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CAS No. : | 26621-44-3 |
Formula : | C3H3N3O2 |
M.W : | 113.08 |
MDL No. : | MFCD00159621 |
InChI Key : | MZRUFMBFIKGOAL-UHFFFAOYSA-N |
Pubchem ID : | 123419 |
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 27.41 |
TPSA ? Topological Polar Surface Area: Calculated from | 74.5 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from | 0.21 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by | 0.38 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from | 0.32 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from | -0.8 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by | -0.86 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions | -0.15 |
Log S (ESOL):? ESOL: Topological method implemented from | -1.18 |
Solubility | 7.52 mg/ml ; 0.0665 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (Ali)? Ali: Topological method implemented from | -1.51 |
Solubility | 3.49 mg/ml ; 0.0309 mol/l |
Class? Solubility class: Log S scale | Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by | -0.56 |
Solubility | 31.2 mg/ml ; 0.276 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 | No |
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 | -6.72 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 | 2.0 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) | 1.92 |
* 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 |
---|---|---|
91% | In benzonitrile; for 2h;Reflux; | A solution of 1 -nitro-1 H-pyrazole (4.23 gm, 37.4 mmol; Oakwood Products, Inc., West Columbia, SC) in benzonitrile (42 ml_) was heated to reflux for 2 hours. After cooling to 45 0C, the reaction mixture, which was starting to precipitate, was poured into 175 ml_ hexanes. A white solid precipitated. This was collected by vacuum filtration, rinsed repeatedly with hexane and dried under high vacuum to afford 3.85 grams (91 percent) of (l-27a) as a white solid; 1H NMR (400 MHz, DMSO-d6) delta 13.90 (1 H), 8.01 (1 H), 7.01 |
91% | In benzonitrile; at 180℃; for 3h; | Example 15Preparation of 3-(4-fluorophenylsulfonyl)-N-(5-methoxy-lH-pyrazol-3- vDisoq uinolin- 1-amine[00264] Step A: A stirred mixture of <strong>[7119-95-1]<strong>[7119-95-1]1-nitropyrazol</strong>e</strong> (3.45 g, 30.5 mmol) in benzonitrile (33 mL) was heated at 180 °C for 3 h. The mixture was cooled to rt, diluted with hexane and stirred at rt for 20 min. The precipitated solid was collected by filtration to afford 3-nitro-lH-pyrazole as a tan solid (3.16 g, 91percent). 1H NMR (300 MHz, DMSO-t/e) delta 13.94 (br s, 1H), 8.03 (d, J= 2.4 Hz, 1H), 7.03 (t, J= 2.4 Hz, 1H). |
91% | In benzonitrile; at 180℃; for 3h; | Step A: A stirred mixture of <strong>[7119-95-1]<strong>[7119-95-1]1-nitropyrazol</strong>e</strong> (3.45 g, 30.5 mmol) in benzonitrile (33 mL) was heated at 180° C. for 3 h. The mixture was cooled to rt, diluted with hexane and stirred at rt for 20 min. The precipitated solid was collected by filtration to afford 3-nitro-1H-pyrazole as a tan solid (3.16 g, 91percent). 1H NMR (300 MHz, DMSO-d6) delta 13.94 (br s, 1H), 8.03 (d, J=2.4 Hz, 1H), 7.03 (t, J=2.4 Hz, 1H). |
91% | With benzonitrile; at 180℃; for 3h; | A stirred mixture of <strong>[7119-95-1]<strong>[7119-95-1]1-nitropyrazol</strong>e</strong> (3.45 g, 30.5 mmol) in benzonitrile (33 mL) was heated at 180 °C for 3 h. The mixture was cooled to rt, diluted with hexane and stirred at rt for 20 min. The precipitated solid was collected by filtration to afford 3-nitro-lH-pyrazole as a tan solid (3.16 g, 91percent). H NMR (300 MHz, DMSO- 6) delta 13.94 (br s, 1H), 8.03 (d, J = 2.4 Hz, 1H), 7.03 (t, J = 2.4 Hz, 1H). |
79% | In benzonitrile; for 2h;Reflux; | Example 5 (S)-3-Cyclopentyl-N-[1-(2-methoxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionamide A solution of <strong>[7119-95-1]1-nitro-1H-pyrazole</strong> (4.00 g, 35.4 mmol) in 40 mL of benzonitrile was refluxed for 2 h. After being cooled to 25° C., the mixture was poured into hexanes (160 mL). A white solid precipitated which was filtered and dried in vacuo, to afford 3-nitro-1H-pyrazole (3.16 g, 79percent): H1-NMR (400 MHz, DMSO-d6) delta 7.01 (1H, d, J=2.4 Hz), 8.01 (d, 1H, J=3.4 Hz). |
79% | In benzonitrile; for 2h;Reflux; | A solution of <strong>[7119-95-1]1-nitro-1H-pyrazole</strong> (4.00 g, 35.4 mmol) in benzonitrile (40 mL) was refluxed for 2 h. After being cooled to 25° C., the mixture was poured into hexanes (160 mL). A white solid precipitated which was filtered and dried in vacuo, to afford 3-nitro-1H-pyrazole (3.16 g, 79percent). 1H-NMR (400 MHz, DMSO-d6) delta 7.01 (1H, d, J=2.4 Hz), 8.01 (d, 1H, J=3.4 Hz). Intermediate 2. |
79% | In benzonitrile; for 2h;Heating / reflux; | A solution of <strong>[7119-95-1]1-nitro-1H-pyrazole</strong> (4.00 g, 35.4 mmol) in 40 mL of benzonitrile was refluxed for 2 h. After being cooled to 25° C., the mixture was poured into 160 mL of hexanes. A white solid precipitated which was filtered and dried in vacuo, to afford 3-nitro-1H-pyrazole (3.16 g, 79percent). H1-NMR (400 MHz, DMSO-d6) delta: 7.01 (1H, d, J=2.4 Hz), 8.01 (d, 1H, J=3.4 Hz). |
79% | In benzonitrile; for 2h;Heating / reflux; | Example 15 (E)-4-{3-[2-(3-Chloro-4-methanesulfonyl-phenyl)-2-cyclopentyloxyimino-acetylamino]-pyrazol-1-ylmethyl}-benzoic acid methyl ester A solution of <strong>[7119-95-1]1-nitro-1H-pyrazole</strong> (4.00 g, 35.4 mmol) in 40 mL of benzonitrile was refluxed for 2 h. After being cooled to 25° C., the mixture was poured into hexanes (160 mL). A white solid precipitated which was filtered and dried in vacuo, to afford 3-Nitro-1H-pyrazole (3.16 g, 79percent): H1-NMR (400 MHz, DMSO-d6) delta7.01 (1H, d, J=2.4 Hz), 8.01 (d, 1H, J=3.4 Hz). |
56% | at 145℃; for 10h; | N-Nitropyrazole (2 g, 18 mmol) was heated at 145 °C for 10 h in a round-bottom flask. Then the product was purified by silica column chromatography using 5:95 v/v methanol/chloroform as eluent to afford 56percent of 3(5)-<strong>[7119-95-1]nitropyrazole</strong> as a white solid. |
51% | In methoxybenzene; at 145℃; | 1-Nitropyrazole (10 g, 88 mmol) was heated in 600 ml of anisole at 145°C overnight. The mixture was cooled in a freezer which caused a precipitate to form. The precipitate was collected to give 5.075 g of the title compound as a tan solid (51percent). [M+H] calc'd for C3H3N3O2, 114; found, 114. |
In methoxybenzene; at 145℃; | 3-Nitro-lH-pyrazolew; [539] [Ref.: Janssen, J.W.A.M. and Habraken, C.L., J. Org. Chem., 1971,36,3081.] A solution of l-nitro-ll/'-pyrazole (3.0g, 0.026 mol) in anisole (200mL) was heated at 145°C overnight. The mixture was cooled to rt, the white solid was collected by filtration and washed with hexanes. The mother liquid was diluted with hexanes (500mL) and cooled to -20°C, and the resulting off-white solid was collected and combined with the previous solid.LC-MS (ES, Pos.): 1 14 [MH+]. 'H NMR (DMSO-d6, 400 MHz): 5 = 7.04 (d, J= 2.5 Hz, 1H),8.04 (d, /= 2.5 Hz, 1H), 13.96 (br s, 1H). | |
In benzonitrile; at 180℃; for 3h; | A solution of 1.0 g of <strong>[7119-95-1]N-<strong>[7119-95-1]nitropyrazole</strong></strong> in 10 mL of benzonitrile was heated for 3 h at 180 °C, after cooling the reaction mixture was poured into 30 mL of hexane. 3-<strong>[7119-95-1]nitropyrazole</strong> was collected by filtration. The crude yield after washing with hexane and drying was 0.93 g (98percent). The solid was recrystallized from water. m.p. 174?175 °C. FT-IR (KBr, cm?1) 3180 (N?H), 1520 and 1351 cm?1 (NO2). 1H NMR (DMSO-d6) delta: 7.96 (d, 1, 5(3)-H), 6.96 (d, 1, 4-H). EI-MS: m/z 113 (M+·). Anal. Calcd for C3H3N3O2: C, 31.86; H, 2.67; N, 37.16. Found: C, 32.19; H, 2.84; N, 37.18. | |
at 180℃; | A 100mL one-neck flask equipped with a magnetic stirrer was added 5g of compound 1 and 15mL acetic acid, stirred, to give a clear solution. Under ice bath 3.5mL of fuming nitric acid was slowly added dropwise to the mixed solution, maintaining vigorous stirring, the reaction temperature does not exceed 30 deg. C. 10mL acetic anhydride was added to the mixture, after the addition, the mixture immediately became cloudy, to give a white turbid liquid. After the addition it was stirred at room temperature, until the solution became clear, about 2.5h. After completion of the reaction, the solution was slowly poured into 100mL crushed ice and with vigorous stirring, potassium carbonate was added portionwise until the mixture was neutral, white precipitate was filtered to give 5.6g of white powdery crystals, the filtrate was extracted with ethyl acetate, the combined organic phase was dried over anhydrous sodium sulfate, the solvent was removed by rotary evaporation to give pale yellow crystals 1.3490g, total crude was 6.9490g, yield 91.9percent recrystallized from benzene. Weigh three 100mg compound 2 into thick-walled pressure bottle, gradually heated to 160 deg. C, 180 deg. C, 200 deg. C, the reaction at this temperature for 1 ~ 3h to obtain compound 3, the results shown in Table 1. | |
In benzonitrile; at 180℃; for 3.5h; | <strong>[7119-95-1]N-<strong>[7119-95-1]nitropyrazole</strong></strong> is dissolved in benzonitrile, heated to 180 ° C, incubated for 3.5 h,cooled to 50-60 ° C after completion of thereaction, and added to n-hexane to make 3-nitrate The pyrazole is precipitated, filtered and dried to give 3-<strong>[7119-95-1]nitropyrazole</strong>; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; | Step 1c Preparation of the Nitropyrazole 4. 3-Nitropyrazole (1.13 g, 10 mmol) in dry DMF (10 ml), under argon, was treated with anhydrous K2CO3 (2.7 g, 15 mmol) and then, dropwise, with methyl-4-bromobutyrate (1.82 g, 10.05 mmol) at RT. After stirring overnight the DMF was removed and the residue partitioned between H2O and EtOAc. The combined organic extracts were washed (H2O and brine), dried (Na2SO4), filtered and evaporated to give a mixture of 4 and 6 (2.05 g) as a pale yellow oil. MS (ES+) m/z 214 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate; In acetonitrile; at 80℃; for 2h;Inert atmosphere; | 6-(3-Nitro-pyrazol-1-yl)-hexan-2-oneIn a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a suspension of 5-nitro-1H-pyrazole (3.69 g, 29.35 mmol) and Cs2CO3 (10.53 g, 32.28 mmol) in AcCN (34.0 mL) was treated with a solution of 6-bromo-hexan-2-one (5.78 g, 32.28 mmol) in AcCN (26.0 mL). The reaction mixture was stirred at 80 C. for 2 h. Water (123 mL) and EA (185 mL) were added to the cooled reaction mixture. The aq. layer was extracted with EA (185 mL) and the combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (50:50 hept-EA) gave the title compound. TLC: rf (50:50 hept-EA)=0.21. LC-MS-conditions 02: tR=0.82 min; [M+H]+=212.28. |
Tags: 26621-44-3 synthesis path| 26621-44-3 SDS| 26621-44-3 COA| 26621-44-3 purity| 26621-44-3 application| 26621-44-3 NMR| 26621-44-3 COA| 26621-44-3 structure
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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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