Lithium Hydroxide → HCID 178440228, compound

HRID 1620280Notes

Reaction equation

HRID 1620280 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.Cl.Cl[CH2:21][C:22]1[C:23]([NH:34][CH2:35][CH2:36][O:37][CH3:38])=[N:24][C:25]2[C:30]([CH:31]=1)=[CH:29][C:28]([O:32][CH3:33])=[CH:27][CH:26]=2.[Li+].[OH-]>C1COCC1>[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[CH2:21][C:22]1[C:23]([NH:34][CH2:35][CH2:36][O:37][CH3:38])=[N:24][C:25]2[C:30]([CH:31]=1)=[CH:29][C:28]([O:32][CH3:33])=[CH:27][CH:26]=2

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 681822733-(chloromethyl)-6-methoxy-N-(2-methoxyethyl)quinolin-2-amine hydrochlorideHCID 178440211HCID 178440211, compound

Product 1

HCID 178440228HCID 178440228, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6,7-dimethoxy-1-propylisoquinolin-3-ol RBO 35134 (312 mg, 1.3 mmol) in THF (13 mL) in a 20 mL microwave vial equipped with a magnetic stirrer were added 3-(chloromethyl)-6-methoxy-N-(2-methoxyethyl)quinolin-2-amine hydrochloride SLA 47064B (400 mg, 1.3 mmol) and a 2 N aq. LiOH solution (1.26 mL, 2.52 mmol) and the mixture was stirred at 160° C. for 1.5 h under microwave irradiation. After cooling to room temperature, THF was removed at 40° C. under vacuum and the residue was then taken up in CH2Cl2 (50 mL), washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated under vacuum. Purification by column chromatography (SiO2, eluent CH3CN:H2O:TFA=100:0:0.05 to 50:50:0.05) gave 6,7-dimethoxy-4-((6-methoxy-2-(2-methoxyethylamino)quinolin-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 0.149 M HCl solution in MeOH (2.0 mL). The reaction mixture was stirred for 5 min at room temperature and concentrated at 40° C. under vacuum to afford 6,7-dimethoxy-4-((6-methoxy-2-(2-methoxyethylamino)quinolin-3-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 76 as a brown solid (39.5 mg, 5% yield).

Workup

  1. customTHF was removed at 40° C. under vacuum
  2. washwashed with brine (10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customPurification by column chromatography (SiO2, eluent CH3CN:H2O:TFA=100:0:0.05 to 50:50:0.05)

Sources & evidence

ORD record
ord-ff468ce5d6ed464cbe9c866194e891ce
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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