Hydrochloric Acid → HCID 67373076, compound

HRID 401905Notes

Reaction equation

HRID 401905 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].[Cl:33][CH2:34][C:35]([CH3:38])([OH:37])[CH3:36].C(=O)([O-])[O-].[K+].[K+].Cl>CCO.O.CCOC(C)=O.C(Cl)Cl.CCOCC>[ClH:33].[ClH:1].[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:26][CH:27]2[CH2:32][CH2:31][N:30]([CH2:34][C:35]([CH3:38])([OH:37])[CH3:36])[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

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 684091-Chloro-2-methylpropan-2-olHCID 67375293HCID 67375293, compound

Product 1

HCID 67373076HCID 67373076, compoundYield 77.5%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
50 °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 1-chloro-2-methyl-2-propanol (0.4 mmol, 44 μL), and potassium carbonate (0.6 mmol, 83 mg). And the mixture was stirred at 50° C. for 4 hours. 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 (2 mL), 1N HCl in ether (2 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to yield 1-{4-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxy]-piperidin-1-yl}-2-methyl-propan-2-ol dihydrochloride (86 mg, 77% yield). LCMS: m/z 483 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.53 and 7.62 (1H, s), 7.41-7.46 (2H, m), 7.10-7.14 (2H, m), 5.42-5.52 (1H, m), 4.41-4.46 (1H, m), 3.65-3.83 (2H, m), 3.25-3.47 (3H, m), 3.05-3.12 (2H, m), 2.22-2.55 (5H, m), 1.98-2.03 (2H, m), 1.78-1.83 (2H, m), 1.40-1.63 (7H, m), 1.38 (6H, s), 1.22-1.36 (3H, m), 0.81 (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. waitkept at room temperature for 10 min
  6. customcondensed
  7. customtriturated with hexanes

Sources & evidence

ORD record
ord-5573803b13494bc1b97707e3a2f94c8d
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

Loading…