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

HRID 1800524

Reaction equation

HRID 1800524 reaction equation
[Cl:1][C:2]1[C:7]([O:8][C:9]2[N:14]=[C:13]3[S:15][C:16]([NH:18][C:19](=[O:22])[CH2:20]Cl)=[N:17][C:12]3=[CH:11][CH:10]=2)=[CH:6][C:5]([NH:23][C:24](=[O:36])[C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([C:34]#[N:35])([CH3:33])[CH3:32])[CH:26]=2)=[C:4]([F:37])[CH:3]=1.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>[Cl:1][C:2]1[C:7]([O:8][C:9]2[N:14]=[C:13]3[S:15][C:16]([NH:18][C:19](=[O:22])[CH2:20][N:49]4[CH2:50][CH2:51][N:46]([CH3:45])[CH2:47][CH2:48]4)=[N:17][C:12]3=[CH:11][CH:10]=2)=[CH:6][C:5]([NH:23][C:24](=[O:36])[C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([C:34]#[N:35])([CH3:32])[CH3:33])[CH:26]=2)=[C:4]([F:37])[CH:3]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 531671-MethylpiperazineHCID 86646016N-[4-chloro-5-({2-[(chloroacetyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-2-fluorophenyl]-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 59507006N-{4-chloro-2-fluoro-5-[(2-{[(4-methylpiperazin-1-yl)acetyl]amino}[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamideYield 75%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

N-[4-Chloro-5-({2-[(chloroacetyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-2-fluorophenyl]-3-(1-cyano-1-methylethyl)benzamide synthesized above was dissolved in tetrahydrofuran (3.0 mL), triethylamine (171 μL, 1.25 mmol) and 1-methylpiperazine (138 μL, 1.25 mmol) were added, and the mixture was stirred at 60° C. for 4 hr. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (30 mL), washed with water (30 mL) and saturated brine (30 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→85/15), and the obtained solution was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/hexane to give the title compound (193 mg, 75%) as a colorless powder.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with water (30 mL) and saturated brine (30 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→85/15)
  7. concentrationthe obtained solution was concentrated under reduced pressure
  8. customThe residue was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-4e275145f8974014a9463a764f30599b
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Linked notes

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