Acetic Anhydride → HCID 59455976, compound

HRID 1808640Notes

Reaction equation

HRID 1808640 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([CH2:9][N:10]2[C:18]3[C:13](=[C:14]([CH2:19][OH:20])[CH:15]=[CH:16][CH:17]=3)[C:12]([N:21](S(C3SC(Cl)=CC=3)(=O)=O)[S:22]([C:25]3[S:26][C:27]([Cl:30])=[CH:28][CH:29]=3)(=[O:24])=[O:23])=[N:11]2)[CH:6]=[CH:7][CH:8]=1.C(N(CC)CC)C.[C:47](OC(=O)C)(=[O:49])[CH3:48].[OH-].[Na+]>ClCCl.CO>[Cl:30][C:27]1[S:26][C:25]([S:22]([NH:21][C:12]2[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][C:14]=3[CH2:19][OH:20])[N:10]([CH2:9][C:5]3[CH:4]=[C:3]([CH2:2][NH:1][C:47](=[O:49])[CH3:48])[CH:8]=[CH:7][CH:6]=3)[N:11]=2)(=[O:23])=[O:24])=[CH:29][CH:28]=1

Participants

7

Reactant 4

HCID 7918Acetic Anhydride2×HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 58054473HCID 58054473, compound

Product 1

HCID 59455976HCID 59455976, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

N-[1-{[3-(Aminomethyl)phenyl]methyl}-4-(hydroxymethyl)-1H-indazol-3-yl]-5-chloro-N-[(5-chloro-2-thienyl)sulfonyl]-2-thiophenesulfonamide (for a preparation see Intermediate 72) (53 mg, 0.082 mmol) was suspended in dichloromethane (0.5 mL) and triethylamine (0.115 mL, 0.823 mmol). Acetic anhydride (0.008 mL, 0.09 mmol) was added to the suspension and it stirred for 1 h. LCMS showed starting material remaining so dichloromethane (0.3 mL) and acetic anhydride (3.88 μL, 0.041 mmol) were added to the solution and stirred for 2 h. LCMS showed only a small amount of starting material remaining so the reaction mixture was concentrated in vacuo to leave an off-white residue, which was dissolved in methanol (3 mL) and treated with NaOH (1.546 mL, 3.09 mmol). The reaction was stirred at room temperature for 1 h and then was concentrated in vacuo, and acidified with 5% citric acid. The solution was extracted with ethyl acetate and the organic layer was washed twice with water (25 mL) and once with brine (25 mL). The organic layer was dried over anhydrous magnesium sulfate before being evaporated in vacuo. The yellow residue was dissolved in 1:1 MeOH-DMSO (1 mL) and purified by Mass Directed AutoPrep on Sunfire C18 column using Acetonitrile Water with a Formic acid modifier (Method A). The solvent was evaporated in vacuo to give the title compound (17 mg, 43%) as a colourless glassy solid. LCMS (System A) RT=0.91 min, ES+ve m/z 505/507 (M+H)+.

Workup

  1. additionwere added to the solution
  2. stirringstirred for 2 h
  3. concentrationwas concentrated in vacuo
  4. customto leave an off-white residue, which
  5. stirringThe reaction was stirred at room temperature for 1 h
  6. concentrationwas concentrated in vacuo
  7. extractionThe solution was extracted with ethyl acetate
  8. washthe organic layer was washed twice with water (25 mL) and once with brine (25 mL)
  9. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  10. custombefore being evaporated in vacuo
  11. dissolutionThe yellow residue was dissolved in 1:1 MeOH-DMSO (1 mL)
  12. custompurified by Mass Directed AutoPrep on Sunfire C18 column
  13. customThe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-caf5991a50cf4327a6b8c10156ac2df7
Source dataset
uspto-grants-2013_01
Patent number
US08357716B2

Reaction notes

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