Chloroacetyl chloride → HCID 57749307, compound

HRID 1874614Notes

Reaction equation

HRID 1874614 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.[NH:45]1[CH2:50][CH2:49][O:48][CH2:47][CH2:46]1>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:45]4[CH2:50][CH2:49][O:48][CH2:47][CH2:46]4)[N:32]=3)[CH:9]=2)[CH:12]=1)=[O:31])([CH3:28])[CH3:27])#[N:30]

Participants

7

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 8083MorpholineHCID 8471TriethylamineHCID 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 57749307HCID 57749307, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 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 (199 mg, 0.468 mmol) in N,N-dimethylformamide (5 mL) was added chloroacetyl chloride (76 μL, 0.842 mmol), and the mixture was stirred at room temperature for 1 hr. Water (15 mL) was added to the reaction mixture, and extracted with ethyl acetate (20 mL, 2×5 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 obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=40/60→20/80), and fractions containing the desired product were concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (5 mL). Triethylamine (195 μL, 1.40 mmol) and morpholine (122 μL, 1.40 mmol) were added, and the mixture was stirred at 60° C. for 3 hr. Water (20 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (20 mL, 2×5 mL). The combined organic layer was washed with saturated brine (5 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→99/1), 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 over to give the title compound (144 mg, 56%) as a colorless powder.

Workup

  1. extractionextracted with ethyl acetate (20 mL, 2×5 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. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=40/60→20/80), and fractions
  7. additioncontaining the desired product
  8. concentrationwere concentrated under reduced pressure
  9. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
  10. stirringthe mixture was stirred at 60° C. for 3 hr
  11. extractionthe mixture was extracted with ethyl acetate (20 mL, 2×5 mL)
  12. washThe combined organic layer was washed with saturated brine (5 mL)
  13. dry with materialdried over anhydrous sodium sulfate
  14. filtrationThe insoluble material was filtered off
  15. concentrationthe filtrate was concentrated under reduced pressure
  16. customThe obtained residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/methanol=100/0→99/1), and fractions
  17. additioncontaining the desired product
  18. concentrationwere concentrated under reduced pressure
  19. additionDiisopropyl ether was added to the obtained residue
  20. filtrationThe obtained precipitate was collected by filtration
  21. customdried over

Sources & evidence

ORD record
ord-60a68d5f02a641e39f80b20d6c20a097
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Reaction notes

Loading…