Pyridine → HCID 117926238, compound

HRID 590624Notes

Reaction equation

HRID 590624 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([S:24]([C:27]3[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=3)(=[O:26])=[O:25])[C:9]([C:11]3[CH2:12][CH2:13][N:14]([C:17](OC(C)(C)C)=[O:18])[CH2:15][CH:16]=3)=[CH:10][C:3]=12.[N:34]1[CH:39]=CC=C[CH:35]=1.C1C([N+]([O-])=O)=CC=C([Cl-]C([O-])=O)C=1.Cl.CNC>C(Cl)Cl.FC(F)(F)C(O)=O.CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([S:24]([C:27]3[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=3)(=[O:26])=[O:25])[C:9]([C:11]3[CH2:12][CH2:13][N:14]([C:17]([N:34]([CH3:39])[CH3:35])=[O:18])[CH2:15][CH:16]=3)=[CH:10][C:3]=12

Participants

7

Reactant 3

HCID 1049PyridineHCID 10473Dimethylamine, hydrochlorideHCID 90408880HCID 90408880, compound

Product 1

HCID 117926238HCID 117926238, compoundYield 53%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 6422Trifluoroacetic acidSolvent

Procedure

Intermediate P-5-I (2 g, 6.94 mmol) was dissolved in CH2Cl2 (20 mL), to which trifluoroacetic acid (10 mL, excess) was added at 0° C. and the reaction mixture was stirred at room temperature for 2 h. Solvents were removed under reduced pressure and saturated NaHCO3 solution (50 mL) was added to it. Extraction was carried out using EtOAc (30 mL×2); the combined organic layers were washed with water (60 mL), brine (60 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to provide corresponding Boc-deprotected intermediate (1.6 g). It (0.5 g, 1.28 mmol) was dissolved in CH2Cl2 (10 mL) and cooled to 0° C. To this was added pyridine (1.0 mL, 12.8 mmol) and 4-nitrophenylchloroformate (1.29 g, 6.44 mmol) sequentially. The reaction mixture was stirred at room temperature for 3 h before solvent was removed under reduced pressure. To the residue obtained was added DMF (10 mL) and cooled to 0° C. To this reaction mixture, TEA (1.6 mL, 12.8 mmol) and dimethylaminehydrochloride (0.525 g, 6.44 mmol) were added and it was stirred at room temperature for 16 h. It was then diluted using water (30 mL) and extraction was carried out using EtOAc (20 mL×3). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified using silica gel column chromatography (25% acetone in hexane) to provide the title compound P-5-II (0.25 g, 53% yield). LCMS: m/z; 459.2 (M+1)+.

Workup

  1. additionwas added at 0° C.
  2. customSolvents were removed under reduced pressure and saturated NaHCO3 solution (50 mL)
  3. additionwas added to it
  4. extractionExtraction
  5. washthe combined organic layers were washed with water (60 mL), brine (60 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto provide corresponding Boc-deprotected intermediate (1.6 g)
  10. temperaturecooled to 0° C
  11. stirringThe reaction mixture was stirred at room temperature for 3 h before solvent
  12. customwas removed under reduced pressure
  13. customTo the residue obtained
  14. temperaturecooled to 0° C
  15. stirringit was stirred at room temperature for 16 h
  16. additionIt was then diluted
  17. extractionwater (30 mL) and extraction
  18. washThe combined organic layers were washed with brine (50 mL)
  19. dry with materialdried over anhydrous Na2SO4
  20. filtrationfiltered
  21. concentrationconcentrated under reduced pressure
  22. customThe residue was purified

Sources & evidence

ORD record
ord-b071ec3528cb429294b17678cf585a88
Source dataset
uspto-grants-2016_01
Patent number
US09233983B2

Reaction notes

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