Pyridine → HCID 11669769, compound

HRID 1725943Notes

Reaction equation

HRID 1725943 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([NH:11][C:12]1[CH:21]=[CH:20][C:19]2[CH2:18][CH2:17][CH2:16][CH2:15][C:14]=2[C:13]=1[C:22]([OH:24])=[O:23])(=[O:10])=[O:9].Cl[CH2:26][C:27](Cl)=[O:28].[N:30]1[CH:35]=[CH:34]C=[CH:32][CH:31]=1.C(NCC)C>C(Cl)Cl.C(OCC)(=O)C>[CH2:31]([N:30]([CH2:35][CH3:34])[CH2:26][C:27]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([NH:11][C:12]1[CH:21]=[CH:20][C:19]2[CH2:18][CH2:17][CH2:16][CH2:15][C:14]=2[C:13]=1[C:22]([OH:24])=[O:23])(=[O:10])=[O:9])=[O:28])[CH3:32]

Participants

7

Reactant 4

HCID 1049PyridineHCID 6577Chloroacetyl chlorideHCID 8021DiethylamineHCID 11573782HCID 11573782, compound

Product 1

HCID 11669769HCID 11669769, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of Example 294 (0.0590 g, 0.17 mmol) in CH2Cl2 (3.0 mL) was treated with chloroacetyl chloride (16 μL, 0.20 mmol) and pyridine (69 μL, 0.85 mmol), stirred 4 hours at room temperature, then quenched with 1N HCl (10 mL). The layers were separated and the organic layer was washed with brine, dried (MgSO4), filtered, and concentrated to a residue (45.0 mg). The residue was dissolved in acetone (0.4 mL), treated with diethylamine (50 μL, 0.48 mmol), heated to 60° C. for 2 hours, cooled to room temperature, diluted with ethyl acetate (10 mL), and washed with 1N HCl (10 mL). The organic layer was dried (MgSO4), filtered and concentrated. The concentrate was purified by C18 reverse-phase HPLC using acetonitrile/water/0.1% TFA to provide the desired product (8.7 mg, 18%). MS (ESI(+)) m/e 460 (M+H)+; MS (ESI(−)) m/e 458 (M−H)−; 1H NMR (300 MHz, DMSO-d6) δ 7.79 (m, 2H), 7.56 (m, 1H), 7.23 (m, 2H), 6.90 (m, 1H), 3.30 (m, 4H), 2.80 (m, 2H), 2.73 (s, 2H), 2.59 (m, 2H), 1.61 (m, 4H), 1.06 (m, 6H).

Workup

  1. customquenched with 1N HCl (10 mL)
  2. customThe layers were separated
  3. washthe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated to a residue (45.0 mg)
  7. dissolutionThe residue was dissolved in acetone (0.4 mL)
  8. temperatureheated to 60° C. for 2 hours
  9. temperaturecooled to room temperature
  10. washwashed with 1N HCl (10 mL)
  11. dry with materialThe organic layer was dried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe concentrate was purified by C18 reverse-phase

Sources & evidence

ORD record
ord-7a09903f8e1144e3922d806bf385e007
Source dataset
uspto-grants-2009_02
Patent number
US07491718B2

Reaction notes

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