Hydrochloric Acid → HCID 67373292, compound

HRID 401999Notes

Reaction equation

HRID 401999 reaction equation
[ClH:1].Cl.[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:31][CH:32]2[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]2)=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[C:17]([NH:19][S:20]([CH3:23])(=[O:22])=[O:21])[CH:18]=1)[CH2:4][CH2:5][CH3:6].[CH2:39](Br)[CH:40]([CH3:42])[CH3:41].C(=O)([O-])[O-].[K+].[K+].Cl>CN(C=O)C.O.CCOC(C)=O.C(Cl)Cl.CCOCC>[ClH:1].[ClH:1].[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:31][CH:32]2[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]2)=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[C:17]([N:19]([CH2:39][CH:40]([CH3:42])[CH3:41])[S:20]([CH3:23])(=[O:21])=[O:22])[CH:18]=1)[CH2:4][CH2:5][CH3:6]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 65551-Bromo-2-methylpropaneHCID 11430Potassium CarbonateHCID 67374404HCID 67374404, compound

Product 1

HCID 67373292HCID 67373292, compoundYield 117.7%

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of N-{5-[3-butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-2-cyclohexyloxy-phenyl}-methanesulfonamide dihydrochloride (0.1 mmol, 59 mg) in DMF (1.0 mL) was added isobutyl bromide (0.2 mmol, 22 μL), and potassium carbonate (0.4 mmol, 56 mg). And the mixture was stirred at 90° C. for 2 hours. It was then diluted with water/EtOAc. 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, condensed, triturated with hexanes to provide the title compound (38 mg). LCMS: m/z 574 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.39 (1H, d), 7.31 (1H, s), 7.25 (1H, d), 7.04 (1H, s), 5.42 (1H, bs), 4.46-4.53 (1H, m), 3.42-3.48 (1H, m), 2.98-3.30 (5H, m), 2.95 (3H, s), 2.90-2.94 (2H, m), 2.69 (3H, s), 2.09-2.30 (6H, m), 1.82-1.88 (2H, m), 1.20-1.69 (11H, m), 0.89-0.93 (6H, m), 0.79 (3H, t).

Workup

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

Sources & evidence

ORD record
ord-1da9906e8c0746568fab71a814f97056
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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