Triethylamine → HCID 57749258, compound

HRID 1874615Notes

Reaction equation

HRID 1874615 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][CH2:35][CH2:36][C:37](Cl)=[O:38].C(=O)([O-])O.[Na+].C(N(CC)CC)C.[CH3:52][N:53]1[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]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:37](=[O:38])[CH2:36][CH2:35][CH2:34][N:56]4[CH2:57][CH2:58][N:53]([CH3:52])[CH2:54][CH2:55]4)[N:32]=3)[CH:9]=2)[CH:12]=1)=[O:31])([CH3:28])[CH3:27])#[N:30]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 531671-Methylpiperazine2×HCID 783704-Chlorobutyryl chlorideHCID 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 57749258HCID 57749258, compoundYield 6%

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 (153 mg, 0.359 mmol) in N,N-dimethylformamide (5 mL) was added 4-chlorobutanoyl chloride (81 μL, 0.718 mmol), and the mixture was stirred at room temperature for 1 hr. A saturated aqueous sodium hydrogen carbonate solution (15 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (15 mL, 5 mL). The combined organic layer was washed with saturated brine (5 mL) and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (3 mL). Triethylamine (149 μL, 1.08 mmol) and 1-methylpiperazine (120 μL, 1.08 mmol) were added, and the mixture was stirred at 60° C. for 14 hr. 1-Methylpiperazine (399 μL, 3.59 mmol) was added to the reaction mixture, and the mixture was further stirred at 60° C. for 5 hr. Water (15 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (15 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, hexane/ethyl acetate=30/70→0/100, ethyl acetate/methanol=100/0→95/5), and fractions containing the desired product were concentrated under reduced pressure. The obtained residue was purified by preparative HPLC, and fractions containing the desired product were concentrated under reduced pressure. A saturated aqueous sodium hydrogen carbonate solution (10 mL) was added to the obtained residue, and the mixture was extracted with ethyl acetate (15 mL). The 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. Ethyl acetate and hexane were added to the obtained residue. The obtained precipitate was collected by filtration, and dried to give the title compound (12 mg, 6%) as a colorless powder.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (15 mL, 5 mL)
  2. washThe combined organic layer was washed with saturated brine (5 mL)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationThe insoluble material was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. dissolutionThe residue was dissolved in tetrahydrofuran (3 mL)
  7. stirringthe mixture was stirred at 60° C. for 14 hr
  8. stirringthe mixture was further stirred at 60° C. for 5 hr
  9. extractionthe mixture was extracted with ethyl acetate (15 mL, 2×5 mL)
  10. washThe combined organic layer was washed with saturated brine (5 mL)
  11. dry with materialdried over anhydrous sodium sulfate
  12. filtrationThe insoluble material was filtered off
  13. concentrationthe filtrate was concentrated under reduced pressure
  14. customThe obtained residue was purified by silica gel column chromatography (NH silica gel, hexane/ethyl acetate=30/70→0/100, ethyl acetate/methanol=100/0→95/5), and fractions
  15. additioncontaining the desired product
  16. concentrationwere concentrated under reduced pressure
  17. customThe obtained residue was purified by preparative HPLC, and fractions
  18. additioncontaining the desired product
  19. concentrationwere concentrated under reduced pressure
  20. additionA saturated aqueous sodium hydrogen carbonate solution (10 mL) was added to the obtained residue
  21. extractionthe mixture was extracted with ethyl acetate (15 mL)
  22. washThe organic layer was washed with saturated brine (5 mL)
  23. dry with materialdried over anhydrous sodium sulfate
  24. filtrationThe insoluble material was filtered off
  25. concentrationthe filtrate was concentrated under reduced pressure
  26. additionEthyl acetate and hexane were added to the obtained residue
  27. filtrationThe obtained precipitate was collected by filtration
  28. customdried

Sources & evidence

ORD record
ord-908215e4e17144828cee68f3c04a1040
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Reaction notes

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