1-Pyrrolidineethanamine → HCID 86732788, compound

HRID 525921Notes

Reaction equation

HRID 525921 reaction equation
[Cl:1][C:2]1[C:11]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[C:10]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[CH:9]=[C:8]2[C:3]=1[C:4](=[O:37])[C:5]([C:34]([OH:36])=O)=[CH:6][N:7]2[CH2:32][CH3:33].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>[Cl:1][C:2]1[C:11]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[C:10]([O:22][CH2:23][C:24]2[CH:25]=[CH:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=2)[CH:9]=[C:8]2[C:3]=1[C:4](=[O:37])[C:5]([C:34]([NH:78][CH2:77][CH2:76][N:71]1[CH2:75][CH2:74][CH2:73][CH2:72]1)=[O:36])=[CH:6][N:7]2[CH2:32][CH3:33]

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 86732764HCID 86732764, compound

Product 1

HCID 86732788HCID 86732788, compoundYield 66.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-chloro-1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (Example 16f) (5 g, 8.68 mmol) in N,N-Dimethylformamide (DMF) (75 mL) was added HATU (3.96 g, 10.42 mmol) and DIPEA (4.55 mL, 26.1 mmol), the resulting mixture was stirred at r.t. for 15 min. Then 2-(pyrrolidin-1-yl)ethanamine (1.502 mL, 9.55 mmol) was added and the resulting mixture was stirred at r.t. for 1 h. The mixture was concentrated and partitioned between water and DCM. The organic layer was separated and washed with water (2×), sat. NaHCO3 (aq.) and brine. The organic solution was dried over Na2SO4, and concentrated. The residue was purified by automated silica gel chromatography (CombiFlash Rf) eluting with MeOH/DCM (0-25%), followed by reverse phase chromatography (CombiFlash Rf) eluting with ACN/water (0-100%) to afford 5-chloro-1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydroquinoline-3-carboxamide (3.6 g, 5.81 mmol, 66.9% yield) as a white solid. LCMS: (M+H)+: 620.5

Workup

  1. stirringthe resulting mixture was stirred at r.t. for 1 h
  2. concentrationThe mixture was concentrated
  3. custompartitioned between water and DCM
  4. customThe organic layer was separated
  5. washwashed with water (2×), sat. NaHCO3 (aq.) and brine
  6. dry with materialThe organic solution was dried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by automated silica gel chromatography (CombiFlash Rf)
  9. washeluting with MeOH/DCM (0-25%)
  10. washeluting with ACN/water (0-100%)

Sources & evidence

ORD record
ord-5ce5f1ed73ce4d61a9288ec6f8f955a2
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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