1-Hydroxybenzotriazole → 2-[5-fluoro-3-(4-hydroxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]-N-(2-morpholin-4-ylethyl)acetamide

HRID 1874057Notes

Reaction equation

HRID 1874057 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[F:32][C:33]1[CH:42]=[CH:41][C:40]([O:43][CH2:44][CH2:45][CH3:46])=[C:39]2[C:34]=1[C:35](=[O:58])[C:36]([C:51]1[CH:56]=[CH:55][C:54]([OH:57])=[CH:53][CH:52]=1)=[CH:37][N:38]2[CH2:47][C:48](O)=[O:49]>C(N(CC)CC)C.O.CN(C=O)C>[F:32][C:33]1[CH:42]=[CH:41][C:40]([O:43][CH2:44][CH2:45][CH3:46])=[C:39]2[C:34]=1[C:35](=[O:58])[C:36]([C:51]1[CH:52]=[CH:53][C:54]([OH:57])=[CH:55][CH:56]=1)=[CH:37][N:38]2[CH2:47][C:48]([NH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1)=[O:49]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 4082852-MorpholinoethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 58492574[5-fluoro-3-(4-hydroxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]acetic acid

Product 1

HCID 674164372-[5-fluoro-3-(4-hydroxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]-N-(2-morpholin-4-ylethyl)acetamideYield 24.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

4-(2-Aminoethyl)morpholine (184 mg, 1.41 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (WSC, 295 mg, 1.54 mmol) and 1-hydroxybenzotriazole (HOBT, 215 mg, 1.41 mmol) were added to a DMF solution (7 ml) of [5-fluoro-3-(4-hydroxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]acetic acid (500 mg, 1.34 mmol) and then the mixture was stirred at room temperature for 23 hours. Water and triethylamine were added to the reaction mixture to make the reaction mixture basic, followed by extraction using ethyl acetate. The thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution, and then concentrated under reduced pressure. The residue was purified using silica gel column chromatography (dichloromethane:methanol=30:1→10:1). The purified product was concentrated under reduced pressure, and the residue was recrystallized from ethyl acetate, giving a white powder of 2-[5-fluoro-3-(4-hydroxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]-N-(2-morpholin-4-ylethyl)acetamide (157 mg, yield: 24%).

Workup

  1. extractionfollowed by extraction
  2. washThe thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified
  5. concentrationThe purified product was concentrated under reduced pressure
  6. customthe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-81cc3dd712524bc8921b04dc9c4efb3e
Source dataset
uspto-grants-2012_11
Patent number
US08304546B2

Reaction notes

Loading…