Lithium Hydroxide → HCID 178440215, compound

HRID 1620252Notes

Reaction equation

HRID 1620252 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]([CH2:15][CH2:16][CH3:17])=[N:8][C:7]([OH:18])=[CH:6]2.[Li+].[OH-].[ClH:21].[Cl:22][CH2:23][C:24]1[C:25]([NH:37][CH3:38])=[N:26][C:27]2[CH:28]=[C:29]3[O:36][CH2:35][O:34][C:30]3=[CH:31][C:32]=2[CH:33]=1>C1(C)C=CC=CC=1.C(Cl)Cl>[ClH:22].[ClH:21].[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]([CH2:15][CH2:16][CH3:17])=[N:8][C:7]([OH:18])=[C:6]2[CH2:23][C:24]1[C:25]([NH:37][CH3:38])=[N:26][C:27]2[CH:28]=[C:29]3[O:36][CH2:35][O:34][C:30]3=[CH:31][C:32]=2[CH:33]=1

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 68182129HCID 68182129, compound2×HCID 178440211HCID 178440211, compound2×

Product 1

HCID 178440215HCID 178440215, compoundYield 9%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 6,7-dimethoxy-1-propylisoquinolin-3-ol RBO 35142 (245 mg, 0.99 mmol) in toluene (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added a 2 N aq. LiOH solution (1.00 mL, 2.00 mmol) at RT followed by 7-(chloromethyl)-N-methyl-[1,3]dioxolo[4,5-g]quinolin-6-amine hydrochloride CCH 34158B (284 mg, 0.99 mmol) 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, after evaporation, 6,7-dimethoxy-4-((6-(methylamino)-[1,3]dioxolo[4,5-g]quinolin-7-yl)methyl)-1-propylisoquinolin-3-ol. This free base was dissolved in MeOH (3 mL) in a 10 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.19 M HCl solution in MeOH (2 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to afford 6,7-dimethoxy-4-((6-(methylamino)-[1,3]dioxolo[4,5-g]quinolin-7-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 62 as a beige solid (46 mg, 9% 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)
  7. customgave
  8. customafter evaporation, 6,7-dimethoxy-4-((6-(methylamino)-[1,3]dioxolo[4,5-g]quinolin-7-yl)methyl)-1-propylisoquinolin-3-ol
  9. dissolutionThis free base was dissolved in MeOH (3 mL) in a 10 mL round-bottomed flask
  10. customequipped with a magnetic stirrer before addition of a 0.19 M HCl solution in MeOH (2 mL)
  11. stirringThe reaction mixture was stirred for 5 min at RT
  12. concentrationconcentrated at 40° C. under vacuum

Sources & evidence

ORD record
ord-083535d1691a4a8facbfb3ab2fc2030a
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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