Structure of 16732-66-4
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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. : | 16732-66-4 |
Formula : | C6H7BrN2 |
M.W : | 187.04 |
SMILES Code : | NNC1=CC=CC=C1Br |
MDL No. : | MFCD00044518 |
InChI Key : | ZWMQVBSLMQSMDH-UHFFFAOYSA-N |
Pubchem ID : | 85583 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
* 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 |
---|---|---|
With hydrogenchloride; tin(ll) chloride; sodium nitrite; | The reaction of 3,6-di-tert-butyl-9H-carbazole with NBS produced 1-bromo-3,6-di-tert-butyl-9H-carbazole as a white-glassy solid in 80% yield after purification by flash chromatography on silica gel (FIG. 13). [0082] The unsubstituted carbazole derivative (3H-H) required use of 1-bromo-carbazole which was prepared according to the sequence shown in FIG. 14. 2-bromophenylhydrazine was added to a solution of cyclohexanone in glacial acetic acid to form 2-bromophenylhydrazone, which undergoes cyclization under reflux in the same solution, producing 1,2,3,4-tetrahydrocarbazole. Dehydrogenation of tetrahydrocarbazole is carried out with chloranil in boiling xylene, to give 1-bromo-carbazole (FIG. 14). The dehydrogenation may also be carried out with palladium on charcoal. [0083] These bromo-carbazoles were reacted with 2-pyridylzinc bromide in THF, using tetrakis(triphenylphosphine)palladium(0) as precatalyst, under Negishi coupling conditions the coupling product was formed in 85% yield (FIG. 15). For this coupling reaction it was necessary to protect the nitrogen in the carbazole fragment because of the susceptibility of aryl zinc compounds to protonolysis. This was done simply by deprotonating the carbazole nitrogen with KH and performing the coupling reaction on the potassium salt of the carbazole. [0084] Using examples of the ligands produced as described above, boron difluoride complexes wore prepared according to procedures described below. | |
General procedure: Substituted aniline 4a-4s (50 mmol) was dissolved in the 50 mL HCl (18%, aqueous) in the icebath. NaNO2 (50 mmol) dissolved in 50 mL water was added dropwise. The reaction mixture wasstirred for 1 h to obtain a clear solution. Then the solution of SnCl2 (0.1 mol) in 30 mL of concentratedHCl was added dropwise at 0 C. The mixture was stirred at room temperature for 2 h. Afterwards,the mixture was extracted with 50 mL EtOAc and the organic impurities were discarded. Then thesolution was basified with NaOH (40%, aqueous) until it reached pH 7.0. The reaction mass wasextracted with EtOAc three times. Finally, substituted phenylhydrzine 5a-5s was afforded after beingvapored under reduced pressure (in 55%-80% yield) [12]. | ||
(1)diazotization A 5L three-necked flask 200g2_ bromoaniline and 600ml37% concentrated hydrochloric acid, with ice-salt cooled to 2 C, was added with stirring 270g of 35% aqueous sodium nitrite solution, maintaining the temperature between 2 C for 1.5 hour.(2)reduction37% concentrated hydrochloric acid was added 730ml, 730ml of water and 195g of zinc powder to the reaction mixture, maintaining the temperature at 18 C until completion of the reaction between the reaction, the reaction solution changed to off-white, then add 25% sodium hydroxide solution to the reaction gas solution PH value of 10, 5 C incubated for 1.5 hours, and the precipitated crystals were filtered to give 117g2- bromophenylhydrazine crude. |
After 20.0 grams (g) (116 millimoles (mmol)) of 2-bromoaniline was dissolved in 100 milliliters (mL) of a 20% aqueous HCl solution, 15 mL (128 mmol) of an aqueous sodium nitrate solution was slowly added thereto at about 0 C. The reaction mixture was stirred for about 1 hour, followed by addition of a solution of 60 mL (116 mmol) of stannous chloride dihydrate dissolved in a 35% aqueous HCl solution. The reaction mixture was stirred at room temperature for about 2 hours. After completion of the reaction, a solid was filtered from the resulting reaction mixture, washed twice with a 35% aqueous HCl solution, and dried under reduced pressure, thereby obtaining about 16 g (85,8 mmol, Yield: 74%) of Intermediate 1-4 without performing a purification process. This compound was identified by liquid chromatography-mass spectrometry (LC-MS). After 20.0 grams (g) (116 millimoles (mmol)) of 2-bromoaniline was dissolved in 100 milliliters (mL) of a 20% aqueous HCl solution, 15 mL (128 mmol) of an aqueous sodium nitrate solution was slowly added thereto at about 0 C. The reaction mixture was stirred for about 1 hour, followed by addition of a solution of 60 mL (116 mmol) of stannous chloride dihydrate dissolved in a 35% aqueous HCl solution. The reaction mixture was stirred at room temperature for about 2 hours. After completion of the reaction, a solid was filtered from the resulting reaction mixture, washed twice with a 35% aqueous HCl solution, and dried under reduced pressure, thereby obtaining about 16 g (85,8 mmol, Yield: 74%) of Intermediate 1-4 without performing a purification process. This compound was identified by liquid chromatography-mass spectrometry (LC-MS). LC-MS m/z=186.98 (M+H)+ |