Lithium Hydroxide → HCID 178437779, compound

HRID 1620265Notes

Reaction equation

HRID 1620265 reaction equation
[CH2:1]([C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=2)[CH:6]=[C:5]([OH:17])[N:4]=1)[CH3:2].Cl.[N:19]([C:22]1[C:31]([CH2:32]Cl)=[CH:30][C:29]2[C:24](=[CH:25][CH:26]=[C:27]([O:34][CH3:35])[CH:28]=2)[N:23]=1)=[N+:20]=[N-:21].[Li+].[OH-]>C1COCC1>[N:19]([C:22]1[C:31]([CH2:32][C:6]2[C:7]3[C:12](=[CH:11][C:10]([O:13][CH3:14])=[C:9]([O:15][CH3:16])[CH:8]=3)[C:3]([CH2:1][CH3:2])=[N:4][C:5]=2[OH:17])=[CH:30][C:29]2[C:24](=[CH:25][CH:26]=[C:27]([O:34][CH3:35])[CH:28]=2)[N:23]=1)=[N+:20]=[N-:21]

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 86669829HCID 86669829, compound2×HCID 178437769HCID 178437769, compound2×

Product 1

HCID 178437779HCID 178437779, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
160 °C

Procedure

To a solution of 1-ethyl-6,7-dimethoxyisoquinolin-3-ol SLA 28136 (161 mg, 0.69 mmol) in THF (13 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added 2-azido-3-(chloromethyl)-6-methoxyquinoline hydrochloride SLA 41152 (197 mg, 0.69 mmol) followed by a 2 N aq. LiOH solution (0.69 mL, 1.38 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) gave 4-((2-azido-6-methoxyquinolin-3-yl)methyl)-1-ethyl-6,7-dimethoxyisoquinolin-3-ol (10 mg). 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 RT and concentrated at 40° C. under vacuum to afford 4-((2-azido-6-methoxyquinolin-3-yl)methyl)-1-ethyl-6,7-dimethoxyisoquinolin-3-ol dihydrochloride 68 as a yellow solid (11 mg, 3% yield).

Workup

  1. temperatureAfter cooling to RT
  2. customTHF was removed at 40° C. under vacuum
  3. washwashed with brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customPurification by column chromatography (SiO2, eluent EtOAc:MeOH=100:0 to 95:5)
  8. customfollowed by a new purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 95:5)

Sources & evidence

ORD record
ord-f768d30a4acc4594883a851d910ddfae
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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