1-Pyrrolidineethanamine → 5-((4-methoxybenzyl)oxy)-1-methyl-4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydropyridine-2-carboxamide

HRID 525853Notes

Reaction equation

HRID 525853 reaction equation
[CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]([CH2:7][O:8][C:9]2[C:10](=[O:19])[CH:11]=[C:12]([C:16]([OH:18])=O)[N:13]([CH3:15])[CH:14]=2)=[CH:5][CH:4]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[N:55]1([CH2:60][CH2:61][NH2:62])[CH2:59][CH2:58][CH2:57][CH2:56]1>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:10](=[O:19])[CH:11]=[C:12]([C:16]([NH:62][CH2:61][CH2:60][N:55]3[CH2:59][CH2:58][CH2:57][CH2:56]3)=[O:18])[N:13]([CH3:15])[CH:14]=2)=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 13441-PyrrolidineethanamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 708124915-((4-Methoxybenzyl)oxy)-1-methyl-4-oxo-1,4-dihydropyridine-2-carboxylic acid

Product 1

HCID 867327195-((4-methoxybenzyl)oxy)-1-methyl-4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydropyridine-2-carboxamideYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-((4-methoxybenzyl)oxy)-1-methyl-4-oxo-1,4-dihydropyridine-2-carboxylic acid (1.21 g, 4.18 mmol), HATU (1.908 g, 5.02 mmol), diisopropylethyl amine (1.5 ml, 8.59 mmol) in N,N-dimethylformamide (15.0 ml) was stirred at room temperature for 30 min. at which time 2-(pyrrolidin-1-yl)ethanamine (0.58 ml, 4.61 mmol) was added and the reaction was allowed to stir for 3 h. The reaction was concentrated under vacuum, the residue was triturated with dichloromethane. The solid material was filtered and further washed with dichloromethane. The supernatant was collected, concentrated under reduced pressure and the residue was purified on silica gel eluting with methanol/dichloromethane/ammonium hydroxide. The fractions containing the desired product were concentrated, the residue was dissolved in dichloromethane, and washed with water. The organic phase was dried with anhydrous sodium sulfate, filtered, and concentrated to give 5-((4-methoxybenzyl)oxy)-1-methyl-4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydropyridine-2-carboxamide (1.32 g, 3.42 mmol, 82% yield) as nearly white solid. LCMS: (M+H)+: 386.2

Workup

  1. additionwas added
  2. concentrationThe reaction was concentrated under vacuum
  3. customthe residue was triturated with dichloromethane
  4. filtrationThe solid material was filtered
  5. washfurther washed with dichloromethane
  6. customThe supernatant was collected
  7. concentrationconcentrated under reduced pressure
  8. customthe residue was purified on silica gel eluting with methanol/dichloromethane/ammonium hydroxide
  9. additionThe fractions containing the desired product
  10. concentrationwere concentrated
  11. dissolutionthe residue was dissolved in dichloromethane
  12. washwashed with water
  13. dry with materialThe organic phase was dried with anhydrous sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-630df1b38356478f875d3f6a3301f7f3
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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