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

HRID 1800493Notes

Reaction equation

HRID 1800493 reaction equation
Cl[CH2:2][C:3]([NH:5][C:6]1[S:7][C:8]2[C:13]([N:14]=1)=[CH:12][CH:11]=[C:10]([O:15][C:16]1[CH:17]=[C:18]([NH:24][C:25](=[O:37])[C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([C:35]#[N:36])([CH3:34])[CH3:33])[CH:27]=3)[CH:19]=[CH:20][C:21]=1[C:22]#[N:23])[N:9]=2)=[O:4].C(N(CC)CC)C.[CH3:45][N:46]1[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]1>O1CCCC1.C(OCC)(=O)C>[C:35]([C:32]([C:28]1[CH:27]=[C:26]([CH:31]=[CH:30][CH:29]=1)[C:25]([NH:24][C:18]1[CH:19]=[CH:20][C:21]([C:22]#[N:23])=[C:16]([O:15][C:10]2[N:9]=[C:8]3[S:7][C:6]([NH:5][C:3](=[O:4])[CH2:2][N:49]4[CH2:50][CH2:51][N:46]([CH3:45])[CH2:47][CH2:48]4)=[N:14][C:13]3=[CH:12][CH:11]=2)[CH:17]=1)=[O:37])([CH3:34])[CH3:33])#[N:36]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 531671-MethylpiperazineHCID 86646008N-[3-({2-[(chloroacetyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-4-cyanophenyl]-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 595069173-(1-cyano-1-methylethyl)-N-{4-cyano-3-[(2-{[(4-methylpiperazin-1-yl)acetyl]amino}[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]phenyl}benzamideYield 47%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

N-[3-({2-[(Chloroacetyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-4-cyanophenyl]-3-(1-cyano-1-methylethyl)benzamide synthesized above was dissolved in tetrahydrofuran (3.0 mL), triethylamine (136 μL, 0.99 mmol) and 1-methylpiperazine (109 μL, 0.99 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 (100 mL) and saturated brine (100 mL), 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 (ethyl acetate/methanol=100/0→80/20), and the obtained solution was concentrated under reduced pressure. The residue was triturated with ethyl acetate/diisopropyl ether/hexane to give the title compound (93 mg, 47%) as a colorless solid.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with water (100 mL) and saturated brine (100 mL)
  3. dry with materialdried 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 (ethyl acetate/methanol=100/0→80/20)
  7. concentrationthe obtained solution was concentrated under reduced pressure
  8. customThe residue was triturated with ethyl acetate/diisopropyl ether/hexane

Sources & evidence

ORD record
ord-8da9d1ed36874edb8719cabf2b92b774
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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