Hydrochloric Acid → HCID 67387599, compound

HRID 1972033Notes

Reaction equation

HRID 1972033 reaction equation
[ClH:1].Cl.[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[C:21]([O:23][CH:24]3[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]3)[N:20]=[N:19][C:18]=2[CH2:30][CH2:31][CH2:32][CH3:33])=[CH:13][C:12]=1[O:34][CH3:35])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C=O.O.[C:39](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>ClCCl.C(O)(=O)C.O.CCOC(C)=O.C([O-])(O)=O.[Na+].CCOCC>[ClH:1].[ClH:1].[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[C:21]([O:23][CH:24]3[CH2:29][CH2:28][N:27]([CH3:39])[CH2:26][CH2:25]3)[N:20]=[N:19][C:18]=2[CH2:30][CH2:31][CH2:32][CH3:33])=[CH:13][C:12]=1[O:34][CH3:35])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 962WaterHCID 5049666Sodium triacetoxyborohydrideHCID 67374614HCID 67374614, compound

Product 1

HCID 67387599HCID 67387599, compoundYield 166.1%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolventHCID 22728543Water ethylacetateSolvent

Procedure

To a solution of 4-(4-benzyloxy-3-methoxy-phenyl)-3-butyl-6-(piperidin-4-yloxy)-pyridazine dihydrochloride (1.0 mmol, 520 mg) in dichloromethane (5.0 mL) was added formaldehyde solution in water (37%, 10 mmol, 1.0 mL), and 2 drops of acetic acid. Then sodium triacetoxyborohydride (4.0 mmol, 848 mg) was added. And the mixture was stirred at room temperature for 0.5 hour then condensed. It was then diluted with water/EtOAc and neutralized with NaHCO3 powder. The solvent was removed 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 (5.0 mL), 2N HCl in ether (5.0 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to afford 4-(4-benzyloxy-3-methoxy-phenyl)-3-butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazine dihydrochloride (444 mg).

Workup

  1. customcondensed
  2. customThe solvent was removed in vacuo
  3. customthe residue was purified by silica gel chromatography (DCM to DCM+10% 2N NH3 in MeOH)
  4. customto give a colorless sticky solid, which
  5. waitkept at room temperature for 10 min
  6. customcondensed
  7. customtriturated with hexanes

Sources & evidence

ORD record
ord-9ff5bac92bc4497fa27bbdcbd47d30c8
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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