Potassium Hydroxide → HCID 178440237, compound

HRID 1620186Notes

Reaction equation

HRID 1620186 reaction equation
C(C1C2C(=CC(OC)=C(OC)C=2)C=C(O)N=1)C.[CH3:18][O:19][C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][C:29]=1[O:30][CH3:31])[C:26]([CH2:32][CH2:33][CH3:34])=[N:25][C:24]([OH:35])=[CH:23]2.[OH-].[K+].Cl.Cl[CH2:40][C:41]1[CH:42]=[N:43][C:44]2[C:49]([CH:50]=1)=[CH:48][CH:47]=[C:46]([O:51][CH3:52])[CH:45]=2>C1(C)C=CC=CC=1.C(Cl)Cl.O>[CH3:18][O:19][C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][C:29]=1[O:30][CH3:31])[C:26]([CH2:32][CH2:33][CH3:34])=[N:25][C:24]([OH:35])=[C:23]2[CH2:40][C:41]1[CH:42]=[N:43][C:44]2[C:49]([CH:50]=1)=[CH:48][CH:47]=[C:46]([O:51][CH3:52])[CH:45]=2

Participants

8

Reactant 4

HCID 14797Potassium HydroxideHCID 681822023-(Chloromethyl)-7-methoxyquinoline hydrochloride2×HCID 178437769HCID 178437769, compoundHCID 178440211HCID 178440211, compound

Product 1

HCID 178440237HCID 178440237, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 1-ethyl-6,7-dimethoxyisoquinolin-3-ol RBO 35142 (117 mg, 473 μmol) in toluene (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added a 2 N aq. KOH solution (0.52 mL, 1.04 mmol) at RT followed by 3-(chloromethyl)-7-methoxyquinoline hydrochloride MDE 32012 (124 mg, 508 μmol) and the mixture was stirred at 150° C. for 2 h under microwave irradiation. After cooling to RT, the mixture was diluted with CH2Cl2 (50 mL) and H2O (10 mL). The organic phase was isolated and the aqueous phase was further extracted with CH2Cl2 (50 mL). The combined organic phase was 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 95:5) gave 26 mg of 6,7-dimethoxy-4-((7-methoxyquinolin-3-yl)methyl)-1-propylisoquinolin-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 (2.0 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to afford 6,7-dimethoxy-4-((7-methoxyquinolin-3-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 32 as a brown solid (30 mg, 13% 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. washThe combined organic phase was 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 95:5)

Sources & evidence

ORD record
ord-25387bd80e734af1b72f1a3534b940e0
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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