Potassium Hydroxide → HCID 178437782, compound

HRID 1620149Notes

Reaction equation

HRID 1620149 reaction equation
[CH2:1]([C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=2)[CH:6]=[C:5]([OH:17])[N:4]=1)[CH3:2].[OH-].[K+].Cl[CH2:21][C:22]1[CH:34]=[CH:33][C:25]2[O:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[C:24]=2[CH:23]=1>C1(C)C=CC=CC=1.C(Cl)Cl>[CH:23]1[C:24]2[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[O:26][C:25]=2[CH:33]=[CH:34][C:22]=1[CH2:21][C:6]1[C:7]2[C:12](=[CH:11][C:10]([O:13][CH3:14])=[C:9]([O:15][CH3:16])[CH:8]=2)[C:3]([CH2:1][CH3:2])=[N:4][C:5]=1[OH:17]

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 2337372-(Chloromethyl)dibenzofuranHCID 178437769HCID 178437769, compound2×

Product 1

HCID 178437782HCID 178437782, compoundYield 11%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 1-ethyl-6,7-dimethoxyisoquinolin-3-ol SLA 28136 (50 mg, 214 μmol) in toluene (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added a 2 N aq. KOH solution (0.11 mL, 0.22 mmol) at RT followed by 2-(chloromethyl)dibenzo[b,d]furan CCH 34116-2 (47 mg, 217 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 a mixture CH2Cl2:MeOH=9:1 (50 mL), washed with brine (10 mL), dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 96:4) gave 4-(dibenzo[b,d]furan-2-ylmethyl)-1-ethyl-6,7-dimethoxyisoquinolin-3-ol (10 mg, 11%). 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 0.2 M HCl solution in MeOH (0.25 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to afford 4-(dibenzo[b,d]furan-2-ylmethyl)-1-ethyl-6,7-dimethoxyisoquinolin-3-ol hydrochloride 6 as a pale brown solid (11 mg, 11% yield).

Workup

  1. temperatureAfter cooling to RT
  2. washMeOH=9:1 (50 mL), washed with brine (10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated at 40° C. under vacuum
  6. customPurification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 96:4)

Sources & evidence

ORD record
ord-563c1f0b9a554c168205a7a77690dccf
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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