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

HRID 1800529

Reaction equation

HRID 1800529 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.[C:34](Cl)(=[O:37])[CH2:35][CH3:36]>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:34](=[O:37])[CH2:35][CH3:36])=[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 62324Propionyl chlorideHCID 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 59507067N-(4-chloro-2-fluoro-5-{[2-(propanoylamino)[1,3]thiazolo[5,4-b]pyridin-5-yl]oxy}phenyl)-3-(1-cyano-1-methylethyl)benzamideYield 52%

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 produced in Example C52(v) in pyridine (1.0 mL) was added propionyl chloride (29 μL, 0.332 mmol), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate (10 mL), washed with 5% aqueous sodium hydrogen carbonate solution (10 mL) and saturated brine (10 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=70/30→0/100), and the obtained solution was concentrated under reduced pressure. The residue was crystallized from ethyl acetate/hexane to give the title compound (46.7 mg, 52%) as a colorless powder.

Workup

  1. washwashed with 5% aqueous sodium hydrogen carbonate solution (10 mL) and saturated brine (10 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationThe insoluble material was filtered off
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=70/30→0/100)
  6. concentrationthe obtained solution was concentrated under reduced pressure
  7. customThe residue was crystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-dbba4ed4a15a45f6a7e5d0ca27d84e0b
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Linked notes

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