Triethylamine → N-{3-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]propyl}-2-[4-(2-methoxyethyl)piperazin-1-yl]acetamide hydrochloride

HRID 1474542Notes

Reaction equation

HRID 1474542 reaction equation
[Cl:1][CH2:2][C:3]([NH:5][CH2:6][CH2:7][CH2:8][N:9]1[C:18]2[C:13](=[C:14]([F:23])[CH:15]=[CH:16][C:17]=2[O:19][CH2:20][CH2:21][CH3:22])[C:12](=[O:24])[C:11]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)=[CH:10]1)=[O:4].[CH3:33][O:34][CH2:35][CH2:36][N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.C(N(CC)CC)C>C(#N)C>[ClH:1].[F:23][C:14]1[CH:15]=[CH:16][C:17]([O:19][CH2:20][CH2:21][CH3:22])=[C:18]2[C:13]=1[C:12](=[O:24])[C:11]([C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=1)=[CH:10][N:9]2[CH2:8][CH2:7][CH2:6][NH:5][C:3](=[O:4])[CH2:2][N:40]1[CH2:41][CH2:42][N:37]([CH2:36][CH2:35][O:34][CH3:33])[CH2:38][CH2:39]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27346381-(2-Methoxyethyl)piperazineHCID 584925612-chloro-N-{3-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]propyl}acetamide

Product 1

HCID 67418069N-{3-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]propyl}-2-[4-(2-methoxyethyl)piperazin-1-yl]acetamide hydrochlorideYield 41.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
75 °C

Procedure

2-Chloro-N-{3-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]propyl}acetamide (370 mg, 0.8 mmol) was suspended in acetonitrile (12 ml). 1-(2-Methoxyethyl)piperazine (138 mg, 0.96 mmol), triethylamine (162 mg, 1.6 mmol) and acetonitrile (2 ml) were added to the suspension, and stirred at 70 to 80° C. for 6 hours. The resulting mixture was concentrated under reduced pressure, and the residue was subjected to extraction using ethyl acetate. The extract was then sequentially washed with water, an aqueous saturated sodium chloride solution, and an aqueous saturated sodium bicarbonate solution. The washed product was concentrated under reduced pressure, and 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 then dissolved in ethyl acetate (5 ml). A 4N hydrogen chloride ethyl acetate solution (0.19 ml) was added thereto and stirred, and then the mixture was concentrated to dryness under reduced pressure, giving a pale yellow amorphous solid of N-{3-[5-fluoro-3-(4-methoxyphenyl)-4-oxo-8-propoxy-4H-quinolin-1-yl]propyl}-2-[4-(2-methoxyethyl)piperazin-1-yl]acetamide hydrochloride (200 mg).

Workup

  1. concentrationThe resulting mixture was concentrated under reduced pressure
  2. extractionthe residue was subjected to extraction
  3. washThe extract was then sequentially washed with water
  4. concentrationThe washed product was concentrated under reduced pressure
  5. customthe residue was purified
  6. concentrationThe purified product was concentrated under reduced pressure
  7. dissolutionthe residue was then dissolved in ethyl acetate (5 ml)
  8. additionA 4N hydrogen chloride ethyl acetate solution (0.19 ml) was added
  9. stirringstirred
  10. concentrationthe mixture was concentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-9eff8431743a487d876ac09e50b7008d
Source dataset
uspto-grants-2015_04
Patent number
US09018229B2

Reaction notes

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