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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. : | 1118-61-2 |
Formula : | C4H6N2 |
M.W : | 82.10 |
SMILES Code : | CC(N)=CC#N |
MDL No. : | MFCD00008071 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H302-H311-H317 |
Precautionary Statements: | P261-P264-P270-P272-P280-P301+P312+P330-P302+P352+P312-P333+P313-P405-P501 |
Class: | 6.1 |
UN#: | 3439 |
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 |
---|---|---|
73% | Stage #1: With hydrogenchloride In water for 12 h; Reflux Stage #2: With sodium hydroxide In water |
General procedure: 3-aminocrotononitrile (48, 10 mmol) was added to a suspension of the appropriate arylhydrazine 49a-l (10 mmol) in 12M HCl-H2O (12 mL, 1:3), and the resulting mixture was heated under reflux for 12 hours and then cooled and neutralized with 2.5M sodium hydroxide solution. The suspension was extracted with CH2Cl2 (3x30 mL). The organic phases were washed with brine (20 mL), dried and the solvent evaporated in vacuo. The residue oil was triturated with hexane to obtain a solid which was separated by filtration. Subsequent chromatography was performed where indicated. |
60% | Stage #1: With hydrogenchloride In water at 100℃; for 18 h; Stage #2: With sodium hydroxide In water |
2.789 g (15.83 mmol) of 2-(trifluoromethyl)-phenylhydrazine was prepared in 15 ml of IN hydrochloric acid and 1.378 g (16.781 mmol) of 3-aminocrotonic nitrile was added. The mixture was stirred for 18 h at 1000C. After cooling, the pH value of the mixture was adjusted with IN sodium hydroxide solution to pH > 12. It was extracted with dichloromethane three times. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated in a rotary evaporator at reduced pressure. The product was dried at high vacuum and purified by preparative HPLC (eluent: acetonitrile/water, gradient 20:80 -->90:10). We obtained 2.50O g (60percent of theor., purity 91percent according to HPLC) of the target compound.LC-MS (method 10): R, = 1.09 min; MS (EIpos): m/z = 242 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In pentan-1-ol; for 20h;Heating / reflux; | To a solution of 16.4 g (0.2 mol) of 3-aminocrotononitrile in 100 cm3 of n-pentanol were added 19.4 g (0.22 mol) of tert-butylhydrazine. This solution was heated at reflux for 20 hours. The n-pentanol was subsequently distilled off under reduced pressure. A pale yellow solid was obtained, which was taken up in 100 cm3 of isopropyl ether at room temperature and filtered on a sinter funnel. After drying under vacuum at 40 C., 18 g of the expected product were obtained in the form of a pale yellow solid, the melting point of which was from 172 to 175 C. | |
With triethylamine; In ethanol;Reflux; | Step (i): Preparation of l-(tert-Butyl)-3-methyl-lH-pyrazol-5-amineTo a mixture of 3-aminobut-2-enenitrile (60 g, 731 mmol) and tert-butylhydrazine (96 g, 731.1 mmol) in ethanol (35 ml), triethylamine (220 ml, 2195 mmol) was added. The mixture was refluxed for 12-16 h. The reaction mixture was then concentrated under reduced pressure. The concentrate was extracted with water (100 ml) and ethylacetate (700 ml). The organic layer was washed with brine and dried over Na2SC>4 and concentrated under reduced pressure to obtain the title product..Η ΝΜΡν (400 MHz, CDC13) δ 5.37 (s, 1H), 3.51 (bs, 2H), 2.14 (s, 3H), 1.61 (s, 9H). MS (m/z): 154 (M++l, 100%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | 2.000 g (11.453 mmol) of <strong>[6971-45-5]2-methoxyphenylhydrazine hydrochloride</strong> was put in 10 ml of IN hydrochloric acid and 0.997 g (12.140 mmol) of 3-aminocrotonic nitrile was added. The mixture was stirred for 18 h at 1000C. After cooling, the pH value of the mixture was adjusted with IN sodium hydroxide solution to pH > 12. It was extracted with dichloromethane three times. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated in a rotary evaporator at reduced pressure. The product was dried under high vacuum. We obtained 2.430 g (purity according to LC-MS 91%, 95% of theor.) of the target compound.LC-MS (method 3): R, = 0.31 min; MS (EIpos): m/z = 204 [M+H]+. | |
86% | IM07: 2-(2-Methoxy-phenyl)-5-methyl-2H-pyrazol-3-ylamineTo a solution of (2-methoxy-phenyl)-hydrazine HCl salt (10.0 g, 57.3 mmol) in concentrated aqueous HCl (50 mL) was added 3-amino-but-2-enenitrile (5.0 g, 60.9 mmol) at room temperature. The reaction temperature was increased to 100 C. and the mixture was stirred at this temperature for 18 h. The reaction mixture was cooled to room temperature and then poured into ice-cold 2N NaOH solution (200 mL). The resulting mixture was filtered. The remanens was washed with water (200 mL) and dried in vacuo to give the title compound as an off-white solid (10.0 g, 86%). 1H NMR (DMSO-d6, 400 MHz) delta 7.39-7.35 (1H, m), 7.24-7.22 (1H, m), 7.17-7.15 (1H, m), 7.03-6.99 (1H, m), 5.21 (1H, s), 4.76 (2H, s), 3.78 (3H, s), 2.02 (3H, s). | |
86% | With hydrogenchloride; at 20 - 100℃; for 18h; | General procedure: To a solution of (2-methoxy-phenyl)-hydrazine HCI salt (10.0 g, 57.3 mmol) in concentrated aqueous HCI (50 mL) was added 3-amino-but-2-enenitrile (5.0 g, 60.9 mmol) at room tem- perature. The reaction temperature was increased to 100 C and the mixture was stirred at this temperature for 18 h. The reaction mixture was cooled to room temperature and then poured into ice-cold 2N NaOH solution (200 mL). The resulting mixture was filtered. The re- manens was washed with water (200 mL) and dried in vacuo to give the title compound as an off-white solid (10.0 g, 86 %). 1 H NMR (DMSO-d6, 400 MHz) delta 7.39-7.35 (1 H, m), 7.24-7.22 (1 H, m), 7.17-7.15 (1 H, m), 7.03-6.99 (1 H, m), 5.21 (1 H, s), 4.76 (2H, s), 3.78 (3H, s), 2.02 (3H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; for 17.0h;Heating / reflux; | (b). 4-(3-Ethoxy-4-hvdroxy-5-nitro-phenviy2-methyl-5-oxo-7-propyl-l,4,5, 6,7,8- hexahydro-quinoline-3 -carbonitrileA mixture of <strong>[178686-24-3]3-ethoxy-4-hydroxy-5-nitro-benzaldehyde</strong> (1.5 g), 3-aminocrotonitrile (584 mg) and 5-propylcyclohexane-l,3-dione (1.09 g) in ethanol (60 ml) was heated at reflux for 17 h. The mixture was concentrated in vacuo. The residue was purified by chromatography on silicagel in heptane/ethyl acetate 1/0 - > 0/1 (v/v) as eluent. EPO <DP n="43"/>Yield: 1.3 g. MS-ESI: [M+H]+ = 412.3 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | General procedure: In a 2-5mL microwave vial containing a stir bar, 3-aminocrotonitrile (164 mg, 2mmol) and 5 mL of 1M HCl were combined with stirring to give a 0.4 M solution of starting material. Next, phenylhydrazine (216 mg, 2 mmol) was added to the solution. The microwave vial was then sealed with an aluminum cap and irradiated in the microwave reactor at 150 C for 10 m with the absorbance set to “very high.” After cooling, the orange sludge-containing heterogeneous solution was basified with 10% NaOH and was sonicated for 5 m to produce a visible solid precipitate. The precipitate was filtered, washed twice with D.I. water, and then dried to yield the product as a light orange solid (292 mg, 84% yield). For compounds that do not readily precipitate, the product can be isolated by extracting the basic aqueous layer 3x with dichloromethane (DCM). The combined organic layers are dried over magnesium sulfate, filtered and evaporated under reduced pressure to obtain the product. | |
With hydrogenchloride; In water; | 5-Amino-1-(4-fluorophenyl)-3-methyl-pyrazole 4-Fluorophenylhydrazine HCl (60.0 g.) 175 ml. water, 70 ml. concentrated hydrochloric acid and 28.8 g. 3-amino-2-butene nitrile were refluxed one hour. The solution was cooled and made basic with concentrated ammonia. The solid was filtered and crystallized from ether to get 51.05 g. product, mp 108-110, which was converted to the HCl salt mp 227-229 Analyzed for C10 H10 FN3.HCl: Theoretical; C=52.76, H=4.87, N=18.47 Found; C=52.96, H=4.87, N=18.36 | |
With hydrogenchloride; In water; | 5-Amino-1-(4-fluorophenyl)-3-methyl-pyrazole 4-Fluorophenylhydrazine HCl (60.0 g.) 175 ml. water, 70 ml. concentrated hydrochloric acid and 28.8 g. 3-amino-2-butene nitrile were refluxed one hour. The solution was cooled and made basic with concentrated ammonia. The solid was filtered and crystallized from ether to get 51.05 g. product, mp 108-110, which was converted to the HCl salt mp 227-229 Analyzed for C10 H10 FN3 ·HCl: Theoretical; C=52.76, H=4.87, N=18.47. Found; C=52.96, H=4.87, N=18.36. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With sodium hydroxide; In water; at 90℃; for 18h; | Intermediate P : 1 -tert-Butyl-3-methyl-1 H-pyrazol-5-amine tert- Butylhydrazine hydrochloride (15.2 g, 122 mmol) was added to the aqueous solution of sodium hydroxide (60 mL, 2M, 122 mmol) and stirred until dissolution of a solid. To the mixture 3-aminobut-2-enenitrile (10 g, 122 mmol) was added. The reaction mixture was stirred while heating at 90C for 18 hours, then cooled to room temperature and extracted with dichloromethane (3 χ 50 mL). Organic layers were combined, washed with brine, dried (Na2S04) and concentrated under reduced pressure to obtain title product as a white, amorphous solid with the yield of 92% (17.2 g, 1 12 mmol). 1H NMR (500 MHz, CDCl3) δ 7.25 (t, J=8.3 Hz, 1 H), 6.50 (d, J=8.3 Hz, 2H), 3.88 (s, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | General procedure: 3-aminocrotononitrile (48, 10 mmol) was added to a suspension of the appropriate arylhydrazine 49a-l (10 mmol) in 12M HCl-H2O (12 mL, 1:3), and the resulting mixture was heated under reflux for 12 hours and then cooled and neutralized with 2.5M sodium hydroxide solution. The suspension was extracted with CH2Cl2 (3x30 mL). The organic phases were washed with brine (20 mL), dried and the solvent evaporated in vacuo. The residue oil was triturated with hexane to obtain a solid which was separated by filtration. Subsequent chromatography was performed where indicated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; at 20℃;Reflux; | Intermediate 23-Methyl-l-(l-methylethyl)-6-oxo-6,7-dihydro-lH-pyrazolo[3,4-6]pyridine-4- carboxylic acidStep 1:3-Methyl-l-(l-methylethyl)-lH-pyrazol-5-amine3-Amino-2-butenenitrile (33.3 g, 0.41 mol) and ethanol (170 mL) were combined and stirred at room temperature for 30 min., after which time isopropylhydrazine (50 g, 0.67 mol) was added at once. After stirring at room temperature for 5 min., the contents were then heated at reflux for 10 h. After cooling to room temperature, the mixture was concentrated in vacuo to give the desired product (85 g) which was used in the next step directly. 1H NMR (400 MHz, DMSO-d6) ? ppm 1.21 (d, 6 H, J =6.4 Hz), 1.94 (s, 3H), 4.21 (m, 1H), 4.93 (s, 2H), 5.02 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With hydrogenchloride; In water; for 0.416667h;Heating; | General procedure: To a solution of the corresponding arylhydrazine (1a-e) (10 mmol) in concentrated hydrochloric acid (5 mL), 820 mg of 3-aminocrotonitrile (2) (10 mmol) was added with magnetic stirring. The mixture was left to react for 10 minutes and then more HCl was added (5 mL) while heating for 15 additional minutes. After completion of the reaction, a yellow solution was obtained which was then cooled by addition of crushed ice and neutralized with concentrated ammonium hydroxide. Finally, the formed precipitate corresponding to aminopyrazoles 3a-e, was vacuum filtered and washed with cold water. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | General procedure: In a 2-5mL microwave vial containing a stir bar, 3-aminocrotonitrile (164 mg, 2mmol) and 5 mL of 1M HCl were combined with stirring to give a 0.4 M solution of starting material. Next, phenylhydrazine (216 mg, 2 mmol) was added to the solution. The microwave vial was then sealed with an aluminum cap and irradiated in the microwave reactor at 150 C for 10 m with the absorbance set to ?very high.? After cooling, the orange sludge-containing heterogeneous solution was basified with 10% NaOH and was sonicated for 5 m to produce a visible solid precipitate. The precipitate was filtered, washed twice with D.I. water, and then dried to yield the product as a light orange solid (292 mg, 84% yield). For compounds that do not readily precipitate, the product can be isolated by extracting the basic aqueous layer 3x with dichloromethane (DCM). The combined organic layers are dried over magnesium sulfate, filtered and evaporated under reduced pressure to obtain the product. |
Tags: 3-Aminocrotononitrile | 1118-61-2
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H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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