Potassium Carbonate → 3-Cyano-N-(2,4-dimethoxybenzyl)-4-[2-methoxy-4-(trifluoromethyl)benzyl]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

HRID 509115Notes

Reaction equation

HRID 509115 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([S:17]([N:20]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][C:28]=2[O:35][CH3:36])[C:21]2[S:25][N:24]=[CH:23][N:22]=2)(=[O:19])=[O:18])[CH:6]=[CH:7][C:8]=1B1OCC(C)(C)CO1)#[N:2].C(=O)([O-])[O-].[K+].[K+].[CH3:43][O:44][C:45]1[CH:52]=[C:51]([C:53]([F:56])([F:55])[F:54])[CH:50]=[CH:49][C:46]=1[CH2:47]Br>O1CCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([C:3]1[CH:4]=[C:5]([S:17]([N:20]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][C:28]=2[O:35][CH3:36])[C:21]2[S:25][N:24]=[CH:23][N:22]=2)(=[O:18])=[O:19])[CH:6]=[CH:7][C:8]=1[CH2:47][C:46]1[CH:49]=[CH:50][C:51]([C:53]([F:54])([F:55])[F:56])=[CH:52][C:45]=1[O:44][CH3:43])#[N:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 36885692-Methoxy-4-(trifluoromethyl)benzyl bromideHCID 866824833-cyano-N-(2,4-dimethoxybenzyl)-4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

Product 1

HCID 866824793-Cyano-N-(2,4-dimethoxybenzyl)-4-[2-methoxy-4-(trifluoromethyl)benzyl]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 3-cyano-N-(2,4-dimethoxybenzyl)-4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide (Preparation 29, 45.5 mg, 0.086 mmol) in tetrahydrofuran (1 mL) was added a 2 M aqueous solution of potassium carbonate (116 μL, 3.03 mmol) and 2-methoxy-4-(trifluoromethyl)benzyl bromide (21 mg, 0.08 mmol). The solution was sparged with nitrogen before the addition of tetrakis(triphenylphosphine)palladium (0) (9.2 mg, 0.0008 mmol). The reaction mixture was heated at 65° C. for 6 hours. The reaction mixture was cooled to ambient temperature and partitioned between 1N aqueous citric acid solution (2 mL) and ethyl acetate (10 mL). The organic layer was washed with a saturated aqueous solution of sodium chloride (2 mL), dried over anhydrous magnesium sulphate, filtered and concentrated in vacuo to give a yellow oil. The material was purified by silica gel column chromatography (ISCO™ companion, 12 g column, 0-50% ethyl acetate in heptane gradient elution). Fractions containing product were combined and concentrated in vacuo to obtain the title compound as a yellow oil, which was used without further purification.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. custompartitioned between 1N aqueous citric acid solution (2 mL) and ethyl acetate (10 mL)
  3. washThe organic layer was washed with a saturated aqueous solution of sodium chloride (2 mL)
  4. dry with materialdried over anhydrous magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a yellow oil
  8. customThe material was purified by silica gel column chromatography (ISCO™ companion, 12 g column, 0-50% ethyl acetate in heptane gradient elution)
  9. additionFractions containing product
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-19a51076529d4ff4a0500c63dbb46fe9
Source dataset
uspto-grants-2015_08
Patent number
US09096558B2

Reaction notes

Loading…