Chloroacetyl chloride → HCID 57749192, compound

HRID 1874613Notes

Reaction equation

HRID 1874613 reaction equation
[NH2:1][C:2]1[N:32]=[C:5]2[CH:6]=[CH:7][C:8]([O:10][C:11]3[CH:12]=[C:13]([NH:18][C:19](=[O:31])[C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([C:29]#[N:30])([CH3:28])[CH3:27])[CH:21]=4)[CH:14]=[CH:15][C:16]=3[CH3:17])=[CH:9][N:4]2[N:3]=1.Cl[CH2:34][C:35](Cl)=[O:36].C(N(CC)CC)C.[CH3:45][N:46]1[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]1.C(=O)([O-])O.[Na+]>CN(C)C=O.O>[C:29]([C:26]([C:22]1[CH:21]=[C:20]([CH:25]=[CH:24][CH:23]=1)[C:19]([NH:18][C:13]1[CH:14]=[CH:15][C:16]([CH3:17])=[C:11]([O:10][C:8]2[CH:7]=[CH:6][C:5]3[N:4]([N:3]=[C:2]([NH:1][C:35](=[O:36])[CH2:34][N:49]4[CH2:50][CH2:51][N:46]([CH3:45])[CH2:47][CH2:48]4)[N:32]=3)[CH:9]=2)[CH:12]=1)=[O:31])([CH3:28])[CH3:27])#[N:30]

Participants

8

Reactant 5

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 531671-MethylpiperazineHCID 516892Sodium BicarbonateHCID 68985382N-{3-[(2-amino[1,2,4]triazolo[1,5-a]pyridin-6-yl)oxy]-4-methylphenyl}-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 57749192HCID 57749192, compoundYield 64.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of N-{3-[(2-amino[1,2,4]triazolo[1,5-a]pyridin-6-yl)oxy]-4-methylphenyl}-3-(1-cyano-1-methylethyl)benzamide (202 mg, 0.474 mmol) in N,N-dimethylformamide (5 mL) was added chloroacetyl chloride (76 μL, 0.948 mmol), and the mixture was stirred at room temperature for 4 hr. Water (15 mL) was added to the reaction mixture, and extracted with ethyl acetate (20 mL, 2×10 mL). The combined organic layer was washed with 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 residue was dissolved in tetrahydrofuran (5 mL). Triethylamine (197 μL, 1.42 mmol) and 1-methylpiperazine (158 μL, 1.42 mmol) were added, and the mixture was stirred at 60° C. for 19 hr. A saturated aqueous sodium hydrogen carbonate solution (10 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (20 mL). The organic layer was washed with 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 silica gel column chromatography (NH silica gel, ethyl acetate/methanol=100/0→94/6), and fractions containing the desired product were concentrated under reduced pressure. Diisopropyl ether was added to the obtained residue. The obtained precipitate was collected by filtration and dried to give the title compound (173 mg, 64%) as a colorless powder.

Workup

  1. extractionextracted with ethyl acetate (20 mL, 2×10 mL)
  2. washThe combined organic layer was washed with saturated brine (10 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. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
  7. stirringthe mixture was stirred at 60° C. for 19 hr
  8. extractionthe mixture was extracted with ethyl acetate (20 mL)
  9. washThe organic layer was washed with saturated brine (10 mL)
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationThe insoluble material was filtered off
  12. concentrationthe filtrate was concentrated under reduced pressure
  13. customThe obtained residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/methanol=100/0→94/6), and fractions
  14. additioncontaining the desired product
  15. concentrationwere concentrated under reduced pressure
  16. additionDiisopropyl ether was added to the obtained residue
  17. filtrationThe obtained precipitate was collected by filtration
  18. customdried

Sources & evidence

ORD record
ord-a7928332c2bc4231a3f03c5277374e13
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Reaction notes

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