Potassium Hydroxide → HCID 178465990, compound

HRID 1620184Notes

Reaction equation

HRID 1620184 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9]([CH3:15])=[N:8][C:7]([OH:16])=[CH:6]2.[OH-].[K+].Cl.Cl[CH2:21][C:22]1[CH:23]=[N:24][C:25]2[C:30]([CH:31]=1)=[CH:29][CH:28]=[C:27]([O:32][CH2:33][CH3:34])[CH:26]=2>C1(C)C=CC=CC=1.O.CCOC(C)=O>[CH2:33]([O:32][C:27]1[CH:26]=[C:25]2[C:30]([CH:31]=[C:22]([CH2:21][C:6]3[C:5]4[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=4)[C:9]([CH3:15])=[N:8][C:7]=3[OH:16])[CH:23]=[N:24]2)=[CH:29][CH:28]=1)[CH3:34]

Participants

7

Reactant 3

HCID 14797Potassium HydroxideHCID 68182194HCID 68182194, compoundHCID 178486704HCID 178486704, compound2×

Product 1

HCID 178465990HCID 178465990, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 6,7-dimethoxy-1-methylisoquinolin-3-ol CCH 18060 (112 mg, 511 μmol) in toluene (15 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added a 2 N aq. KOH solution (0.48 mL, 0.96 mmol) at RT followed by CCH 29190 (110 mg, 426 μmol) and the mixture was stirred at 150° C. for 1.5 h under microwave irradiation. After cooling to RT, the mixture was diluted with H2O (10 mL) before extraction with EtOAc (50 mL). The organic phase was isolated and the aqueous phase was further extracted with CH2Cl2 (50 mL). Both organic phases were washed with brine (10 mL), combined, dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 94:6) gave 47 mg of 4-((7-ethoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-methylisoquinolin-3-ol. The free base was dissolved in MeOH (2 mL) in a 10 mL round-bottomed flask equipped with a magnetic stirrer before addition of 0.09 M HCl in MeOH (4 mL) and the solution was stirred for 5 min at RT, and concentrated at 40° C. under vacuum to afford 4-((7-ethoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-methylisoquinolin-3-ol dihydrochloride 30 as a yellow solid (56 mg, 28% yield).

Workup

  1. temperatureAfter cooling to RT
  2. customThe organic phase was isolated
  3. extractionthe aqueous phase was further extracted with CH2Cl2 (50 mL)
  4. washBoth organic phases were washed with brine (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated at 40° C. under vacuum
  8. customPurification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 94:6)

Sources & evidence

ORD record
ord-3087696dc403480190c63990bf13767e
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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