Cyclopropanecarbonyl chloride → N-[4-chloro-5-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-2-fluorophenyl]-3-(1-cyano-1-methylethyl)benzamide

HRID 1800534Notes

Reaction equation

HRID 1800534 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.[CH:34]1([C:37](Cl)=[O:38])[CH2:36][CH2:35]1>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]([CH:34]4[CH2:36][CH2:35]4)=[O:38])=[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 77637Cyclopropanecarbonyl 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 59507017N-[4-chloro-5-({2-[(cyclopropylcarbonyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-2-fluorophenyl]-3-(1-cyano-1-methylethyl)benzamideYield 44%

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 (400 mg, 0.83 mmol) produced in Example C52(v) in pyridine (4.0 mL) was added cyclopropanecarbonyl chloride (112 μL, 1.24 mmol), and the mixture was stirred at room temperature for 6 hr. Cyclopropanecarbonyl chloride (112 μL, 1.24 mmol) was further added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate (100 mL), washed with 5% aqueous sodium hydrogen carbonate solution (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 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 (190 mg, 44%) 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 (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 obtained residue was purified by basic silica gel column chromatography (hexane/ethyl acetate=70/30→0/100)
  7. concentrationthe obtained solution was concentrated under reduced pressure
  8. customThe residue was crystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-08034c5bc5e649f689027467961ac1f5
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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