Toluene → HCID 178486671, compound

HRID 1620172Notes

Reaction equation

HRID 1620172 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.ClC[C:22]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:25]=[CH:24][CH:23]=1.[C:32]1(C)C=CC=CC=1>O.CCOC(C)=O>[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[CH2:32][C:23]1[CH:24]=[N:25][C:26]2[C:31]([CH:22]=1)=[CH:30][CH:29]=[CH:28][CH:27]=2

Participants

7

Reactant 4

HCID 1140TolueneHCID 14797Potassium HydroxideHCID 230016194-(Chloromethyl)quinoline--hydrogen chloride (1/1)HCID 178486704HCID 178486704, compound2×

Product 1

HCID 178486671HCID 178486671, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
160 °C

Procedure

To a solution of 6,7-dimethoxy-1-methylisoquinolin-3-ol CCH 18060 (120 mg, 547 μmol) in toluene (15 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added a 2 N aq. KOH solution (0.58 mL, 1.16 mmol) at RT followed by MDE 32016 (130 mg, 607 μmol) and the mixture was stirred at 160° 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 92:8) gave 37 mg of 6,7-dimethoxy-1-methyl-4-(quinolin-3-ylmethyl)isoquinolin-3-ol. This free base was dissolved in MeOH (2 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 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-4-ylmethyl)isoquinolin-3-ol dihydrochloride 25 as a brown solid (44 mg, 19% 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 92:8)

Sources & evidence

ORD record
ord-b4d600584d1644c39cba486050cd24d8
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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