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Structure of 1235406-85-5

Chemical Structure| 1235406-85-5

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Product Details of [ 1235406-85-5 ]

CAS No. :1235406-85-5
Formula : C14H13ClF2N2O4S2
M.W : 410.84
SMILES Code : O=C(OC(C)(C)C)N(S(=O)(C1=CC(Cl)=C(F)C=C1F)=O)C2=CSC=N2
MDL No. :MFCD22575038

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Application In Synthesis of [ 1235406-85-5 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 1235406-85-5 ]

[ 1235406-85-5 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 1235406-42-4 ]
  • [ 13656-57-0 ]
  • [ 1235406-85-5 ]
YieldReaction ConditionsOperation in experiment
67% EXAMPLE 38 Synthesis of (S)-4-((1-benzylpyrrolidin-3-yl)(methyl)amino)-5-chloro-2-fluoro-//-(thiazol- 4-yl)benzenesulfonamide 2,2,2-trifluoroacetate Step 1. Preparation of terf-butyl ((5-chloro-2,4-difluorophenyl)sulfonyl)(thiazol-4- yl)carbamate To a solution of terf-butyl thiazol-4-ylcarbamate (160.0 g, 799.0 mmol) in anhydrous tetrahydrofuran (1500 mL) was added lithium bis(trimethylsilyl)amide (1 M solution in tetrahydron, 1120 mL) at -78 C. The reaction mixture was warmed to 5 C, stirred for 30 minutes, and cooled to -78 C. To it was then added dropwise a solution of 5-chloro-2,4-difluorobenzenesulfonyl chloride (355.3 g, 1440 mmol) in anhydrous tetrahydrofuran (500 mL) at -78 C. The reaction mixture was allowed to warm to ambient temperature and stirred for 12h. To it was then added saturated ammonium chloride (200 mL), and the mixture was extracted with ethyl acetate (3 chi 1000 mL). The combined organic phase was washed with brine (3 chi 1000 mL), dried over anhydrous sodium sulfate, and filtered. Concentration of the filtrate in vacuo and trituration of the residue with methanol (500 mL) provided the title compound as a colorless solid (220.0 g, 67% yield): H NMR (400MHz, DMSO-cfe) £9.14 (d, J = 2.2 Hz, 1 H), 8.25 (t, J = 7.6 Hz, 1 H), 8.06-7.94 (m, 2H), 1.28 (s, 9H); MS (ES+) m/z 310.8 (M - 99), 312.8 (M - 99).
31.8% Under N2 protection,Z-0-2 (8.0 g, 0.04 mol)Was dissolved in dry THF (80 ml)The mixture was cooled to -78 C,LiHMDS (IM, 48 ml, 0.048 mol)Of THF solution.After the dropwise addition,The mixture is in-78 C,Stir for 0.5 h.The reaction solution was slowly warmed to room temperature,Stir for 1h,Then cooled to -78 C,5-Chloro-2,4-difluorobenzenesulfonyl chloride (11.11 g, 0.048 mol)In THF (50 ml) was added dropwise to the above reaction solution.The mixture was stirred at -78 & lt; 0 &After stirring for 1 h, the temperature was raised to room temperature,And stirred at room temperature for 16 h.To the reaction solution was added saturated aqueous ammonium chloride solution (250 ml) and extracted with ethyl acetate (3 x 100 ml) to combine the organic phases,Washed with saturated brine (200 ml)dry,40 C spin dry.Crude column (100-200 mesh silica gel), eluent as petroleum ether: ethyl acetate = (4: 1),To give Z-0-3 (5.11 g, yield: 31.8%)As a white solid. ESI-MS (M + Na) +: 434.0, purity: 95.9% (UV214).
To a solution of thiazol-4-yl-carbamic acid te/t-butyl ester (Preparation 3, 503 mg, 2.51 mmol) in tetrahydrofuran (5.0 ml_) cooled to -78 C was added lithium hexamethyldisilazide (1 .0 M in tetrahydrofuran, 2.76 ml_, 2.76 mmol). The reaction mixture was stirred for 30 minutes at ambient temperature then cooled to -78 C. A sol ution of 5-chloro-2,4-difluorobenzenesulfonyl chloride (620.5 mg, 2.51 mmol) in tetrahydrofuran (5.0 ml_) was added slowly via a syringe. After the addition was complete, the reaction mixture was allowed to warm gradually to ambient temperature. After 24 hours, the reaction mixture was poured into saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo onto diatomaceous earth. The residue was purified by automated silica gel flash chromatography (0% to 5% ethyl acetate in dichloromethane gradient elution) to afford the title compound as a white solid (733 mg).1 HNMR (de-DMSO): delta 1 .40 (s, 9H), 7.10 (m, 1 H), 7.52 (m, 1 H), 8.25 (t, 1 H), 8.80 (m, 1 H).LCMS Rt = 1 .70 min MS m/z 31 1 [M(-Boc)H]+
[0169] To a solution of 40-2 (1.0 g, 4.9 mmol) in 20 mL of THE was added LiHMDS (5.8 mL, 5.8mmol) at -78 C, and the mixture was stirred for 1 h under N2at room temperature. After beingcooled back to -78 C, a solution of 19-4(1.1 g, 4.5 mmol) in 2 mL of THE was added to the above solution. Then the mixture was warmed to room temperature and stirred for 1 h. The reaction was quenched with NH4CI and extracted with EtOAc. The organic layer was washed with water and brine, dried over Mg504, filtered and concentrated. The crude product was purified bycolumn chromatography on silica gel (PE: EtOAc = 8:1) to give 7-1. ?H NMR (400 MHz CDCI3) S8.80 (d, J = 2.0 Hz, 1H), 8.23 (t, J = 7.6 Hz, 1H), 7.53 (d, J = 2.0 Hz, 1H), 7.09 (t, J = 8.4 Hz, 1H), 1.37 (s, 9H). MS m/z (Mi-H): 411
To a solution of 40-2 (1.0 g, 4.9 mmol) in 20 mL of THE was added LiHMDS (5.8 mL, 5.8 mmol) at -78 C, and the mixture was stirred for 1 h under N2at room temperature. After being cooled back to -78 C, a solution of 19-4 (1.1 g, 4.5 mmol) in 2 mL of THE was added to the above solution. Then the mixture was warmed to room temperature and stirred for 1 h. The reaction was quenched with NH4CI and extracted with EtOAc. The organic layer was washed with water and brine, dried over Mg504, filtered and concentrated. The crude product was purified by column chromatography on silica gel (PE: EtOAc = 8:1) to give 7-1. ?H NMR (400 MHz CDCl3) 5 8.80 (d, J = 2.0 Hz, 1H), 8.23 (t, J = 7.6 Hz, 1H), 7.53 (d, J = 2.0 Hz, 1H), 7.09 (t, J = 8.4 Hz, 1H), 1.37 (s, 9H). MS m/z (M+H): 411

  • 2
  • [ 1235406-85-5 ]
  • [ 152673-32-0 ]
  • tert-butyl (2S,4S)-4-((4-(N-(tert-butoxycarbonyl)-N-(thiazol-4-yl)sulfamoyl)-2-chloro-5-fluorophenyl)amino)-2-methylpyrrolidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
55% With triethylamine; In dimethyl sulfoxide; at 20.0℃; for 16.0h; EXAMPLE 231 Synthesis of 4-(((3S,5S)-1-benzyl-5-methylpyrrolidin-3-yl)(methyl)amino)-5-chloro-2- fluoro-Ay-(thiazol-4-yl)benzenesulfonamide formate Step 1. Preparation of te/f-butyl (2S,4S)-4-((4-(Ay-(te/f-butoxycarbonyl)-Ay-(thiazol-4- yl)sulfamoyl)-2-chloro-5-fluorophenyl)amino)-2-methylpyrrolidine-1-carboxylate To a solution of terf-butyl ((5-chloro-2,4-difluorophenyl)sulfonyl)(thiazol-4- yl)carbamate (1.71 g, 4.16 mmol) in anhydrous dimethyl sulfoxide (8 mL) was added te/f-butyl (2S,4S)-4-amino-2-methylpyrrolidine-1-carboxylate (1.00 g, 4.99 mmol) followed by triethylamine (0.70 mL, 4.99 mmol). The resulting solution was stirred at ambient temperature for 16 h. The crude reaction mixture was purified by column chromatography, eluting with 0 to 100% of ethyl acetate in heptane, to provide the title compound as a colorless solid (1.62 g, 55% yield).
  • 3
  • [ 1235406-85-5 ]
  • [ 171032-87-4 ]
  • (S)-5-chloro-2-fluoro-4-(1-(2-fluorophenyl)ethoxy)-N-(thiazol-4-yl)benzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
20% With caesium carbonate; In dimethyl sulfoxide; at 75℃; for 17h; To a solution of <strong>[171032-87-4](S)-1-(2-fluorophenyl)ethan-1-ol</strong> (0.102 g, 0.730 mmol) and tert-butyl ((5-chloro-2,4-difluorophenyl)sulfonyl)(thiazol-4-yl)carbamate (0.30 g, 0.730 mmol) in anhydrous dimethyl sulfoxide (3 mL) was added cesium carbonate (0.571 g, 1.75 mmol) and the reaction mixture was heated at 75 C. for 17 h. The reaction mixture was diluted with ethyl acetate (5 mL) and water (5 mL), and the aqueous phase was extracted with ethyl acetate (2×5 mL). The combined organic layers were washed with brine (5 mL), dried over anhydrous magnesium sulfate, and filtered. Concentration of the filtrate in vacuo and purification of the residue by preparative reverse phase HPLC using acetonitrile in water containing 0.1% of trifluoroacetic acid as eluent afforded the title compound as a colorless solid (0.062 g, 20% yield): 1H NMR (300 MHz, DMSO-d6) delta11.34 (s, 1H), 8.88 (d, J=2.2 Hz, 1H), 7.80 (d, J=7.5 Hz, 1H), 7.51-7.33 (m, 2H), 7.30-7.18 (m, 3H), 7.06 (d, J=2.2 Hz, 1H), 5.97 (q, J=6.4 Hz, 1H), 1.63 (d, J=6.4 Hz, 3H); MS (ES+) m/z 431.0 (M+1), 432.9 (M+1).
 

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