Structure of 50851-01-9
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 50851-01-9 |
Formula : | C14H12N2OS |
M.W : | 256.32 |
SMILES Code : | NC1=NC2=CC=C(OCC3=CC=CC=C3)C=C2S1 |
MDL No. : | MFCD09755107 |
InChI Key : | DBWISUPGDHAXIT-UHFFFAOYSA-N |
Pubchem ID : | 17244953 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
20% | With bromine; In formic acid; acetic acid; at -3 - 0℃;Inert atmosphere; Darkness; | General procedure: The synthesis of 6-ethoxy-1,3-benzothiazol-2-amine (1c), obtained following a general procedure for the preparation of aminobenzothiazoles described in the literature [13,14] is described. Aniline 6c (1.0 g, 7.36 mmol) and NH4SCN (1.6 g, 21.9 mmol) were dissolved in a 20% formic acid-glacial acetic acid mixture (100 mL) and cooled to-3 C with stirring, under N2. With the exclusion of light from the reaction mixture, bromine (0.30 mL dissolved in 20 mL of glacial acetic acid) was added dropwise, while the reaction temperature was kept between -3C and 0 C. The light shield was removed and the mixture was allowed to warm to room temperature overnight. Sodium hydroxide pellets and ice were added with stirring until pH 11 was attained, and the mixture was extracted with EtOAc. The organic layer was separated and filtered through celite to remove polythiocyanogen (SCN)n. The organic layer was then washed with water, saturated NaHCO3 and brine; then, the solvent was evaporated in vacuo. The residue was purified by flash chromatography (EtOAc/petroleum ether 1:1) to give 0.93 g (65%) of an orange solid: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In acetone; at 20℃;Cooling; | General procedure: 6-Alkoxy-2-aminobenzothiazoles (3a-m) (20 mmol) was dissolved in 30 mL acetone and 30 mmolof chloroacetyl chloride were added under cold conditions. The reaction was stirred for 9-10 h atroom temperature. Water was added to the reaction mixture after the solvent (acetone) was removedunder pressure-reducing conditions. The mixture was stirred for 0.5 h and filtered to yield a crudeproduct. It was then purified by silica gel column chromatography with dichloromethane to yield awhite solid 4a-m. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate; In acetone;Reflux; | General procedure: A mixture of compound 2 (2 g, 12 mmol), potassium carbonate (2 g, 14.4 mmol), appropriate alkylbromide or benzyl chloride derivatives (1.32 mmol), and a catalytic amount of benzyltriethylaminechloride (TEBA) in 50 mL acetone was heated under reflux for 18-24 h. After removing the solventunder reduced pressure, 80 mL of hot water was poured into the flask and the mixture was stirred for0.5 h to eliminate the excess of potassium carbonate. The remaining precipitate was filtered to yield arusset solid (3a-m), which was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: Sodium thiocyanate (0.37 g,4.5 mmol) was dissolved in MeOH (5 ml_) and cooled to 0 C. Bromine 190 mI_,3.69 mmol) was added slowly dropwise and the reaction stirred for 5 mins. 4-(2- fluorophenoxy)aniline (0.50 g,2.45 mmol) was added,and reaction mixture allowed to warm to r.t. and stirred for 18h. The solution was concentrated in vacuo,and the residue partitioned between DCM and sat. aq. NaHC03. The aqueous layer was extracted with DCM. The combined organics were dried (phase separator) and concentrated in vacuo. The residue was purified by chromatography (S1O2,0- 50% EtOAc in PE) to yield the title compound as a yellow solid (441 mg,69 %).1H NMR 6H (500 MHz,CDCI3) 7.51 (d,J = 8.8 Hz,1 H),7.23 (d,J = 2.5 Hz,1 H),7.22 - 7.18 (m,1 H),7.14 - 7.09 (m,2H),7.07 - 7.00 (m,2H),5.89 - 5.17 (br s,2H); LCMS: (Method A) 3.28 min,(261 .3,MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | With sodium hexamethyldisilazane; In tetrahydrofuran; at 20℃; for 3h; | To a mixture of Intermediate BL (50 mg,0.20 mmol) and Intermediate F (86 mg,0.29 mmol) in THF (2 mL) at r.t. was added sodium bis(trimethylsilyl)amide solution (2M in THF) (0.39 ml_,0.78 mmol). The mixture stirred for 3h,then quenched with water. The resultant suspension was filtered,and the solid washed (water),slurried (EtOH) and dried under vacuum to afford the title compound as an orange solid (21 mg,28 %). NMR dH(500 MHz,DMSO-d6) 12.21 (br s,1 H),1 1 .03 (br s,1 H),8.24 (s,1 H),7.73 (d,J = 2.5 Hz,1 H),7.71 (d,J = 8.9 Hz,1 H),7.61 (dd,J = 8.5,4.4 Hz,1 H),7.53 (d,J = 8.5 Hz,1 H),7.50 - 7.45 (m,2H),7.44 - 7.37 (m,2H),7.37 - 7.30 (m,1 H),7.15 (dd,J = 8.8,2.6 Hz,1 H),5.16 (s,2H); LCMS (Method A): 2.60 min,(378.1 MH+). |
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