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

HRID 401967Notes

Reaction equation

HRID 401967 reaction equation
[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]

Participants

9

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
80 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-1c5c98faa69c45089a4fc08344684559
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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