Hydrochloric Acid → HCID 67372562, compound

HRID 2168758Notes

Reaction equation

HRID 2168758 reaction equation
[ClH:1].Cl.[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:28][CH:29]2[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]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)=[C:15]([O:26]C)[CH:14]=1)[CH2:4][CH2:5][CH3:6].C[S-].[Na+].O.Cl>CN(C=O)C.C(Cl)Cl.CCOCC>[ClH:1].[ClH:1].[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:28][CH:29]2[CH2:34][CH2:33][N:32]([CH3:35])[CH2:31][CH2:30]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)=[C:15]([OH:26])[CH:14]=1)[CH2:4][CH2:5][CH3:6]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 4378561Sodium methanethiolateHCID 67374691HCID 67374691, compound

Product 1

HCID 67372562HCID 67372562, compoundYield 142.4%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 3-butyl-4-(4-cyclohexyloxy-3-methoxy-phenyl)-6-(1-methyl-piperidin-4-yloxy)-pyridazine dihydrochloride (Example 73, 0.2 mmol, 104 mg) in dry DMF (2.0 mL), sodium thiomethoxide (1.0 mmol, 70 mg) was added and the resulting mixture was stirred at 100° C. for 2 hours. At completion, it was poured into water and extracted with ethyl acetate. 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 (1.0 mL), 2N HCl in ether (1.0 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (73 mg). LCMS: m/z 441 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.10 (1H, d), 6.98-7.03 (2H, m), 6.90-6.93 (1H, m), 5.46 (1H, bs), 4.31-4.38 (1H, m), 3.11-3.37 (4H, m), 2.91-2.96 (2H, m), 2.79 (3H, s), 2.11-2.36 (4H, m), 1.97-2.03 (2H, m), 1.80-1.86 (2H, m), 1.32-1.63 (8H, m), 1.20-1.29 (2H, m), 0.80 (3H, t).

Workup

  1. extractionextracted with ethyl acetate
  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-4d3e44a968fb43f48261f2de3db3c913
Source dataset
uspto-grants-2015_06
Patent number
US09045461B2

Reaction notes

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