Lithium Hydroxide → HCID 178486611, compound

HRID 1620286Notes

Reaction equation

HRID 1620286 reaction equation
[CH:1]([C:4]1[C:13]2[C:8](=[CH:9][C:10]([O:16][CH3:17])=[C:11]([O:14][CH3:15])[CH:12]=2)[CH:7]=[C:6]([OH:18])[N:5]=1)([CH3:3])[CH3:2].Cl.Cl[CH2:21][C:22]1[CH:23]=[N:24][C:25]2[C:30]([CH:31]=1)=[CH:29][CH:28]=[CH:27][CH:26]=2.Cl.ClCC1C(NCCOC)=NC2C(C=1)=CC(OC)=CC=2.[Li+].[OH-]>C1COCC1>[CH:1]([C:4]1[C:13]2[C:8](=[CH:9][C:10]([O:16][CH3:17])=[C:11]([O:14][CH3:15])[CH:12]=2)[C:7]([CH2:21][C:22]2[CH:23]=[N:24][C:25]3[C:30]([CH:31]=2)=[CH:29][CH:28]=[CH:27][CH:26]=3)=[C:6]([OH:18])[N:5]=1)([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 3939Lithium HydroxideHCID 145481263-(Chloromethyl)quinoline hydrochlorideHCID 681822733-(chloromethyl)-6-methoxy-N-(2-methoxyethyl)quinolin-2-amine hydrochlorideHCID 178486705HCID 178486705, compound2×

Product 1

HCID 178486611HCID 178486611, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-isopropyl-6,7-dimethoxyisoquinolin-3-ol SIL 32164 (462 mg, 1.87 mmol) in THF (13 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added a 3-(chloromethyl)quinoline hydrochloride SLA 47064B (400 mg, 1.87 mmol) and a 2 N aq. LiOH solution (1.87 mL, 3.74 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 CH2Cl2:MeOH=100:0 to 94:6) provided 1-isopropyl-6,7-dimethoxy-4-(quinolin-3-ylmethyl)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 0.149 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 1-isopropyl-6,7-dimethoxy-4-(quinolin-3-ylmethyl)isoquinolin-3-ol dihydrochloride 79 as a yellow solid (76 mg, 9% 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 CH2Cl2:MeOH=100:0 to 94:6)

Sources & evidence

ORD record
ord-0428c531871c4da9b31a3537fd031a6c
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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