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CAS No. : | 51516-70-2 | MDL No. : | MFCD00102729 |
Formula : | C10H7FN4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | SZEJYPAPBGNEMH-UHFFFAOYSA-N |
M.W : | 202.19 | Pubchem ID : | 688685 |
Synonyms : |
|
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
61% | In ethanol; for 2h;Reflux; | General procedure: A mixture of the appropriate phenylhydrazine (0.001 mol)and 10 mL of ethanol was stirred and allowed to reflux.Then, 2-(ethoxymethylene)malononitrile (0.001 mol) dissolvedin 10 mL of ethanol was slowly added. The reactionmixture was refluxed for 2 h. The reaction mixture waspoured into 50 mL of ice-cold water. The precipitate wascollected by filtration and washed with water to provide10a-c in 61-80% yield.5-amino-1-(4-fluorophenyl)-1H-pyrazole-4-carbonitrile (10a)Yield: 61%. MP: 173-174 C. IR (cm-1): 3297-3183; 2225;1662; 1568; 1222. 1H NMR (400 MHz, DMSO-d6, TMS, deltain p.p.m.): 7.31-7.25; (m; 2 H; H3?, H5?); 7.54-7.49; (m;2H; H2?, H6?); 7.67; (s; 1 H; H3). 13C NMR (100 MHz,DMSO-d6, TMS, delta in ppm): 73.2 (C4); 114.8 (CN); 116.3(d; J = 22.8 Hz; C3?, C5?); 126.9 (d; J = 8.9 Hz; C2?, C6?);133.7 (d; J = 2.8 Hz; C1?) 141.7 (C5); 151.4 (C3); 161.2 (d;J = 243.6 Hz; C4?). 19F NMR (376 MHz, DMSO-d6, TMS, deltain p.p.m.): -114.26. EI [M + 1]+ 203.07. |
61% | In ethanol; for 2h;Reflux; | General procedure: A mixture of the appropriate phenylhydrazine (0.001 mol) and10 mL of ethanol was stirred and allowed to reflux. Then, 2-(ethoxymethylene)malononitrile (0.001 mol) dissolved in 10 mL of ethanol was slowly added. The reaction mixture was refluxed for 2 h. The reaction mixture was poured into 50 mL of ice-cold water. The precipitate was collected by filtration and washed with water to produce 7-12 in 48-90% yield. |
In ethanol; for 3h;Reflux; | General procedure: A stirred mixture of para-substituted phenylhydrazine hydrochloride (0.025 mol) was dissolved inH2O (30 mL), then the pH of the mixture was adjusted to pH 7-8 by the dropwise addition of 10% NaOHsolution to form the free para-substituted phenyl hydrazines, which were then refluxed for 3 h withethoxymethylene malononitrile in an ethanol medium. After completion of the reaction, the reactionmixture was allowed to cool at room temperature, and the solid 2a-2d were filtered under vacuum. Thecrude products obtained were recrystallized from DMF to afford the pure products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With sodium ethanolate; sodium hydride; In ethanol; at 20℃; for 2h;Heating / reflux; | Sodium hydride as a 60% dispersion in mineral oil (5.90 g, 1.2 eq, 0.147 mol.) was added slowly to ethanol (200 ml) at room temperature. To the solution of sodium ethoxide in ethanol was added 4-fluorophenylhydrazine hydrochloride (23.96 g, 1.2 eq, 0.147 mol.), addition of ethoxymethylene malonitrile (15.00 g, 1.0 eq, 0.123 mol.) shortly followed. The reaction mixture was heated to reflux with stirring for 2 hours. The reaction was then allowed to cool to room temperature, once at room temperature diethyl ether (50 ml) was added to the reaction mixture. The resultant precipitate was collected by filtration, washed with diethyl ether (2 x 100 ml) and dried in vacuo to give the title compound as a beige solid (21.5 g, 0.106 mol, 86%). LCMS: [M+H]+=203, Rt = 1.02 min, 100% purity. |
46% | With triethylamine; In ethanol; at 50℃; for 2h; | Example 5A8.7 g (53.5 mmol) of 4-fluorphenylhydrazine hydrochloride was suspended with 6.5 g (53.5 mmol) of ethoxymethylenemalononithle in 13 ml of ethanol, and 22.2 ml (160 mmol) of thethylamine were added. The reaction mixture was heated to 500C for 2 h. After cooling to room temperature the solvent was removed under reduced pressure. The remaining residue was treated with water (25 ml) and extracted three times with ethyl acetate. The organic layer was dried over sodium sulphate, filtered and the filtrate was concentrated under reduced pressure. The remaining residue was <n="60"/>purified by preparative MPLC (SiO2, eluent CH2CI2). 5.0 g (46% of theory) of the product were obtained as an oil, that solidifies over night.LC-MS (Method 1 ): RT = 1.06 minMS (ESI pos): m/z = 203 (M+H)+. |
General procedure: A stirred mixture of para-substituted phenylhydrazinehydrochloride (0.025 mol) was dissolved in H2O (30 mL), thenthe pH of the mixture was adjusted to pH 7-8 by the dropwiseaddition of 10% NaOH solution to form the free para-substitutedphenyl hydrazines, which were then refluxed for 3 h with ethoxymethylene malononitrile in an ethanol medium. After completionof the reaction, the reaction mixture was allowed to cool at room temperature, and the solid were filtered under vacuum. The crudeproducts obtained were recrystallized from anhydrous ethanol togive the light yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | at 180℃; for 3h; | Title compound 1A, <strong>[51516-70-2]5-amino-1-(4-fluoro-phenyl)-1H-pyrazole-4-carbonitrile</strong> (21.5 g, 0.106 mol) was suspended in formamide (200 ml). The suspension was heated to 180C for 3 hours and then allowed to cool to room temperature. To the reaction mixture was then added water (100 ml) and the resultant precipitate was collected by filtration, washed with water (2 x 100 ml), isopropyl alcohol (100 ml) and diethyl ether (100 ml), then dried on the filter to give the title compound as a beige solid (11.5 g, 55 mmol, 47%). This was then recrystalised from methanol to yield the title compound as an off-white solid (8.2 g, 35.8 mmol, 34%). LCMS: [M+H]+= 230, Rt = 1.09 min, 100% purity. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonia; In methanol; at 200℃; for 45h;Product distribution / selectivity; | Method B5-Amino-1-(4-fluorophenyl)-1/-/-pyra2thetale-4-carbonitrile (which may be prepared as described in J. Med. Chem., 1991 , 34, 2892-2898) (7.45g, 37mmol) and acetonitrile (56ml, 1.07mol) in 2M ammonia / methanol (150ml) were stirred and heated to 200C in a steel pressure vessel for 45 hours. The reaction mixture was cooled and the precipitate was filtered, washed with methanol and dissolved in ethyl acetate. The ethyl acetate solution was filtered in order to remove a small amount of insoluble solid and then concentrated in vacuo until appearance of precipitate. The ethyl acetate suspension was diluted with an equal volume of chloroform and the solid filtered and washed with 1 :1 chloroform / 40:60 petroleum ether to give the title compound (4.37g). LCMS: tRET = 2.42 min; MH+ = 244 A further 1.3g of title compound was obtained from the acetonitrile / 2M ammonia in methanol mother liquor using a similar work-up. |
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