Hydrochloric Acid → HCID 67371415, compound

HRID 2168634Notes

Reaction equation

HRID 2168634 reaction equation
[ClH:1].Cl.[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:26][CH:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)=[CH:11][C:12]=1[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)=[CH:15][CH:14]=1)[CH2:4][CH2:5][CH3:6].[CH3:33][O:34][CH2:35][CH2:36]Br.C(=O)([O-])[O-].[K+].[K+].Cl>CCO.C(Cl)Cl.CCOCC>[ClH:1].[ClH:1].[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:26][CH:27]2[CH2:32][CH2:31][N:30]([CH2:36][CH2:35][O:34][CH3:33])[CH2:29][CH2:28]2)=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)=[CH:17][CH:18]=1)[CH2:4][CH2:5][CH3:6]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 809722-Bromoethyl methyl etherHCID 67375293HCID 67375293, compound

Product 1

HCID 67371415HCID 67371415, compoundYield 96.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 3-butyl-4-(4-cyclohexyloxy-phenyl)-6-(piperidin-4-yloxy)-pyridazine dihydrochloride (Example 14, 0.2 mmol, 97 mg) in EtOH (2 mL) was added 2-bromoethyl methyl ether (0.6 mmol, 57 μL), and potassium carbonate (0.6 mmol, 83 mg). The mixture was stirred at 60° C. for 3 hours, then cooled to room temperature, and filtered through celite. The celite cake was washed with DCM. The organic layers were combined and condensed in vacuo, and the residue was purified by silica gel chromatography (DCM to DCM+10% 2N NH3 in MeOH) to give a colorless sticky solid, which was dissolved in DCM (2 mL), 1N HCl in ether (2 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (52 mg). LCMS: m/z 469 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.31-7.40 (3 H, m), 7.06-7.10 (2 H, m), 5.38-5.57 (1 H, m), 4.39-4.44 (1 H, m), 3.53-3.78 (4 H, m), 3.43 (3 H, s), 3.25-3.42 (4 H, m), 2.96-3.02 (2 H, m), 2.04-2.55 (4 H, m), 1.97-2.02 (2 H, m), 1.78-1.83 (2 H, m), 1.29-1.62 (8 H, m), 1.22-1.30 (2 H, m), 0.80 (3 H, t).

Workup

  1. temperaturecooled to room temperature
  2. filtrationfiltered through celite
  3. washThe celite cake was washed with DCM
  4. customcondensed in vacuo
  5. customthe residue was purified by silica gel chromatography (DCM to DCM+10% 2N NH3 in MeOH)
  6. customto give a colorless sticky solid, which
  7. waitkept at room temperature for 10 min
  8. customcondensed
  9. customtriturated with hexanes

Sources & evidence

ORD record
ord-8bfcdaae250b46d2b5721b856a054073
Source dataset
uspto-grants-2015_06
Patent number
US09045461B2

Reaction notes

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