Lithium Hydroxide → HCID 178440234, compound

HRID 1620287Notes

Reaction equation

HRID 1620287 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[CH:23]=[C:24]2[C:29](=[CH:30][CH:31]=1)[N:28]=[C:27]([CH3:32])[CH:26]=[CH:25]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[CH:23]=[C:24]2[C:29](=[CH:30][CH:31]=1)[N:28]=[C:27]([CH3:32])[CH:26]=[CH:25]2

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 68182032HCID 68182032, compoundHCID 178440211HCID 178440211, compound

Product 1

HCID 178440234HCID 178440234, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6,7-dimethoxy-1-propylisoquinolin-3-ol RBO 35134 (434 mg, 1.75 mmol) in THF (13 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added a 6-(chloromethyl)-2-methylquinolinehydrochloride SLA 47080B (400 mg, 1.75 mmol) and a 2 N aq. LiOH solution (1.75 mL, 3.50 mmol) and the mixture was stirred at 160° C. for 1.5 h under microwave irradiation. After cooling to RT, THF was removed at 40° C. under vacuum and the residue was 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 EtOAc:MeOH=100:0 to 95:5) followed by a new purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 95:5) provided 6,7-dimethoxy-4-((2-methylquinolin-6-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 0.49 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-((2-methylquinolin-6-yl)methyl)-1-propylisoquinolin-3-ol dihydrochloride 80 as a yellow solid (28 mg, 3% 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 EtOAc:MeOH=100:0 to 95:5)
  7. customfollowed by a new purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 95:5)

Sources & evidence

ORD record
ord-ee530ff161c24a36a304eebda1da2d10
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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