Chloroacetyl chloride → N-[5-({2-[(chloroacetyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-2-methylphenyl]-3-(1-cyanocyclopropyl)benzamide

HRID 1800455Notes

Reaction equation

HRID 1800455 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]=[CH:14][C:15]([CH3:32])=[C:16]([NH:18][C:19](=[O:31])[C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]4([C:29]#[N:30])[CH2:28][CH2:27]4)[CH:21]=3)[CH:17]=1)[N:5]=2.[Cl:33][CH2:34][C:35](Cl)=[O:36]>CN(C)C=O.C(OCC)(=O)C>[Cl:33][CH2:34][C:35]([NH: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]=[CH:14][C:15]([CH3:32])=[C:16]([NH:18][C:19](=[O:31])[C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]4([C:29]#[N:30])[CH2:27][CH2:28]4)[CH:21]=3)[CH:17]=1)[N:5]=2)=[O:36]

Participants

5

Reactant 2

HCID 6577Chloroacetyl chlorideHCID 86645998N-{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-2-methylphenyl)-3-(1-cyanocyclopropyl)benzamide

Product 1

HCID 86645999N-[5-({2-[(chloroacetyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-2-methylphenyl]-3-(1-cyanocyclopropyl)benzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-2-methylphenyl}-3-(1-cyanocyclopropyl)benzamide (200 mg, 0.453 mmol) produced in Example C29(iv) in N,N-dimethylformamide (4.0 mL) was added chloroacetyl chloride (54 μL, 0.68 mmol), 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 silica gel column chromatography (hexane/ethyl acetate=50/50→0/100), and the obtained solution was concentrated under reduced pressure to give N-[5-({2-[(chloroacetyl)amino][1,3]thiazolo[5,4-b]pyridin-5-yl}oxy)-2-methylphenyl]-3-(1-cyanocyclopropyl)benzamide as a colorless solid.

Workup

  1. washwashed with 5% aqueous sodium hydrogen carbonate solution (100 mL) and saturated brine (100 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 silica gel column chromatography (hexane/ethyl acetate=50/50→0/100)
  6. concentrationthe obtained solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-b31539e47f124ff0978b5fbf8731edab
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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