Water → N-(3,3-dimethylbutyl)-4-[(1,3-thiazol-2-ylamino)sulfonyl]benzamide

HRID 1808171Notes

Reaction equation

HRID 1808171 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[S:13][CH:14]=[CH:15][N:16]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH3:17][C:18]([CH3:23])([CH3:22])[CH2:19][CH2:20][NH2:21].[C:24](=O)([O-])[O-:25].[Na+].[Na+].O.C(=O)([O-])[O-]>Cl.C(=[Mo](=C=O)(=C=O)(=C=O)(=C=O)=C=O)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:17][C:18]([CH3:23])([CH3:22])[CH2:19][CH2:20][NH:21][C:24](=[O:25])[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[S:13][CH:14]=[CH:15][N:16]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 962WaterHCID 10340Sodium CarbonateHCID 19660Carbonate IonHCID 197093,3-DimethylbutylamineHCID 10193184-Iodo-N-(thiazol-2-yl)benzenesulfonamide

Product 1

HCID 57732274N-(3,3-dimethylbutyl)-4-[(1,3-thiazol-2-ylamino)sulfonyl]benzamideYield 21.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 178521658HCID 178521658, compoundCatalystHCID 313Hydrochloric AcidSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 4-iodo-N-1,3-thiazol-2-yl-benzenesulfonamide (Preparation 98, 0.2 g, 0.5 mmol), 3,3-dimethylbutylamine (0.25 g, 2.5 mmol), hexacarbonylmolybdenum (70 mg, 0.2 mmol), palladium (II) acetate (6 mg, 0.02 mmol), and sodium carbonate (200 mg, 2 mmol) in water (1.5 mL, 83 mmol) was heated 30 min at 110° C. in the microwave. The reaction mixture was diluted with 1 N HCl and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in methylene chloride/methanol and MP-Carbonate (2.73 mmol/g loading; 0.9 g, 2.500 mmol) was added. After stirring 1 h, LC/MS analysis indicated complete capture of the target compound. The resin was washed with methylene chloride then stirred in 8:1 methylene chloride/acetic acid. LC/MS analysis indicated the target compound was released from the resin (not quantified). The mixture was filtered. The filtrate was concentrated in vacuo, and the residue was lyophilized from water/acetonitrile. The resulting solid was triturated with methylene chloride and ether. The resulting solid was purified on the Gilson (Semi-prep: Phenomenex 100×21.2 mm 10 micron C18 column. 20 mL/min. Gradient 15% B to 100% B over 25 min. Solvent A: 7800 water/200 acetonitrile/8 TFA. Solvent B: 7200 acetonitrile/800 water/8 TFA) to afford the title compound (39 mg, 20%).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in methylene chloride/methanol
  7. washThe resin was washed with methylene chloride
  8. stirringthen stirred in 8:1 methylene chloride/acetic acid
  9. filtrationThe mixture was filtered
  10. concentrationThe filtrate was concentrated in vacuo
  11. customThe resulting solid was triturated with methylene chloride and ether
  12. customThe resulting solid was purified on the Gilson (Semi-prep: Phenomenex 100×21.2 mm 10 micron C18 column. 20 mL/min. Gradient 15% B to 100% B over 25 min. Solvent A: 7800 water/200 acetonitrile/8 TFA. Solvent B: 7200 acetonitrile/800 water/8 TFA)

Sources & evidence

ORD record
ord-b7a38e6c693a46e7835430800536b82d
Source dataset
uspto-grants-2013_01
Patent number
US08357711B2

Reaction notes

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