Triethylamine → 3-(1-cyano-1-methylethyl)-N-{2-methyl-5-[(2-{[(4-methylpiperazin-1-yl)acetyl]amino}-1,3-benzothiazol-6-yl)oxy]phenyl}benzamide

HRID 2190384Notes

Reaction equation

HRID 2190384 reaction equation
Cl[CH2:2][C:3]([NH:5][C:6]1[S:7][C:8]2[CH:14]=[C:13]([O:15][C:16]3[CH:17]=[CH:18][C:19]([CH3:36])=[C:20]([NH:22][C:23](=[O:35])[C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([C:33]#[N:34])([CH3:32])[CH3:31])[CH:25]=4)[CH:21]=3)[CH:12]=[CH:11][C:9]=2[N:10]=1)=[O:4].C(N(CC)CC)C.[CH3:44][N:45]1[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]1>O1CCCC1.C(OCC)(=O)C>[C:33]([C:30]([C:26]1[CH:25]=[C:24]([CH:29]=[CH:28][CH:27]=1)[C:23]([NH:22][C:20]1[CH:21]=[C:16]([O:15][C:13]2[CH:12]=[CH:11][C:9]3[N:10]=[C:6]([NH:5][C:3](=[O:4])[CH2:2][N:48]4[CH2:49][CH2:50][N:45]([CH3:44])[CH2:46][CH2:47]4)[S:7][C:8]=3[CH:14]=2)[CH:17]=[CH:18][C:19]=1[CH3:36])=[O:35])([CH3:32])[CH3:31])#[N:34]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 531671-MethylpiperazineHCID 86655359N-[5-({2-[(chloroacetyl)amino]-1,3-benzothiazol-6-yl}oxy)-2-methylphenyl]-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 866553603-(1-cyano-1-methylethyl)-N-{2-methyl-5-[(2-{[(4-methylpiperazin-1-yl)acetyl]amino}-1,3-benzothiazol-6-yl)oxy]phenyl}benzamideYield 40%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

N-[5-({2-[(Chloroacetyl)amino]-1,3-benzothiazol-6-yl}oxy)-2-methylphenyl]-3-(1-cyano-1-methylethyl)benzamide synthesized above was dissolved in tetrahydrofuran (8.0 mL), triethylamine (155 μL, 1.13 mmol) and 1-methylpiperazine (100 μL, 0.902 mmol) were added, and the mixture was stirred at 60° C. for 8 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (100 mL), washed with water (50 mL×2) and saturated brine (50 mL), successively, and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=50/50→0/100), and the obtained solution was concentrated under reduced pressure. The residue was triturated with ethyl acetate/hexane to give the title compound (106 mg, 40%) as a colorless solid.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with water (50 mL×2) and saturated brine (50 mL)
  3. dry with materialsuccessively, and dried over anhydrous sodium sulfate
  4. filtrationThe insoluble material was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=50/50→0/100)
  7. concentrationthe obtained solution was concentrated under reduced pressure
  8. customThe residue was triturated with ethyl acetate/hexane

Sources & evidence

ORD record
ord-a0fbfcb215404c32987a57f0dbe3992f
Source dataset
uspto-grants-2012_12
Patent number
US08324395B2

Reaction notes

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