Triethylamine → 3-((4-methoxybenzyl)oxy)-1-methyl-4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydroquinolin-8-carboxamide

HRID 525884Notes

Reaction equation

HRID 525884 reaction equation
[CH3:1][O:2][C:3]1[CH:25]=[CH:24][C:6]([CH2:7][O:8][C:9]2[C:18](=[O:19])[C:17]3[C:12](=[C:13]([C:20]([NH2:22])=[O:21])[CH:14]=[CH:15][CH:16]=3)[N:11]([CH3:23])[CH:10]=2)=[CH:5][CH:4]=1.[H-].[Na+].Cl.Cl[CH2:30][CH2:31][N:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1.C(N(CC)CC)C>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][O:8][C:9]2[C:18](=[O:19])[C:17]3[C:12](=[C:13]([C:20]([NH:22][CH2:30][CH2:31][N:32]4[CH2:36][CH2:35][CH2:34][CH2:33]4)=[O:21])[CH:14]=[CH:15][CH:16]=3)[N:11]([CH3:23])[CH:10]=2)=[CH:24][CH:25]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24758Sodium hydride2×HCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 867327503-((4-Methoxybenzyl)oxy)-1-methyl-4-oxo-1,4-dihydroquinolin-8-carboxamide

Product 1

HCID 867327513-((4-methoxybenzyl)oxy)-1-methyl-4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydroquinolin-8-carboxamideYield 21.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 3-((4-methoxybenzyl)oxy)-1-methyl-4-oxo-1,4-dihydroquinoline-8-carboxamide (1.09 g, 3.22 mmol) in N,N-dimethylformamide (30 mL) was added sodium hydride (0.193 g, 4.83 mmol) and the mixture was stirred at room temperature for 1 h. Then the mixture of 1-(2-chloroethyl)pyrrolidine, Hydrochloride (0.548 g, 3.22 mmol) and triethylamine (0.494 mL, 3.54 mmol) in N,N-dimethylformamide (30.0 mL) was added in one portion. The resulting mixture was stirred at 50° C. for 3.5 h. Extra NaH (0.15 eq) was added, the mixture was stirred at 50° C. for another 0.5 h. The solvent was removed in vacuo, and the residue was partitioned between water (50 mL) and dichloromethane (50 mL), and extracted with DCM for three times. The combined organic phases were dried over sodium sulfate, filtered, and concentrated. The light yellow residue was purified by automatic silica gel column chromatography (Combiflash RF), eluting with [CH2Cl2/MeOH/NH4OH (80:20:2)]/CH2Cl2 (0-50%) to afford 3-((4-methoxybenzyl)oxy)-1-methyl-4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydroquinoline-8-carboxamide (0.3 g, 0.689 mmol, 21.38% yield) as a light brown oil. LCMS: (M+H)+: 436.3.

Workup

  1. additionwas added in one portion
  2. stirringThe resulting mixture was stirred at 50° C. for 3.5 h
  3. stirringthe mixture was stirred at 50° C. for another 0.5 h
  4. customThe solvent was removed in vacuo
  5. customthe residue was partitioned between water (50 mL) and dichloromethane (50 mL)
  6. extractionextracted with DCM for three times
  7. dry with materialThe combined organic phases were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe light yellow residue was purified by automatic silica gel column chromatography (Combiflash RF)
  11. washeluting with [CH2Cl2/MeOH/NH4OH (80:20:2)]/CH2Cl2 (0-50%)

Sources & evidence

ORD record
ord-7e277986c103475fb3a536e24f61cf20
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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