Acetic Anhydride → HCID 136397117, compound

HRID 2110585Notes

Reaction equation

HRID 2110585 reaction equation
[NH2:1][C:2]1([CH2:34][CH2:35][CH:36]([CH3:38])[CH3:37])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([OH:12])=[C:4]([C:13]2[NH:18][C:17]3[CH:19]=[CH:20][C:21]([NH:23]C(=O)OC(C)(C)C)=[CH:22][C:16]=3[S:15](=[O:32])(=[O:31])[N:14]=2)[C:3]1=[O:33].C(N(CC)CC)C.[C:46]([O:49]C(=O)C)(=O)[CH3:47].[CH3:53][S:54](Cl)(=[O:56])=[O:55]>ClCCl>[OH:12][C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]([NH:1][C:46](=[O:49])[CH3:47])([CH2:34][CH2:35][CH:36]([CH3:37])[CH3:38])[C:3](=[O:33])[C:4]=1[C:13]1[NH:18][C:17]2[CH:19]=[CH:20][C:21]([NH:23][S:54]([CH3:53])(=[O:56])=[O:55])=[CH:22][C:16]=2[S:15](=[O:32])(=[O:31])[N:14]=1

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 8471Triethylamine2×HCID 31297Methanesulfonyl chlorideHCID 135885150HCID 135885150, compound

Product 1

HCID 136397117HCID 136397117, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of Example 18C (30 mg, 0.05 mmol) in dichloromethane (150 μL) was added triethylamine (150 μL, 0.11 mmol) and acetic anhydride (6 μL, 0.06 mmol) and the mixture stirred at room temperature for 16 hours. Solvent was removed in vacuo and the crude residue was dissolved in dichloromethane (0.5 mL) and trifluoroacetic acid (0.5 mL) and the mixture was stirred at room temperature for 2 hours. Solvent was removed in vacuo and the crude residue was dissolved in dichloromethane (0.5 mL) and triethylamine (150 μL, 0.11 mmol) was added followed by methanesulfonyl chloride (10 μL, 0.11 mmol). The mixture was stirred at room temperature for 1.5 hours and the solvent was removed in vacuo and the crude residue was dissolved in ethyl acetate (0.5 mL) and 1N NaOH (0.5 mL) and the solution stirred at room temperature for 16 hours. 1N HCl was added dropwise until acidic pH, then the mixture was extracted with ethyl acetate (3×5 mL) and the organic extracts were combined and dried (MgSO4). The drying agent was filtered off and the solvent was removed in vacuo to give a crude residue which was purified by column chromatography on silica gel (5% methanol/chloroform) to give the title compound as a colorless solid. MS (ESI) m/z 561 (M+H+). 1H NMR (d6-DMSO) δ 10.03 (s, 1H), 8.04, 8.02 (d, 1H), 7.55-7.25 (m, 6H), 3.07, 3.06 (d, 3H), 2.01-1.59 (m, 2H), 1.82 (s, 3H), 1.31-1.08 (m, 2H), 1.01-0.84 (m, 1H), 0.71-0.62 (m, 6H).

Workup

  1. customSolvent was removed in vacuo
  2. dissolutionthe crude residue was dissolved in dichloromethane (0.5 mL)
  3. stirringtrifluoroacetic acid (0.5 mL) and the mixture was stirred at room temperature for 2 hours
  4. customSolvent was removed in vacuo
  5. dissolutionthe crude residue was dissolved in dichloromethane (0.5 mL)
  6. stirringThe mixture was stirred at room temperature for 1.5 hours
  7. customthe solvent was removed in vacuo
  8. dissolutionthe crude residue was dissolved in ethyl acetate (0.5 mL)
  9. stirring1N NaOH (0.5 mL) and the solution stirred at room temperature for 16 hours
  10. addition1N HCl was added dropwise until acidic pH
  11. extractionthe mixture was extracted with ethyl acetate (3×5 mL)
  12. dry with materialdried (MgSO4)
  13. filtrationThe drying agent was filtered off
  14. customthe solvent was removed in vacuo
  15. customto give a crude residue which
  16. customwas purified by column chromatography on silica gel (5% methanol/chloroform)

Sources & evidence

ORD record
ord-401bfa828b604a91a5e198e3a8b659b0
Source dataset
uspto-grants-2009_04
Patent number
US07517876B2

Reaction notes

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