1-Pyrrolidineethanamine → HCID 86732810, compound

HRID 525941Notes

Reaction equation

HRID 525941 reaction equation
[CH2:1]([N:3]1[C:12]2[C:7](=[C:8]([F:33])[C:9]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)=[C:10]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[CH:11]=2)[C:6](=[O:34])[C:5]([C:35](O)=[O:36])=[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](=[C:8]([F:33])[C:9]([O:23][CH2:24][C:25]3[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=3)=[C:10]([O:13][CH2:14][C:15]3[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=3)[CH:11]=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:36])=[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 86732805HCID 86732805, compound

Product 1

HCID 86732810HCID 86732810, compoundYield 63.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-ethyl-5-fluoro-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydro quinoline-3-carboxylic acid (Example 36h) (5 g, 9.85 mmol) in N,N-Dimethylformamide (DMF) (5 mL) was added HATU (5.62 g, 14.78 mmol) and DIPEA (5.16 mL, 29.6 mmol), the resulting mixture was stirred at r.t. for 30 min. Then 2-(pyrrolidin-1-yl)ethanamine (1.861 mL, 14.78 mmol) was added and the resulting mixture was stirred at r.t. overnight. The mixture was concentrated and the residue was purified by normal phase automatic silica column chromatography (Combiflash RF) eluting with MeOH/DCM (0-20%). The product was further purified by reverse phase automatic chromatography (Combinflash RF), using a 150 g golden C18 column and eluting with acetonitrile/Water (0%-100%) to afford 1-ethyl-5-fluoro-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydroquinoline-3-carboxamide (3.8 g, 6.29 mmol, 63.9% yield) as pale yellow solid. LCMS: (M+H)+: 604.4.

Workup

  1. stirringthe resulting mixture was stirred at r.t. overnight
  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%)
  5. customThe product was further purified by reverse phase automatic chromatography (Combinflash RF)
  6. washeluting with acetonitrile/Water (0%-100%)

Sources & evidence

ORD record
ord-5e94de4306f64b48b48f1280c92479ee
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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