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

HRID 1800525Notes

Reaction equation

HRID 1800525 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[C:9]([N:10]=1)=[CH:8][CH:7]=[C:6]([O:11][C:12]1[C:13]([Cl:33])=[CH:14][C:15]([F:32])=[C:16]([NH:18][C:19](=[O:31])[C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([C:29]#[N:30])([CH3:28])[CH3:27])[CH:21]=3)[CH:17]=1)[N:5]=2.[CH3:34][O:35][CH2:36][C:37](Cl)=[O:38]>N1C=CC=CC=1.C(OCC)(=O)C>[Cl:33][C:13]1[C:12]([O:11][C:6]2[N:5]=[C:4]3[S:3][C:2]([NH:1][C:37](=[O:38])[CH2:36][O:35][CH3:34])=[N:10][C:9]3=[CH:8][CH:7]=2)=[CH:17][C:16]([NH:18][C:19](=[O:31])[C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([C:29]#[N:30])([CH3:28])[CH3:27])[CH:21]=2)=[C:15]([F:32])[CH:14]=1

Participants

5

Reactant 2

HCID 96623Methoxyacetyl chloride2×HCID 86646015N-(5-[(2-Amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-chloro-2-fluorophenyl}-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 59506972N-[4-chloro-2-fluoro-5-({2-[(methoxyacetyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)phenyl]-3-(1-cyano-1-methylethyl)benzamideYield 65%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-chloro-2-fluorophenyl}-3-(1-cyano-1-methylethyl)benzamide (100 mg, 0.207 mmol) produced in Example C52(v) in pyridine (2.0 mL) was added methoxyacetyl chloride (30 μL, 0.331 mmol), and the mixture was stirred at room temperature for 2 hr. Methoxyacetyl chloride (15 μL, 0.165 mmol) was further added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate (25 mL), washed with 5% aqueous sodium hydrogen carbonate solution (25 mL) and saturated brine (25 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 (hexane/ethyl acetate=70/30→20/80), and the obtained solution was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/hexane to give the title compound (74.5 mg, 65%) as a colorless powder.

Workup

  1. stirringthe mixture was stirred at room temperature for 2 hr
  2. washwashed with 5% aqueous sodium hydrogen carbonate solution (25 mL) and saturated brine (25 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 (hexane/ethyl acetate=70/30→20/80)
  7. concentrationthe obtained solution was concentrated under reduced pressure
  8. customThe residue was recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-4354773a639f4a879ad99c51c728b9cf
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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