Hydrochloric Acid → HCID 67375608, compound

HRID 401900Notes

Reaction equation

HRID 401900 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].Br[CH2:34][CH2:35][OH:36].C(=O)([O-])[O-].[K+].[K+].Cl>CCO.O.CCOC(C)=O.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]([CH2:34][CH2:35][OH: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 108982-BromoethanolHCID 11430Potassium CarbonateHCID 67375293HCID 67375293, compound

Product 1

HCID 67375608HCID 67375608, compoundYield 45.6%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 22728543Water ethylacetateSolvent

Procedure

To a solution of 3-butyl-4-(4-cyclohexyloxy-phenyl)-6-(piperidin-4-yloxy)-pyridazine dihydrochloride (Example 14, 0.1 mmol, 49 mg) in EtOH (1 mL) was added 2-bromoethanol (0.3 mmol, 22 μL), and potassium carbonate (0.4 mmol, 56 mg). The mixture was stirred at room temperature for 3 hours and 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% 2N ammonia in MeOH) to give a colorless sticky solid, which was dissolved in DCM (1 mL), 1N HCl in ether (1 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (12 mg). LCMS: m/z 456 [M+2]. 1H NMR (400 MHz, CD3OD): δ 7.78 (1H, s), 7.45-7.49 (2H, m), 7.12-7.17 (2H, m), 5.38-5.57 (1H, m), 4.41-4.48 (1H, m), 3.91-3.95 (2H, m), 3.60-3.81 (2H, m), 3.32-3.47 (4H, m), 3.12-3.17 (2H, m), 2.10-2.59 (5H, m), 1.98-2.04 (2H, m), 1.78-1.84 (2H, m), 1.35-1.63 (7H, m), 1.26-1.33 (2H, m), 0.82 (3H, t).

Workup

  1. customdried
  2. customcondensed in vacuo
  3. customthe residue was purified by silica gel chromatography (DCM to DCM+10% 2N ammonia 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-8ffd74c61923492f8c1f70652baf0e10
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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