Water → HCID 57732274, Verbindung

HRID 401751Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 401751
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

Komponenten

9

Edukt 5

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

Produkt 1

HCID 57732274HCID 57732274, VerbindungAusbeute 21,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 178521658HCID 178521658, VerbindungKatalysatorHCID 313Hydrochloric AcidLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

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%).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-196968bcf6ba4200a03b87cf06a3ae3e
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08741934B2

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