Potassium Hydroxide → HCID 178486662, compound

HRID 1620169Notes

Reaction equation

HRID 1620169 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]=[C:24]2[C:29](=[CH:30][CH:31]=1)[N:28]=[CH:27][CH:26]=[CH:25]2.N1C2C(=CC(CO)=CC=2)C=CC=1>COCCOC.O=S(Cl)Cl>[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])=[C:6]2[CH2:21][C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][CH:31]=1)[N:28]=[CH:27][CH:26]=[CH:25]2

Participants

7

Reactant 4

HCID 14797Potassium HydroxideHCID 15143856-HydroxymethylquinolineHCID 200819696-(Chloromethyl)quinoline hydrochlorideHCID 178486704HCID 178486704, compound2×

Product 1

HCID 178486662HCID 178486662, compound

Reagents, catalysts & solvents 2

HCID 80711,2-DimethoxyethaneSolventHCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
115 °C

Procedure

To a solution of 6,7-dimethoxy-1-methylisoquinolin-3-ol CCH 18060 (200 mg, 0.912 mmol) in DME (5 mL) in a 10 mL microwave vial equipped with a magnetic stirrer was added a 2 N aq. KOH solution (0.95 mL, 1.90 mmol) at RT followed by 6-(chloromethyl)quinoline hydrochloride (234 mg, 1.093 mmol, prepared by stirring quinolin-6-yl methanol (330 mg) in SOCl2 (1 mL) for 1 h at RT, then concentration under vacuum and repeated coevaporation with CH2Cl2 and the mixture was stirred at 115° C. for 25 min under microwave irradiation. After cooling to RT, the mixture was diluted with H2O (5 mL) before extraction with EtOAc (50 mL). The organic phase was washed with brine (10 mL) and the aqueous phase was further extracted with CH2Cl2 (50 mL). The dichloromethane phase was washed with brine (10 mL), combined with the first organic phase, dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 92:8) gave 37 mg of 6,7-dimethoxy-1-methyl-4-(quinolin-6-ylmethyl)isoquinolin-3-ol as a yellow solid. This free base was dissolved in MeOH (10 mL) in a 25 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.09 M HCl solution in MeOH (4.0 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to afford 6,7-dimethoxy-1-methyl-4-(quinolin-6-ylmethyl)isoquinolin-3-ol dihydrochloride 24 as a brown solid (44 mg, 11% yield).

Workup

  1. customprepared
  2. concentrationconcentration under vacuum
  3. temperatureAfter cooling to RT
  4. additionthe mixture was diluted with H2O (5 mL) before extraction with EtOAc (50 mL)
  5. washThe organic phase was washed with brine (10 mL)
  6. extractionthe aqueous phase was further extracted with CH2Cl2 (50 mL)
  7. washThe dichloromethane phase was washed with brine (10 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated at 40° C. under vacuum
  11. customPurification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 92:8)

Sources & evidence

ORD record
ord-b07c134bd27a4b9b86c7738f8b39a062
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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