Sodium hydride → 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-5-bromo-8-chloro-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one

HRID 577604Notes

Reaction equation

HRID 577604 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:13]=[C:12]([C:14]2[N:18]([CH3:19])[N:17]=[N:16][C:15]=2[CH3:20])[C:11]([Cl:21])=[C:10]2[C:5]=1[CH2:6][CH2:7][NH:8][C:9]2=[O:22].[CH2:23]([O:30][C:31]1[C:36]([CH2:37]Cl)=[C:35]([CH3:39])[CH:34]=[C:33]([CH3:40])[N:32]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CN(C)C=O>[CH2:23]([O:30][C:31]1[C:36]([CH2:37][N:8]2[CH2:7][CH2:6][C:5]3[C:10](=[C:11]([Cl:21])[C:12]([C:14]4[N:18]([CH3:19])[N:17]=[N:16][C:15]=4[CH3:20])=[CH:13][C:4]=3[Br:3])[C:9]2=[O:22])=[C:35]([CH3:39])[CH:34]=[C:33]([CH3:40])[N:32]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 612578682-(Benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridine2×HCID 867238305-bromo-8-chloro-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one

Product 1

HCID 867238312-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-5-bromo-8-chloro-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-oneYield 58.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydride (60% dispersion in mineral oil, 18 mg, 0.45 mmol) was added to an icebath chilled solution of 5-bromo-8-chloro-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one (293h, 80 mg, 0.225 mmol) in anhydrous N,N-dimethylformamide (15 mL), and the resulting mixture stirred at 0° C. for 30 minutes. Solid 2-(benzyloxy)-3-(chloromethyl)-4,6-dimethylpyridine (compound Z, 59 mg, 0.225 mmol) was added and stirring continued at 0° C. for one hour. While still cold, the reaction was quenched with water (20 mL). The resulting solution was extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with brine (5×50 mL), dried over sodium sulfate, concentrated, and purified by silica gel chromatography (eluting with 1:1 petroleum ether/ethyl acetate) to give 2-{[2-(benzyloxy)-4,6-dimethylpyridin-3-yl]methyl}-5-bromo-8-chloro-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one (293i, 76 mg, 58% yield) as a light yellow oil.

Workup

  1. stirringstirring
  2. waitcontinued at 0° C. for one hour
  3. customWhile still cold, the reaction was quenched with water (20 mL)
  4. extractionThe resulting solution was extracted with ethyl acetate (2×50 mL)
  5. washThe combined organic extracts were washed with brine (5×50 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. custompurified by silica gel chromatography (eluting with 1:1 petroleum ether/ethyl acetate)

Sources & evidence

ORD record
ord-6b0e8fd0d76041369c4f79387e935550
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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