Sodium hydride → 3-((6-amino-9H-purin-9-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one

HRID 1627204Notes

Reaction equation

HRID 1627204 reaction equation
[N:1]1[C:9]([NH2:10])=[C:8]2[C:4]([NH:5][CH:6]=[N:7]2)=[N:3][CH:2]=1.[H-].[Na+].Br[CH2:14][C:15]1[N:16]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:33])[C:17](=[O:26])[C:18]2[C:23]([CH:24]=1)=[CH:22][CH:21]=[CH:20][C:19]=2[CH3:25]>CN(C=O)C>[NH2:10][C:9]1[N:1]=[CH:2][N:3]=[C:4]2[C:8]=1[N:7]=[CH:6][N:5]2[CH2:14][C:15]1[N:16]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:33])[C:17](=[O:26])[C:18]2[C:23]([CH:24]=1)=[CH:22][CH:21]=[CH:20][C:19]=2[CH3:25]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 580086503-(Bromomethyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-oneHCID 178508693HCID 178508693, compound

Product 1

HCID 580086983-((6-amino-9H-purin-9-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-oneYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

9H-Purin-6-amine (1901) (540 mg, 4.0 mmol) was dissolved in anhydrous DMF (20 mL). NaH (60% in mineral oil, 160 mg, 4.0 mmol) was added and the resulting mixture was stirred at RT for 30 min. 3-(Bromomethyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one (1610) (1.37 g, 4.0 mmol) was added. The reaction mixture was stirred at RT for 30 min, poured into ice-water (30 mL) and then extracted with ethyl acetate (3×50 mL). The combined organic layer was washed with brine (25 mL), dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (2-20% MeOH/DCM) to afford the desired product, 3-((6-amino-9H-purin-9-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one (1902) (1.1 g, 70% yield) as a white solid.

Workup

  1. stirringThe reaction mixture was stirred at RT for 30 min
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. washThe combined organic layer was washed with brine (25 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by flash column chromatography on silica gel (2-20% MeOH/DCM)

Sources & evidence

ORD record
ord-26b71e9019fb4fe9853935adee1c965f
Source dataset
uspto-grants-2014_07
Patent number
US08785456B2

Reaction notes

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