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Search for reports by entering the product batch number.
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CAS No. : | 7400-27-3 |
Formula : | C4H13ClN2 |
M.W : | 124.61 |
SMILES Code : | NNC(C)(C)C.[H]Cl |
MDL No. : | MFCD00012947 |
InChI Key : | DDPWVABNMBRBFI-UHFFFAOYSA-N |
Pubchem ID : | 81889 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H316-H319 |
Precautionary Statements: | P501-P270-P264-P280-P337+P313-P305+P351+P338-P332+P313-P301+P312+P330 |
Num. heavy atoms | 7 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 1.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 33.85 |
TPSA ? Topological Polar Surface Area: Calculated from | 38.05 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 0.84 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 1.05 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | 1.04 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | -0.76 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | 0.44 |
Log S (ESOL):? ESOL: Topological method implemented from | -1.08 |
Solubility | 10.5 mg/ml ; 0.084 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (Ali)? Ali: Topological method implemented from | -1.22 |
Solubility | 7.48 mg/ml ; 0.06 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -0.68 |
Solubility | 26.0 mg/ml ; 0.208 mol/l |
Class? Solubility class: Log S scale | Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg | High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg | Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) | No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) | No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) | No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) | No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) | No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) | No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from | -6.46 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from | 0.0 |
Ghose? Ghose filter: implemented from | None |
Veber? Veber (GSK) filter: implemented from | 0.0 |
Egan? Egan (Pharmacia) filter: implemented from | 0.0 |
Muegge? Muegge (Bayer) filter: implemented from | 2.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat | 0.55 |
PAINS? Pan Assay Interference Structures: implemented from | 0.0 alert |
Brenk? Structural Alert: implemented from | 1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from | No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) | 1.42 |
* 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 |
---|---|---|
Formyl-3-oxo-propionic acid ethyl ester (75.85 g, 525.6 mmol) was dissolved in ethanol (1 L) at room temp. Tert-butylhydrazine hydrochloride (65.5 g, 525.6 mmol) was added at room temp and the reaction temperature gradually increased to 32° C. The flask was then placed in an ice-bath to cool it back to 20° C. It took ca. 1 h for t-butylhydrazine to fully dissolve. The solution was stirred at room temp. for 3 h. The reaction mixture was cooled in an ice-bath. Sodium hydroxide (4N, 152.4 g) was added to neutralize the hydrochloric acid. Most of the ethanol was then removed in vacuo and methanol (300 ml) was added followed by additional sodium hydroxide (4N, 304.8 g, 1.05 mol). The internal temperature gradually rose to 32° C. The reaction flask was then placed in a water bath to cool it back to room temp. and the reaction was allowed to stir at room temp. for 18 h. Methanol (300 ml) was then removed in vacuo with the water bath temperature kept below 30° C. The reaction mixture was then cooled to 0° C. and hydrochloric acid (6N, 190 ml) was added slowly to keep internal temperature below 15° C. The solution was adjusted to pH=2. The resulting suspension was allowed to stir in the ice-bath for 2 h, and the solid was filtered. After drying at 60° C. in vacuo for 2.5 days, 1-tert-butyl-1H-pyrazole-4-carboxylic acid (56.06 g) of off-white solid was collected. The mother liquor was extracted 3 times with dichloromethane (200 ml.x.3). The combined organic layer was washed once with brine (100 ml) and dried over magnesium sulfate. After concentrating in vacuo and drying, 16.5 g of yellowish solid was collected. The crude material was crystallized in hot iso-propyl acetate (25 ml) and heptane (25 ml). After cooling to room temp, the solid was filtered off and the cake was washed with mixed solvent of isopropyl acetate and heptane (1/1 (v/v, 14 ml) and dried in oven at 60° C. in vacuo for 5 h. A second crop of 1-tert-butyl-1H-pyrazole-4-carboxylic acid (7 g) was collected as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With triethylamine; In ethanol; water; at 78.0℃; for 3.0h; | Dissolve tert-butylhydrazine hydrochloride (8 g, 64.20 mmol) and triethylamine (6.50 g, 64.20 mmol) in 500 mL of absolute ethanol. Then, 2-ethoxymethylenemalononitrile (7.83 g, 64.20 mmol) was slowly added dropwise to the reaction flask with stirring. It was heated to reflux at 78 C. After about 3 h, the reaction was monitored by TLC (developer: PE / EtOAc = 1: 1). After the reaction solution was cooled to room temperature, the solvent was concentrated under reduced pressure to remove the solvent, and 100 mL of water and CH 2 Cl 2 (300 mL × 3) were added for extraction. The organic phases were combined, dried by adding an appropriate amount of anhydrous sodium sulfate, and concentrated to obtain an orange-yellow viscous solid. The obtained crude product was dissolved in 60 mL of an ethyl acetate-n-hexane (1: 9) mixed solution, sonicated for about 5 min, and allowed to stand. Observed that a large number of crystal forms precipitated, and filtered (washed 3 times with the ethyl acetate-n-hexane mixed solution). Drying gave 10.11 g of 1-tert-butyl-5-amino-1H-pyrazole-4-carbonitrile as an orange solid product, yield: 96%. |
96% | With triethylamine; In ethanol; at 78.0℃; for 3.0h; | tert-butylhydrazine hydrochloride (8g, 64.20mmol) and triethylamine (6.50g, 64.20mmol) In 500 mL of absolute ethanol, 2-ethoxymethylenemalononitrile (7.83 g, 64.20 mmol) was slowly added dropwise to the reaction flask with stirring.It was heated to reflux at 78 C. After about 3 h, the reaction was monitored by TLC (developer: PE / EtOAc = 1: 1).After the reaction solution was cooled to room temperature, the solvent was concentrated under reduced pressure to remove the solvent, and 100 mL of water and CH2Cl2(300 mL × 3) were added for extraction. The organic phases were combined, dried by adding an appropriate amount of anhydrous sodium sulfate, and concentrated to obtain an orange-yellow viscous solid.The obtained crude product was dissolved in 60 mL of an ethyl acetate-n-hexane (1: 9) mixed solution, sonicated for about 5 min, and allowed to stand. Observed that a large number of crystal forms precipitated, and filtered (washed 3 times with the ethyl acetate-n-hexane mixed solution) Drying gave 10.11 g of 1-tert-butyl-5-amino-1H-pyrazole-4-carbonitrile as an orange solid product, yield: 96%. |
94% | To a suspension of fe/ -butylhydrazine hydrochloride (15.0 g, 120.4 mmol) in ethanol (600 ml_) was added triethylamine (16.8 ml_, 120.4 mmol). The mixture was stirred for 60 min until the hydrazine had dissolved. Ethoxymethylenemalononitrile (14.7 g, 120.4 mmol) was added in portions and the reaction mixture was heated to 80 C and stirred at this temperature overnight. The reaction mixture was concentrated to dryness and the obtained residue was taken up in EtOAc. The organic layer was washed with water, dried over Na2S04, filtered and concentrated under reduced pressure. The solid was then recrystallized in DCM to afford 5-amino-1 -fe/?-butyl-pyrazole-4-carbonitrile (18.6 g, 1 13.4 mmol, 94% yield) as a light yellow solid. LC-MS (ES+, method 1): 1 .36 min, m/z 165.1 [M+H]+ |
83% | With triethylamine; In ethanol; for 3.0h;Reflux; | In tert-butylhydrazine hydrochloride (8.67 g, 69.6 mmol)Was added triethylamine (9.7 mL, 69.6 mmol)After adding anhydrous ethanol (460 mL), the mixture was stirred and dissolved at room temperature,Ethoxymethylenemalononitrile (8.5 g, 69.6 mmol) was added in small portions.After heating the solution to reflux for 3 hours,After cooling, the solvent was evaporated to give an orange solid.And extracted with ethyl acetate (0.5 L) and water (0.25 L)After drying by adding magnesium sulfate,The organic layer was evaporated to give an orange-yellow solid.The resulting solid was continuously washed with a 10% ethyl acetate in cyclohexane solution to give a crystalline solid5-amino-1-tert-butyl hydrogen - pyrazol-4-cyano 9.54g(Yield: 83%). |
83% | With triethylamine; In ethanol; at 20.0℃; for 3.0h;Reflux; | Triethylamine (9.7mL, 69.6mmol) was added to tert-butylhydrazine hydrochloride (8.67g, 69.6mmol) After adding absolute ethanol (460mL) and stirring at room temperature to dissolve, Ethoxymethylenemalononitrile (8.5 g, 69.6 mmol) was added in small portions, the solution was heated to reflux for 3 hours, and then the solvent was evaporated in vacuo to obtain a crude orange product. It was extracted with a mixed solution of ethyl acetate (0.5 L) and water (0.25 L), dried over anhydrous magnesium sulfate, and the organic layer was evaporated to obtain an orange solid. Continue to wash the obtained solid with a cyclohexane solution containing 10% ethyl acetate to obtain crystalline solid 5-amino-1-tert-butyl 1hydro-pyrazole-4-cyano 9.54g (yield 83% ). |
64.4% | With triethylamine; In ethanol; for 3.0h;Heating / reflux; | A mixture of t-butylhydrazine hydrochloride (4.67 g, 53 mmol) and triethylamine (5.35 g, 53 mmol) in anhydrous ethanol (250 ml) was stirred and ethoxymethylene malononitrile (6.47 g, 53 mmol) was slowly added in portions. The mixture was heated at reflux for 3 hr. The solvent was removed in vacuo and the product was crystallized from ethyl acetate -hexane followed by ether to afford the title compound as light pale brown crystals (5.6 g, 64.4 %); LC/MS, API-ES, Neg, (M-H)", 163.0. |
With triethylamine; In ethanol; for 3.0h;Heating / reflux; | A mixture of t-butylhydrazine hydrochloride (4.67 g, 53 mmol) and triethylamine (5.35 g, 53 mmol) in anhydrous ethanol (250 ml) was stirred and ethoxymethylene malononitrile (6.47 g, 53 mmol) was slowly added in portions. The mixture was heated at reflux for 3 hr. The solvent was removed in vacuo and the product was crystallized from ethyl acetate - hexane followed by ether to afford 5-amino-l-tert-butyl-lH-pyrazole-4-carbonitrile as light pale brown crystals (5.6 g, 34.1 mmol); LC/MS, API-ES, Neg, (M-H)", 163.0. | |
With triethylamine; In ethanol; at 82.0℃; for 3.0h;Inert atmosphere; | [0814] Example 1: 5-amino-1-(tert-butyl)-1H-pyrazole-4-carbonitrile (I1): . In a 250mL flame-dried argon purged round bottom flask, triethylamine (1.78g, 17.7mmol), and t- butyl hydrazine hydrochloride (1.56g, 12.5mmol) are dissolved in anhydrous ethanol (85mL). Ethoxymethylenemalononitrile (1.98g, 17.7mmol) is added slowly and reaction mixture is brought to reflux at 82C for 3 hours. The solvent is removed in vacuo and 10% ethyl acetate / hexane is added (5mL) and the mixture is sonicated (or simply utilize recrystallization from 10% ethyl acetate / hexane). The resulting crystalline solid is filtered, and washed with ether to yield I1. LC-MS (ES+) calcd for C8H12N4 (M+H)+ 165.11, found 165.05. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Synthesis of 1-tert-butyl-1H-pyrazol-5-amine To 600 ml of ethanol were successively added 59.94 g of tert-butylhydrazine hydrochloride, 79.3 g of sodium acetate and 50 ml of 2-chloroacrylonitrile at room temperature, followed by stirring the reaction mixture at 80 C. for 12 hours. After removing the solvent in vacuo, water was added to the residue. The mixture was neutralized with sodium hydrogen carbonate, and extracted with ethyl acetate. The obtained ethyl acetate solution was washed with brine, dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated in vacuo. The obtained residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=2/1-1/2) to give the title compound as a pale yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium acetate; In ethanol; at 80℃; for 18.0h; | tert-Butylhydrazinehydrochloride (5.99 g, 48.1 mmol) was added to EtOH (60 mL) to form a slurry. To this was added NaOAc (7.93 g, 96.7 mmol) and 2-chloroacrylonitrile (5 mL,62.6 mmol). The solution was heated to 80 C for 18 h, cooled, and the solvent removed in vacuo. The residue was slowly diluted with distilled H2O (35 mL) and partitioned between sat. aq NaHCO3 (40 mL) and EtOAc (40 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (2 × 20 mL). The organic layers were combined, washed with brine (20 mL), dried (MgSO4), and the solvent removed in vacuo to afford a red oil; yield: 7.95 g (91%); bp 93-94C/0.9 Torr (yellow liquid). The product was a 5:1 mixture of the title compound 6c and its 1-tert-butyl-3-amino isomer. The crude product was used to prepare the Meldrum?s acid derivative 3c, which was purified by recrystallization (see below). |
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 |
---|---|---|
59.1 mg | With hydrogenchloride; In ethanol; water; at 20℃; | Example 55 Ethyl 1-(tert-butyl)-5-(4-fluorophenyl)-1H-pyrazole-3-carboxylate To a solution of <strong>[31686-94-9]ethyl 4-(4-fluorophenyl)-2,4-dioxobutanoate</strong> (55.9 mg, 0.235 mmol) in ethanol (2.5 mL) was slowly added tert-butyl hydrazine hydrogen chloride (48.0 mg, 0.378 mmol). Following the addition of 1M HCl 0.5 mL thereto, the reaction mixture was stirred overnight at room temperature. When the reaction was completed as monitored by TLC (Hexane:EtOAc=6:1), the reaction mixture was concentrated in vacuo. After extraction with dichloromethane and water, the organic layer thus formed was dried over anhydrous magnesium sulfate, filtered, and concentrated. The concentrated filtrate was purified by column chromatography (Hexane:EtOAc=6:1) to afford the title compound (59.1 mg, 87%, yellow solid). 1H NMR (300 MHz, CDCl3) delta 7.38-7.32 (m, 2H), 7.17-7.11 (m, 2H), 6.71 (s, 1H), 4.43 (q, J=7.1 Hz, 2H), 1.53 (s, 9H), 1.43 (t, J=7.1 Hz, 3H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
YYY-4 (40 mg, 0.096 mmol) is dissolved in N,N-dimethylacetamide (1 ml). HATU (40.3 mg, 0.106 mmol) is added and the mixture is stirred to result a solution. To the resulting solution is added to <strong>[57297-29-7]cyclopropanecarboximidamide hydrochloride</strong> (17.4 mg, 144 jtmol), followed by diisopropylamine (5 1.830 iL, 0.288 mmol). The mixture is then shaken at rt for 3 hours. A solution of t-butylhydrazine hydrochloride (18 mg, 144 imol) in DMA (0.5 mL) is added followed by acetic acid (55 iL, 0.960 mmol). The mixture is shaken at 80 °C for 3 hours. The reaction mixture is purified by reverse phase HPLC to obtain Example 36. |
Tags: 7400-27-3 synthesis path| 7400-27-3 SDS| 7400-27-3 COA| 7400-27-3 purity| 7400-27-3 application| 7400-27-3 NMR| 7400-27-3 COA| 7400-27-3 structure
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H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
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 |
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