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

HRID 509119Notes

Reaction equation

HRID 509119 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+].Br[CH2:44][C:45]1[CH:50]=[CH:49][C:48]([C:51]([F:54])([F:53])[F:52])=[CH:47][C:46]=1[C:55]1[CH:60]=[CH:59][N:58]=[N:57][CH:56]=1>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[CH2:44][C:45]1[CH:50]=[CH:49][C:48]([C:51]([F:53])([F:54])[F:52])=[CH:47][C:46]=1[C:55]1[CH:60]=[CH:59][N:58]=[N:57][CH:56]=1)#[N:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 666531564-[2-(Bromomethyl)-5-(trifluoromethyl)phenyl]pyridazineHCID 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 666527743-Cyano-N-(2,4-dimethoxybenzyl)-4-[2-pyridazin-4-yl-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, 100 mg, 0.19 mmol) in tetrahydrofuran (2 mL) was added a 2 M aqueous solution of potassium carbonate (270 μL, 0.54 mmol) and 4-[2-(bromomethyl)-5-(trifluoromethyl)phenyl]pyridazine (Preparation 33, 57 mg, 0.18 mmol). The solution was sparged with nitrogen before the addition of tetrakis(triphenylphosphine)palladium (0) (20.8 mg, 0.018 mmol). The reaction mixture was heated at 65° C. for 6 hours. The reaction mixture was cooled to ambient temperature and partitioned between a saturated aqueous solution of ammonium chloride (5 mL) and ethyl acetate (2×10 mL). A saturated aqueous solution of sodium chloride was added to aid the separation. The combined organic layer was dried over anhydrous magnesium sulphate, filtered and concentrated in vacuo to give a brown oil. The material was purified by silica gel column chromatography (ISCO™ companion, 12 g column, 0-30% ethyl acetate in heptane gradient elution). Fractions containing product were combined and concentrated in vacuo to obtain the title compound as a foam.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. custompartitioned between a saturated aqueous solution of ammonium chloride (5 mL) and ethyl acetate (2×10 mL)
  3. additionA saturated aqueous solution of sodium chloride was added
  4. customthe separation
  5. dry with materialThe combined organic layer was dried over anhydrous magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a brown oil
  9. customThe material was purified by silica gel column chromatography (ISCO™ companion, 12 g column, 0-30% ethyl acetate in heptane gradient elution)
  10. additionFractions containing product
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ec5af33526ed4aa19e9118a371662809
Source dataset
uspto-grants-2015_08
Patent number
US09096558B2

Reaction notes

Loading…