Chlorosulfamic acid → 2-Sulfamoylamino-6-(tetrahydrofuran-2-yl)benzonitrile

HRID 1467221Notes

Reaction equation

HRID 1467221 reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]2[O:11][CH2:12][CH2:13][CH:14]=2)[C:3]=1[C:4]#[N:5].C([O-])=O.[NH4+].[S:19](Cl)(=[O:22])(=[O:21])[NH2:20]>CO.[Pd]>[S:19]([NH:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]2[CH2:14][CH2:13][CH2:12][O:11]2)[C:3]=1[C:4]#[N:5])(=[O:22])(=[O:21])[NH2:20]

Participants

6

Reactant 3

HCID 24499Chlorosulfamic acidHCID 2723923Ammonium formateHCID 667461322-Amino-6-(4,5-dihydrofuran-2-yl)benzonitrile

Product 1

HCID 667461382-Sulfamoylamino-6-(tetrahydrofuran-2-yl)benzonitrileYield 17.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

2-Amino-6-(4,5-dihydrofuran-2-yl)benzonitrile (Example 186b) (0.24 g, 1.28 mmol), 10% Pd/C (0.24 g), and ammonium formate (2.40 g, 38.1 mmol) were refluxed in MeOH (25 mL) under nitrogen for 1.5 h. The insoluble solids were filtered out and discarded, and the solvent was removed under vacuum. The resultant residue was dissolved in EtOAc, washed with saturated Na2CO3 and brine, dried over MgSO4 and concentrated under vacuum. The residue was dissolved in anhydrous DMA (2.0 mL) and was treated with sulfamoyl chloride (0.11 g, 0.97 mmol). The reaction mixture was stirred under nitrogen for 30 minutes, quenched with water (5.0 mL) and extracted with EtOAc (3×50 mL). The combined extract was dried over MgSO4, filtered and concentrated under vacuum. The crude product was purified by silica gel prep-TLC using 65% EtOAc/hexanes to give 45.0 mg (13%) of the title compound as a white solid. 1H NMR (400 MHz, Acetone-d6) δ 1.71-1.78 (m, 1H), 2.02-2.07 (m, 2H), 2.45-2.52 (m, 1H), 3.90-3.95 (m, 1H), 4.10-4.15 (m, 1H), 5.08 (t, J=6.8 Hz, 1H), 6.6-6.8 (broad, 2H), 7.36-7.39 (m, 1H), 7.62-7.63 (m, 2H), 8.22 (broad s, 1H). MS 268 (MH+).

Workup

  1. filtrationThe insoluble solids were filtered out and
  2. customthe solvent was removed under vacuum
  3. dissolutionThe resultant residue was dissolved in EtOAc
  4. washwashed with saturated Na2CO3 and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under vacuum
  7. dissolutionThe residue was dissolved in anhydrous DMA (2.0 mL)
  8. customquenched with water (5.0 mL)
  9. extractionextracted with EtOAc (3×50 mL)
  10. extractionThe combined extract
  11. dry with materialwas dried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated under vacuum
  14. customThe crude product was purified by silica gel prep-TLC

Sources & evidence

ORD record
ord-be54bdd0d9ab4bfb8fbc7da20ff2121e
Source dataset
uspto-grants-2015_04
Patent number
US09000054B2

Reaction notes

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