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

HRID 1474536Notes

Reaction equation

HRID 1474536 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH2:14][CH3:15])=[C:8]2[C:3]=1[C:4](=[O:28])[C:5]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1)=[CH:6][N:7]2[CH2:16][C:17]([OH:19])=O.[NH2:29][CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1.C(N(CC)CC)C.C(OP(C#N)(=O)OCC)C>O.CN(C=O)C>[F:1][C:2]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH2:14][CH3:15])=[C:8]2[C:3]=1[C:4](=[O:28])[C:5]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=1)=[CH:6][N:7]2[CH2:16][C:17]([NH:29][CH2:30][CH2:31][N:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1)=[O:19]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 4082852-MorpholinoethylamineHCID 58492398HCID 58492398, compound

Product 1

HCID 674170082-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]-N-(2-morpholin-4-ylethyl)acetamideYield 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

To a DMF solution (2 ml) of [5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]acetic acid (800 mg, 2.07 mmol) were sequentially added a DMF solution (1 ml) of 4-(2-aminoethyl)morpholine (273 mg), triethylamine (506 mg, 5.0 mmol), diethylphosphorocyanidate (DEPC, 405 mg, 2.48 mmol) and DMF (1 ml) while ice-cooling, followed by stirring at room temperature for 23 hours. Water was added to the reaction mixture and then subjected to extraction using ethyl acetate. The thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution twice, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified using silica gel column chromatography (dichloromethane:methanol=30:1→15:1). 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-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]-N-(2-morpholin-4-ylethyl)acetamide (789 mg, yield: 77%).

Workup

  1. temperaturecooling
  2. extractionsubjected to extraction
  3. washThe thus-obtained organic layer was washed with an aqueous saturated sodium chloride solution twice
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified
  7. concentrationThe purified product was concentrated under reduced pressure
  8. customthe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-1e73498d2917427e83e55213e9b8fcfa
Source dataset
uspto-grants-2015_04
Patent number
US09018229B2

Reaction notes

Loading…