Iodoethane → HCID 57422333, compound

HRID 548033Notes

Reaction equation

HRID 548033 reaction equation
[CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([CH2:7][NH:8][S:9]([C:12]2[CH:20]=[CH:19][C:15]([C:16]([OH:18])=[O:17])=[CH:14][CH:13]=2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:29](I)[CH3:30]>CN(C=O)C.C(OCC)(=O)C>[CH2:29]([N:8]([CH2:7][C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:22][CH:21]=1)[S:9]([C:12]1[CH:20]=[CH:19][C:15]([C:16]([OH:18])=[O:17])=[CH:14][CH:13]=1)(=[O:11])=[O:10])[CH3:30]

Participants

6

Reactant 3

HCID 6340IodoethaneHCID 10796Cesium carbonateHCID 454145104-{[(4-Methoxyphenyl)methyl]sulfamoyl}benzoic acid

Product 1

HCID 57422333HCID 57422333, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
165 °C

Procedure

4-(N-(4-methoxybenzyl)sulfamoyl)benzoic acid (Example 5-1b) (160 mg, 0.5 mmol) and Cesium Carbonate (325 mg, 1 mmol) were placed in a microwave vial and dissolved in 2 mL DMF. Ethyl iodide (155 mg, 1 mmol) was added into the reaction mixture. The reaction was placed in a microwave reactor and heated at 165° C. for 5 minutes. The reaction mixture was dissolved in Ethyl Acetate and washed with water. The organic layer was dried over sodium sulfate and evaporated under vacuum. The crude product was dissolved in 4/1 solution of 6N NaOH (aq)/tetrahydrofuran (3 mL) and stirred at ambient temperature for 6 hours. The solution was acidified with 3N HCl (aq) to a pH of ˜3 and the product was extracted with ethyl acetate (3×, 75 mL). The combined organic extracts were dried over sodium sulfate and concentrated under vacuum. The residue was taken up in methanol (3 mL) and purified by reverse phased HPLC (5-95% acetonitrile in H2O gradient:25 minutes). The compound was known to inhibit the hT2R14 with IC50 of 20 μM. Yield 35%. MS M+H calculated 350.11, found 350.0.

Workup

  1. customThe reaction was placed in a microwave reactor
  2. washwashed with water
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. customevaporated under vacuum
  5. dissolutionThe crude product was dissolved in 4/1 solution of 6N NaOH (aq)/tetrahydrofuran (3 mL)
  6. extractionthe product was extracted with ethyl acetate (3×, 75 mL)
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. concentrationconcentrated under vacuum
  9. custompurified by reverse
  10. customHPLC (5-95% acetonitrile in H2O gradient:25 minutes)

Sources & evidence

ORD record
ord-00a3eda476e94782a315e55b2c5f768d
Source dataset
uspto-grants-2011_05
Patent number
US07939671B2

Reaction notes

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