1-Pyrrolidineethanamine → 1-ethyl-6-fluoro-7,8-bis((4-methoxybenzyl)oxy)-4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydroquinoline-3-carboxamide

HRID 525946Notes

Reaction equation

HRID 525946 reaction equation
[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:33])=[C:10]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)[C:11]=2[O:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[C:6](=[O:34])[C:5]([C:35]([OH:37])=O)=[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:71]1([CH2:76][CH2:77][NH2:78])[CH2:75][CH2:74][CH2:73][CH2:72]1>CN(C)C=O>[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:33])=[C:10]([O:23][CH2:24][C:25]3[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=3)[C:11]=2[O:13][CH2:14][C:15]2[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=2)[C:6](=[O:34])[C:5]([C:35]([NH:78][CH2:77][CH2:76][N:71]2[CH2:75][CH2:74][CH2:73][CH2:72]2)=[O:37])=[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 867328111-Ethyl-6-fluoro-7,8-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

Product 1

HCID 867328151-ethyl-6-fluoro-7,8-bis((4-methoxybenzyl)oxy)-4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydroquinoline-3-carboxamideYield 69.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-ethyl-6-fluoro-7,8-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (Example 40a) (8 g, 15.76 mmol) in N,N-Dimethylformamide (DMF) (15 mL) was added HATU (8.99 g, 23.64 mmol) and DIPEA (8.26 mL, 47.3 mmol), the resulting mixture was stirred at r.t. for 30 min. 2-(Pyrrolidin-1-yl)ethanamine (2.98 mL, 23.64 mmol) was added and the resulting mixture was stirred at r.t. for 3 h. The mixture was concentrated and the residue was purified by normal phase automatic silica column chromatography (Combiflash RF) eluting with MeOH/DCM (0-20%) to afford 1-ethyl-6-fluoro-7,8-bis((4-methoxybenzyl)oxy)-4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydroquinoline-3-carboxamide (6.6 g, 10.93 mmol, 69.4% yield) as a pale yellow solid. LCMS: (M+H)+: 604.5.

Workup

  1. stirringthe resulting mixture was stirred at r.t. for 3 h
  2. concentrationThe mixture was concentrated
  3. customthe residue was purified by normal phase automatic silica column chromatography (Combiflash RF)
  4. washeluting with MeOH/DCM (0-20%)

Sources & evidence

ORD record
ord-157b03c13c694358885990d5f9665438
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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