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Structure of 658-27-5
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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. : | 658-27-5 |
Formula : | C6H7FN2 |
M.W : | 126.13 |
SMILES Code : | NNC1=CC=CC(F)=C1 |
MDL No. : | MFCD00041261 |
InChI Key : | HFSXFDKOXKNGIA-UHFFFAOYSA-N |
Pubchem ID : | 581026 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H301-H315-H318-H335 |
Precautionary Statements: | P280-P301+P310+P330-P302+P352-P305+P351+P338+P310 |
Class: | 6.1 |
UN#: | 2811 |
Packing Group: | Ⅲ |
* 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 |
---|---|---|
74.81% | General procedure: Substituted aniline (0.17mol) and aqueous solution of NaNO2 (71.0mL, 1.24mol) were successively added to aqueous hydrochloric acid (115mL) maintaining the temperature between 0 and 5C. The reaction mixture was stirred for 2h, alkalized to pH 6-7 with 12% w/v sodium carbonate solution, and the resulting diazonium salt solution was added drop-wise to sodium sulfite solution (443.0mL, 1.9mol) below 0C. And then the mixture was stirred at room temperature for a future 1h, concentrated hydrochloric acid (277.0mL) was added slowly, and heated to 100C for 3h. The mixture was then cooled and filtered, and dried to give compounds 12a-e. | |
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]. | ||
22.1 g | A process for the preparation of 3-fluorophenylhydrazine hydrochloride, comprising the steps of: [0019] diazotization [0020] was added in a 1 L three-necked flask 50 g of 3-fluoroaniline and 150 ml of 37% concentrated hydrochloric acid, Cool with ice salt to 2 C 35% aqueous sodium nitrite solution was added with stirring, The temperature was maintained at 2 C for 1 hour.reduction [0022] To the reaction solution was added 37 ml of concentrated hydrochloric acid (450 ml), 450 ml of water and 120 g of zinc powder, and the temperature was maintained at 18 C To complete reaction, the reaction solution becomes gray and then add 20% sodium hydroxide solution to the reaction solution PH value of 10,5 C insulation 1 Hour, precipitation of crystals, filter was 26. 6g 3-fluorophenylhydrazine crude. [0023] purification [0024] A crude product of 26. 6 g of 3-fluorophenylhydrazine was dissolved in 532 g of water, heated to 60 C to completely dissolve, and then Charcoal decolorization for 20 minutes, hot and filtered to a colorless filtrate, 5 C insulation for 1 hour, precipitation of crystals, filtration was 22. lg 3 - fluorophenylhydrazine Pure. |
292 g | (1) Diazotization: 10 g of a three-necked flask was added with 500 g of 3-fluoroaniline and 1500 ml of 37% concentrated hydrochloric acid, cooled with ice salt to 2 C, and 857 g of 35% aqueous solution of sodium nitrite was added with stirring. The temperature was maintained at 0 to 5 C for 1.5 hours. (2) Reduction: To the reaction solution was added 730 ml of 37% concentrated hydrochloric acid, 730 ml of water and 480 g of zinc powder, the reaction was maintained at a temperature between 18 C and the reaction was completed. The reaction liquid becomes off-white. Then 30% sodium hydroxide solution was added to the reaction solution to adjuste the pH value of 10.5 for 2 hours, crystals were precipitated and filtered to obtain crude 292 g 3-fluorophenylhydrazine. (3) Purification: A crude product of 292 g of 3-fluorophenylhydrazine was dissolved in 5840 g of water, heated to 60 C to completely dissolve, then right amount of activated carbon was added, decolorized for 20 minutes, hot-filtered at 5C for 2 hours to a colorless filtrate, crystallized, and filtered to give 236 g of pure 3-fluorophenylhydrazine. (4) Salt: A pure product of 236 g of 3-fluorophenylhydrazine was dissolved in 408 ml of 40% sulfuric acid, crystals were precipitated by stirring at 65 C to the reaction solution, cooled to 20 C, filtered, the filter cake was washed with acetone and dried to obtain 3-fluorophenylhydrazine sulfate finished product 379 g, Content of 99.3%,Yield 42.7%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | 2,6-di-tert-butyl-4-methylpyridine; In toluene; for 36h;Heating / reflux; | EXAMPLE 78 Preparation of 2-(3-Fluorophenyl)-6-methyl-1,2,5,6-tetrahydro-1,2,5,6,7-pentaza-as-indacene-3,4-dione A suspension of ethyl 4-chloro-1-methyl-6-trifluoromethanesulfonyloxy-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (524 mg, 2.05 mmol) in toluene is treated with <strong>[658-27-5]3-fluorophenyl hydrazine</strong> (651 mg, 5.13 mmol) and a catalytic amount of 2,6-di-t-butyl-4-methylpyridine, heated at reflux temperature for 36 h, cooled to room temperature and filtered.The filtercake is washed with cold toluene and dried in vacuo to give the 4-hydrazinyl intermediate as a white powder, 624 mg (88% yield).This white powder (550 mg, 1.59 mmol) is suspended in THF, treated with NaH (60% in oil, 187 mg, 5.58 mmol), heated at reflux temperature for 24 h, cooled to room temperature, quenched carefully with 10% HCl, diluted with EtOAc and filtered.The filtercake is washed sequentially with water and EtOAc and air-dried to afford the title product as a white powder, 391 mg (83% yield, 73% yield over 2 steps), identified by HNMR and mass spectral analyses. |