1-Pyrrolidineethanamine → 1-ethyl-5-hydroxy-6-((4-methoxybenzyl)oxy)-4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydroquinoline-3-carboxamide

HRID 525962Notes

Reaction equation

HRID 525962 reaction equation
[CH2:1]([N:3]1[C:12]2[C:7](=[C:8]([OH:23])[C:9]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)=[CH:10][CH:11]=2)[C:6](=[O:24])[C:5]([C:25](O)=[O:26])=[CH:4]1)[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[N:61]1([CH2:66][CH2:67][NH2:68])[CH2:65][CH2:64][CH2:63][CH2:62]1>CN(C)C=O>[CH2:1]([N:3]1[C:12]2[C:7](=[C:8]([OH:23])[C:9]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)=[CH:10][CH:11]=2)[C:6](=[O:24])[C:5]([C:25]([NH:68][CH2:67][CH2:66][N:61]2[CH2:65][CH2:64][CH2:63][CH2:62]2)=[O:26])=[CH:4]1)[CH3:2]

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 867328281-Ethyl-5-hydroxy-6-((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

Product 1

HCID 867328291-ethyl-5-hydroxy-6-((4-methoxybenzyl)oxy)-4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydroquinoline-3-carboxamideYield 56.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-ethyl-5-hydroxy-6-((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (1.4 g, 3.79 mmol) in N,N-Dimethylformamide (DMF) (30 mL) was added HATU (1.729 g, 4.55 mmol) and DIPEA (1.655 mL, 9.48 mmol), the resulting mixture was stirred at r.t. for 30 min. Then 2-(pyrrolidin-1-yl)ethanamine (0.656 mL, 4.17 mmol) was added and the resulting mixture was stirred at r.t. for 3 h. The reaction mixture was concentrated and the residue was dissolved in DCM and washed with water, sat. NaHCO3 (aq.) and brine. The organic layer was separated and concentrated, the residue was purified by normal phase silica gel chromatography (CombiFlash), eluting with MeOH/DCM (0-20%) to afford 1-ethyl-5-hydroxy-6-((4-methoxybenzyl)oxy)-4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydroquinoline-3-carboxamide (1 g, 2.148 mmol, 56.7% yield) as a yellow solid. LCMS: (M+H)+: 466.3.

Workup

  1. stirringthe resulting mixture was stirred at r.t. for 3 h
  2. concentrationThe reaction mixture was concentrated
  3. dissolutionthe residue was dissolved in DCM
  4. washwashed with water, sat. NaHCO3 (aq.) and brine
  5. customThe organic layer was separated
  6. concentrationconcentrated
  7. customthe residue was purified by normal phase silica gel chromatography (CombiFlash)
  8. washeluting with MeOH/DCM (0-20%)

Sources & evidence

ORD record
ord-d4f72c11f44f49a49dd57b410b955568
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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