Chloroacetyl chloride → 3-(1-cyano-1-methylethyl)-N-{3-[(2-{[(4-methylpiperazin-1-yl)acetyl]amino}-7-nitro-1,3-benzothiazol-6-yl)oxy]phenyl}benzamide

HRID 455218Notes

Reaction equation

HRID 455218 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[C:10]([N+:11]([O-:13])=[O:12])=[C:9]([O:14][C:15]3[CH:16]=[C:17]([NH:21][C:22](=[O:34])[C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([C:32]#[N:33])([CH3:31])[CH3:30])[CH:24]=4)[CH:18]=[CH:19][CH:20]=3)[CH:8]=[CH:7][C:5]=2[N:6]=1.Cl[CH2:36][C:37](Cl)=[O:38].C(N(CC)CC)C.[CH3:47][N:48]1[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]1>CC(N(C)C)=O.C(OCC)(=O)C>[C:32]([C:29]([C:25]1[CH:24]=[C:23]([CH:28]=[CH:27][CH:26]=1)[C:22]([NH:21][C:17]1[CH:18]=[CH:19][CH:20]=[C:15]([O:14][C:9]2[CH:8]=[CH:7][C:5]3[N:6]=[C:2]([NH:1][C:37](=[O:38])[CH2:36][N:51]4[CH2:52][CH2:53][N:48]([CH3:47])[CH2:49][CH2:50]4)[S:3][C:4]=3[C:10]=2[N+:11]([O-:13])=[O:12])[CH:16]=1)=[O:34])([CH3:30])[CH3:31])#[N:33]

Participants

7

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 531671-MethylpiperazineHCID 86644697N-{3-[(2-amino-7-nitro-1,3-benzothiazol-6-yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 594544783-(1-cyano-1-methylethyl)-N-{3-[(2-{[(4-methylpiperazin-1-yl)acetyl]amino}-7-nitro-1,3-benzothiazol-6-yl)oxy]phenyl}benzamideYield 84%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolvent2×HCID 31374DimethylacetamideSolvent

Procedure

To a solution of N-{3-[(2-amino-7-nitro-1,3-benzothiazol-6-yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamide (150 mg, 0.32 mmol) produced in Example 37(ii) in dimethylacetamide (2 mL) was added chloroacetyl chloride (55 μL, 0.70 mmol), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate (25 mL), washed successively with 5% aqueous sodium hydrogen carbonate solution (25 mL) and saturated brine (25 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, the filtrate was concentrated under reduced pressure, the obtained residue was dissolved in tetrahydrofuran (3 mL). Triethylamine (130 μL, 0.95 mmol) and 1-methylpiperazine (105 μL, 0.95 mmol) were added to the mixture, and the mixture was stirred at 60° C. for 4 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (25 mL), washed successively with water (25 mL) and saturated brine (25 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, the filtrate was concentrated under reduced pressure, the obtained residue was purified by basic silica gel column chromatography (methanol/ethyl acetate=0/100→15/85), and the obtained solution was concentrated under reduced pressure. The residue was crystallized from ethyl acetate/diisopropyl ether to give the title compound (162 mg, 84%) as a yellow powder.

Workup

  1. washwashed successively with 5% aqueous sodium hydrogen carbonate solution (25 mL) and saturated brine (25 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationInsoluble material was filtered off
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. dissolutionthe obtained residue was dissolved in tetrahydrofuran (3 mL)
  6. stirringthe mixture was stirred at 60° C. for 4 hr
  7. temperatureThe reaction mixture was cooled to room temperature
  8. washwashed successively with water (25 mL) and saturated brine (25 mL)
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationInsoluble material was filtered off
  11. concentrationthe filtrate was concentrated under reduced pressure
  12. customthe obtained residue was purified by basic silica gel column chromatography (methanol/ethyl acetate=0/100→15/85)
  13. concentrationthe obtained solution was concentrated under reduced pressure
  14. customThe residue was crystallized from ethyl acetate/diisopropyl ether

Sources & evidence

ORD record
ord-dd83365c3d5a40efb7d3a3f180e3077b
Source dataset
uspto-grants-2013_07
Patent number
US08497274B2

Reaction notes

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