Potassium Hydroxide → HCID 178482302, compound

HRID 1620250Notes

Reaction equation

HRID 1620250 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[C:23]([NH:35][CH3:36])=[N:24][C:25]2[CH:26]=[C:27]3[O:34][CH2:33][O:32][C:28]3=[CH:29][C:30]=2[CH:31]=1>C1(C)C=CC=CC=1.C(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[C:23]([NH:35][CH3:36])=[N:24][C:25]2[CH:26]=[C:27]3[O:34][CH2:33][O:32][C:28]3=[CH:29][C:30]=2[CH:31]=1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 68182129HCID 68182129, compound2×HCID 178486704HCID 178486704, compound2×

Product 1

HCID 178482302HCID 178482302, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 6,7-dimethoxy-1-methylisoquinolin-3-ol CCH 18060 (147 mg, 670 μmol) in toluene (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added a 2 N aq. KOH solution (0.70 mL, 1.40 mmol) at RT followed by 7-(chloromethyl)-N-methyl-[1,3]dioxolo[4,5-g]quinolin-6-amine hydrochloride CCH 34158B (200 mg, 697 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 CH2Cl2:MeOH=9:1 (80 mL) and the organic solution was washed with brine (10 mL), dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:7 N NH3 solution in MeOH=100:0 to 95:5) gave 6,7-dimethoxy-1-methyl-4-((6-(methylamino)-[1,3]dioxolo[4,5-g]quinolin-7-yl)methyl)isoquinolin-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 0.19 M HCl solution in MeOH (1 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-((6-(methylamino)-[1,3]dioxolo[4,5-g]quinolin-7-yl)methyl)isoquinolin-3-ol dihydrochloride 60 as a brown solid (30 mg, 6% yield).

Workup

  1. temperatureAfter cooling to RT
  2. washMeOH=9:1 (80 mL) and the organic solution was 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 CH2Cl2:7 N NH3 solution in MeOH=100:0 to 95:5)

Sources & evidence

ORD record
ord-d0c65497343f4e089a565baba09bef63
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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