7.12-7.15 (2H, m), 7.02 (1H, s), 5.47-5.53 (1H, m), 5.16 (2H, s), 3.30-3.49 (4H, m), 2.91 (3H, s), 2.89-2.94 (2H, m), 2.22-2.37 (4H, m), 1.44-1.52 (2H, m), 1.18-1.26 (2H, m), 0.79 (3H, t).

Aufarbeitung

  1. customdried
  2. customcondensed in vacuo
  3. customthe residue was purified by silica gel chromatography (DCM to DCM+10% MeOH)
  4. customto give a colorless sticky solid, which
  5. customcondensed
  6. customtriturated with hexanes

Quellen und Nachweise

ORD-Eintrag
ord-1c5c98faa69c45089a4fc08344684559
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08741900B2

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