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

HRID 2168695Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2168695
[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 (2 H, m), 7.38-7.41 (2 H, m), 7.32-7.35 (2 H, m), 7.12-7.15 (2 H, m), 7.02 (1 H, s), 5.47-5.53 (1 H, m), 5.16 (2 H, s), 3.30-3.49 (4 H, m), 2.91 (3 H, s), 2.89-2.94 (2 H, m), 2.22-2.37 (4 H, m), 1.44-1.52 (2 H, m), 1.18-1.26 (2 H, m), 0.79 (3 H, 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-ab1c4426bf63487b92b2d2a1c1093a16
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09045461B2

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