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Chemical Structure| 1254036-94-6 Chemical Structure| 1254036-94-6

Structure of 1254036-94-6

Chemical Structure| 1254036-94-6

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Product Details of [ 1254036-94-6 ]

CAS No. :1254036-94-6
Formula : C13H8ClIN2O2S
M.W : 418.64
SMILES Code : O=S(N1N=CC2=C1C=C(Cl)C=C2I)(C3=CC=CC=C3)=O

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Application In Synthesis of [ 1254036-94-6 ]

* 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 [ 1254036-94-6 ]

[ 1254036-94-6 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 1254036-94-6 ]
  • [ 118994-89-1 ]
  • [ 1254036-81-1 ]
YieldReaction ConditionsOperation in experiment
Method DAll weights, volumes and equivalents are relative to 6-chloro-4-iodo-1-(phenylsulfonyl)-1 H- indazole.Zinc chloride (3.6 eq, 1.17 wt, 52.7 g) in tetrahydrofuran (5 vols, 225 ml) is cooled to 0 to 5 C. A solution of the <strong>[118994-89-1]ethyl oxazole-5-carboxylate</strong> (1.1 eq, 0.37 wt, 18.1 g, corrected for 92 wt% assay) in tetrahydrofuran (5 vols, 225 ml) is added to the vessel. The suspension is cooled to -10 C (+/-5 C) under a nitrogen atmosphere and a 1 M solution of bis- (trimethylsilyl)-lithiumamide in tetrahydrofuran (1.80 eq, 4.30 vols, 193 ml) is added over 15 minutes maintaining the temperature at -10 C (+/-5 C). The resulting solution is stirred under a nitrogen atmosphere at -10 C (+/-5 C) for 1 hour. To the solution is added 6-chloro-4-iodo-1-(phenylsulfonyl)-1 H-indazole (1.0 eq, 1.0 wt, 45.0 g) and tetrakis triphenylphosphine palladium (0.03 eq, 0.083 wt, 3.73 g) (the mixture is degassed with vacuum/nitrogen 3 times) and then heated to 60C (+/-3C) for at least 6 hours. The reaction is then checked by HPLC for completion. The reaction solution is cooled to 0 C (+/-3 C) and a solution of 25% w/w diisobutylaluminium hydride in toluene (4.0 eq, 6.4 vols, 288 ml) is added maintaining the temperature at <5C. The resulting reaction solution is then stirred at 0C (+/-3C) for at least 1 hour. The reaction is then checked by HPLC (generic) for completion. The reaction mixture is added portion wise to a solution of citric acid (4.0 eq, 2.0 wt, 90 g) in water (10 vols, 450 ml) at 0 C (+/-5 C) over ~1 h. The resulting solution is stirred at 20 C for 15 minutes, extracted with ethyl acetate (10 vols, 450 ml), the organic layer is washed with water (2 x 3 vols, 2 x 135 ml) and filtered through a porosity 4 sinter. The organic layer is then evaporated under reduced pressure (45 C, 100 mbar) to 2 to 3 volumes, dimethyl sulphoxide (10 vols, 450 ml) is added and the solution evaporated under reduced pressure (45 C, 50 mbar) to remove all traces of other solvents. To the solution at 45 C is added water (5 vols, 225 ml) dropwise over 30 minutes, the resulting reaction mixture is cooled to 20 C over 3hr and stirred at 20 C for at least 15 hrs. The product is filtered, washed with a solution of dimethylsulphoxide:water (1 :2) (2 vols, 90 ml), then washed with water (3 vols, 135 ml), then dried under high vacuum at 60 C (+/-3 C) to constant probe temperature to afford (2-(6-chloro-1- (phenylsulfonyl)-1 H-indazol-4-yl)oxazol-5-yl)methanol as a beige solid.
  • 2
  • [ 1254036-94-6 ]
  • [ 118994-89-1 ]
  • [ 1254036-83-3 ]
YieldReaction ConditionsOperation in experiment
All weights, volumes and equivalents are relative to 6-chloro-4-iodo-1-(phenylsulfonyl)-1H-indazole.Zinc chloride (3.6 eq, 1.17 wt, 52.7 g) in tetrahydrofuran (5 vols, 225 ml) is cooled to 0 to 5 C. A solution of the <strong>[118994-89-1]ethyl oxazole-5-carboxylate</strong> (1.1 eq, 0.37 wt, 18.1 g, corrected for 92 wt % assay) in tetrahydrofuran (5 vols, 225 ml) is added to the vessel. The suspension is cooled to -10 C. (+/-5 C.) under a nitrogen atmosphere and a 1M solution of bis-(trimethylsilyl)-lithiumamide in tetrahydrofuran (1.80 eq, 4.30 vols, 193 ml) is added over 15 minutes maintaining the temperature at -10 C. (+/-5 C.). The resulting solution is stirred under a nitrogen atmosphere at -10 C. (+/-5 C.) for 1 hour. To the solution is added 6-chloro-4-iodo-1-(phenylsulfonyl)-1H-indazole (1.0 eq, 1.0 wt, 45.0 g) and tetrakis triphenylphosphine palladium (0.03 eq, 0.083 wt, 3.73 g) (the mixture is degassed with vacuum/nitrogen 3 times) and then heated to 60 C. (+/-3 C.) for at least 6 hours. The reaction is then checked by HPLC for completion. The reaction solution is cooled to 0 C. (+/-3 C.) and a solution of 25% w/w diisobutylaluminium hydride in toluene (4.0 eq, 6.4 vols, 288 ml) is added maintaining the temperature at . The resulting reaction solution is then stirred at 0 C. (+/-3 C.) for at least 1 hour. The reaction is then checked by HPLC (generic) for completion. The reaction mixture is added portion wise to a solution of citric acid (4.0 eq, 2.0 wt, 90 g) in water (10 vols, 450 ml) at 0 C. (+/-5 C.) over 1 h. The resulting solution is stirred at 20 C. for 15 minutes, extracted with ethyl acetate (10 vols, 450 ml), the organic layer is washed with water (2×3 vols, 2×135 ml) and filtered through a porosity 4 sinter. The organic layer is then evaporated under reduced pressure (45 C., 100 mbar) to 2 to 3 volumes, dimethyl sulphoxide (10 vols, 450 ml) is added and the solution evaporated under reduced pressure (45 C., 50 mbar) to remove all traces of other solvents. To the solution at 45 C. is added water (5 vols, 225 ml) dropwise over 30 minutes, the resulting reaction mixture is cooled to 20 C. over 3 hr and stirred at 20 C. for at least 15 hrs. The product is filtered, washed with a solution of dimethylsulphoxide:water (1:2) (2 vols, 90 ml), then washed with water (3 vols, 135 ml), then dried under high vacuum at 60 C. (±3 C.) to constant probe temperature to afford (2-(6-chloro-1-(phenylsulfonyl)-1H-indazol-4-yl)oxazol-5-yl)methanol as a beige solid.
All weights, volumes and equivalents are relative to6-chioro-4-iodo-1 -(phenylsulfonyl)-1 H-indazole.Zinc chloride (3.6 eq, 1.17 wt, 52.7 g) intetrahydrofuran (5 vols, 225 ml) is cooled to 0 to 5 C. A solution of the <strong>[118994-89-1]ethyl oxazole-5-carboxylate</strong> (1.1 eq, 0.37 wt, 18.1 g, corrected for92 wt % assay) in tetrahydroffiran (5 vols, 225 ml) is added tothe vessel. The suspension is cooled to -10 C. (+1-5 C.) under a nitrogen atmosphere and a 1M solution of bis-(trimethylsilyl)-lithiumamide in tetrahydrofuran (1.80 eq, 4.30vols, 193 ml) is added over 15 minutes maintaining the temperature at - 10C. (+ 1-5C.). The resulting solution is stirredunder a nitrogen atmosphere at -10 C. (+1-5 C.) for 1 hour. To the solution is added 6-chioro-4-iodo-1 -(phenylsulfonyl)1H-indazole (1.0 eq, 1.0 wt, 45.0 g) and tetrakis triphenylphosphine palladium (0.03 eq, 0.083 wt, 3.73 g) (themixture is degassed with vacuumlnitrogen 3 times) and then heated to 60 C. (+ 1-3 C.) for at least 6 hours. The reactionis then checked by HPLC for completion. The reaction solution is cooled to 0 C. (+1-3 C.) and a solution of 25% wlwdiisobutylaluminium hydride in toluene (4.0 eq, 6.4 vols, 288ml) is added maintaining the temperature at <5 C. The resulting reaction solution is then stirred at 0 C. (+1-3 C.) for atleast 1 hout The reaction is then checked by HPLC (generic) for completion. The reaction mixture is added portion wise toa solution of citric acid (4.0 eq, 2.0 wt, 90 g) in water (10 vols, 450 ml) at 0 C. (+1-5 C.) over 1 h. The resulting solutionis stirred at 20 C. for 15 minutes, extracted with ethyl acetate (10 vols, 450 ml), the organic layer is washed with water (2x3vols, 2x135 ml) and filtered through a porosity 4 sintet The organic layer is then evaporated under reduced pressure (45C., 100 mbar) to 2 to 3 volumes, dimethyl sulphoxide (10 vols, 450 ml) is added and the solution evaporated under reduced pressure (45 C., 50 mbar) to remove all traces ofother solvents. To the solution at 45 C. is added water (5 vols,225 ml) dropwise over 30 minutes, the resulting reactionmixture is cooled to 20 C. over 3 hr and stirred at 20 C. for at least 15 hrs. The product is filtered, washed with a solution of dimethylsulphoxide:water (1:2) (2 vols, 90 ml), thenwashed with water (3 vols, 135 ml), then dried under highvacuum at 60 C. (±3 C.) to constant probe temperature toafford (2-(6-chloro- 1 -(phenylsulfonyl)- 1 H-indazol-4-yl)ox- azol-5-yl)methanol as a beige solid.
 

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