Cyclopropanecarbonyl chloride → HCID 59506937, compound

HRID 1800515Notes

Reaction equation

HRID 1800515 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[CH:13]=[C:14]([NH:19][C:20](=[O:32])[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([C:30]#[N:31])([CH3:29])[CH3:28])[CH:22]=3)[CH:15]=[CH:16][C:17]=1[Cl:18])[N:5]=2.[CH:33]1([C:36](Cl)=[O:37])[CH2:35][CH2:34]1>N1C=CC=CC=1>[Cl:18][C:17]1[CH:16]=[CH:15][C:14]([NH:19][C:20](=[O:32])[C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([C:30]#[N:31])([CH3:28])[CH3:29])[CH:22]=2)=[CH:13][C:12]=1[O:11][C:6]1[N:5]=[C:4]2[S:3][C:2]([NH:1][C:36]([CH:33]3[CH2:35][CH2:34]3)=[O:37])=[N:10][C:9]2=[CH:8][CH:7]=1

Participants

4

Reactant 2

HCID 77637Cyclopropanecarbonyl chlorideHCID 86646013N-{3-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-chlorophenyl}-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 59506937HCID 59506937, compoundYield 46.2%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of N-{3-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-4-chlorophenyl}-3-(1-cyano-1-methylethyl)benzamide (464 mg, 1.00 mmol) in pyridine (10 mL) was added cyclopropanecarbonyl chloride (181 μL, 2.00 mmol), and the mixture was stirred at room temperature for 12 hr. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with ethyl acetate (50 mL), washed with 5% aqueous sodium hydrogen carbonate solution (50 mL) and saturated brine (50 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=60/40→0/100), and the obtained solution was concentrated under reduced pressure. The residue was crystallized from ethyl acetate/hexane to give the title compound (246 mg, 46%) as a colorless powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionthe residue was diluted with ethyl acetate (50 mL)
  3. washwashed with 5% aqueous sodium hydrogen carbonate solution (50 mL) and saturated brine (50 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationThe insoluble material was filtered off
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=60/40→0/100)
  8. concentrationthe obtained solution was concentrated under reduced pressure
  9. customThe residue was crystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-4686dc20fd2244af92323ab6359544c3
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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