Potassium Hydroxide → HCID 178466130, compound

HRID 1620180Notes

Reaction equation

HRID 1620180 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)=[C:29]([O:32][CH2:33][CH3:34])[CH:28]=[CH:27][CH:26]=2>C1(C)C=CC=CC=1.O.CCOC(C)=O>[CH2:33]([O:32][C:29]1[CH:28]=[CH:27][CH:26]=[C:25]2[C:30]=1[CH:31]=[C:22]([CH2:21][C:6]1[C:5]3[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=3)[C:9]([CH3:15])=[N:8][C:7]=1[OH:16])[CH:23]=[N:24]2)[CH3:34]

Participants

7

Reactant 3

HCID 14797Potassium HydroxideHCID 68182410HCID 68182410, compoundHCID 178486704HCID 178486704, compound2×

Product 1

HCID 178466130HCID 178466130, 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 (51 mg, 233 μmol) in toluene (15 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added a 2 N aq. KOH solution (0.22 mL, 0.44 mmol) at RT followed by CCH 29192 (50 mg, 194 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 layer was isolated and the aqueous layer was further extracted with CH2Cl2 (50 mL). Both organic layers 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 4-((5-ethoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-methylisoquinolin-3-ol. This free base was dissolved in MeOH (2 mL) in a 10 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.09 M HCl solution in MeOH (2 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to afford 4-((5-ethoxyquinolin-3-yl)methyl)-6,7-dimethoxy-1-methylisoquinolin-3-ol dihydrochloride 28 as a yellow solid (11 mg, 12% yield).

Workup

  1. temperatureAfter cooling to RT
  2. customThe organic layer was isolated
  3. extractionthe aqueous layer was further extracted with CH2Cl2 (50 mL)
  4. washBoth organic layers 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-287dbf73dbf24b588c293b99893d92ad
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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