Methyl iodide → Tert-butyl 4-methoxy-4-((2-(7-methyl-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)methyl)piperidine-1-carboxylate

HRID 876512Notes

Reaction equation

HRID 876512 reaction equation
[OH:1][C:2]1([CH2:15][O:16][C:17]2[CH:18]=[CH:19][CH:20]=[C:21]3[C:26]=2[N:25]=[C:24]([C:27]2[N:31]4[CH:32]=[CH:33][C:34]([CH3:36])=[CH:35][C:30]4=[N:29][N:28]=2)[CH:23]=[CH:22]3)[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[H-].[Na+].I[CH3:40]>CN(C)C=O>[CH3:40][O:1][C:2]1([CH2:15][O:16][C:17]2[CH:18]=[CH:19][CH:20]=[C:21]3[C:26]=2[N:25]=[C:24]([C:27]2[N:31]4[CH:32]=[CH:33][C:34]([CH3:36])=[CH:35][C:30]4=[N:29][N:28]=2)[CH:23]=[CH:22]3)[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:13])([CH3:12])[CH3:14])=[O:9])[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 67234438Tert-butyl 4-hydroxy-4-((2-(7-methyl-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)methyl)piperidine-1-carboxylate

Product 1

HCID 67234513Tert-butyl 4-methoxy-4-((2-(7-methyl-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)methyl)piperidine-1-carboxylateYield 49.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of tert-butyl 4-hydroxy-4-((2-(7-methyl-[1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)methyl)piperidine-1-carboxylate (50 mg, 0.10 mmol) and sodium hydride (18 mg, 0.82 mmol) in dimethylformamide (1 mL) was stirred at ambient temperature for 15 minutes. Iodomethane (0.051 mL, 0.82 mmol) was added and the solution was stirred at ambient temperature overnight. The reaction was concentrated under reduced pressure. The residue was dissolved in dichloromethane and washed twice with saturated aqueous ammonium carbonate. The organic phase was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was triturated with hexanes and further purified by preparative thin layer chromatography with 1:9 methanol/dichloromethane to provide 25 mg (46%) of desired product.

Workup

  1. stirringthe solution was stirred at ambient temperature overnight
  2. concentrationThe reaction was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in dichloromethane
  4. washwashed twice with saturated aqueous ammonium carbonate
  5. dry with materialThe organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was triturated with hexanes
  9. customfurther purified by preparative thin layer chromatography with 1:9 methanol/dichloromethane

Sources & evidence

ORD record
ord-a70c6465cc4a4074a6dcb04ad5268813
Source dataset
uspto-grants-2015_03
Patent number
US08987251B2

Reaction notes

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