Dimethyl Sulfate → 3,6,7-Trimethoxy-1-methyl-4-(naphthalen-2-ylmethyl)isoquinoline

HRID 1620161Notes

Reaction equation

HRID 1620161 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]([CH3:15])=[N:8][C:7]([OH:16])=[C:6]2[CH2:17][C:18]1[CH:27]=[CH:26][C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=1.[Li+].[CH3:29][Si]([N-][Si](C)(C)C)(C)C.S(OC)(OC)(=O)=O>CN(C=O)C>[CH3:29][O:16][C:7]1[N:8]=[C:9]([CH3:15])[C:10]2[C:5]([C:6]=1[CH2:17][C:18]1[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=1)=[CH:4][C:3]([O:2][CH3:1])=[C:12]([O:13][CH3:14])[CH:11]=2

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 2733832Lithium HexamethyldisilazideHCID 178486659HCID 178486659, compound

Product 1

HCID 601648003,6,7-Trimethoxy-1-methyl-4-(naphthalen-2-ylmethyl)isoquinoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6,7-dimethoxy-1-methyl-4-(naphthalen-2-ylmethyl)isoquinolin-3-ol CCH 29038 free base (58 mg, 161 μmol) in dry DMF (6 mL) at 0° C. in a 25 mL round-bottomed flask equipped with a magnetic stirrer was added LiHMDS (1.0 N in TBME, 175 μL, 175 μmol) and the mixture was stirred for 20 min at RT. Dimethyl sulphate (18 μL, 192 μmol) was then added at 0° C. and the mixture was stirred overnight at RT. The mixture was then concentrated to dryness at 40° C. under vacuum and the residue was taken up in CH2Cl2 (40 mL). 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 cyclohexane:EtOAc=100:0 to 86:14) provided 23 mg of 3,6,7-trimethoxy-1-methyl-4-(naphthalen-2-ylmethyl)isoquinoline. 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 0.50 M HCl solution in MeOH (0.4 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to afford 3,6,7-trimethoxy-1-methyl-4-(naphthalen-2-ylmethyl)isoquinoline hydrochloride 18 as a brown solid (25 mg, 38% yield).

Workup

  1. stirringthe mixture was stirred overnight at RT
  2. concentrationThe mixture was then concentrated to dryness at 40° C. under vacuum
  3. washThe organic solution was washed with brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated at 40° C. under vacuum
  7. customPurification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 86:14)

Sources & evidence

ORD record
ord-eaf537febf3a42799e8fd8b043acf3e8
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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