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[ CAS No. 2075-46-9 ] {[proInfo.proName]}

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Chemical Structure| 2075-46-9
Chemical Structure| 2075-46-9
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Product Details of [ 2075-46-9 ]

CAS No. :2075-46-9 MDL No. :MFCD00159626
Formula : C3H3N3O2 Boiling Point : -
Linear Structure Formula :(C3H3N2)NO2 InChI Key :XORHNJQEWQGXCN-UHFFFAOYSA-N
M.W : 113.08 Pubchem ID :16376
Synonyms :
Chemical Name :4-Nitro-1H-pyrazole

Calculated chemistry of [ 2075-46-9 ]      Expand+

Physicochemical Properties

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 : 74.5 ?2

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.96 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.16
Log Po/w (XLOGP3) : 0.04
Log Po/w (WLOGP) : 0.32
Log Po/w (MLOGP) : -1.62
Log Po/w (SILICOS-IT) : -0.86
Consensus Log Po/w : -0.39

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -0.96
Solubility : 12.3 mg/ml ; 0.109 mol/l
Class : Very soluble
Log S (Ali) : -1.16
Solubility : 7.87 mg/ml ; 0.0696 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -0.56
Solubility : 31.2 mg/ml ; 0.276 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.66

Safety of [ 2075-46-9 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338-P310 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 2075-46-9 ]

* 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.

  • Downstream synthetic route of [ 2075-46-9 ]

[ 2075-46-9 ] Synthesis Path-Downstream   1~11

  • 1
  • [ 7119-95-1 ]
  • [ 2075-46-9 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid; at -10 - 20℃; 4-Nitro-lJH-pyrazoIe=N; [547] [Ref: Huettel, R. and Buechele, F., Chem. Ber. 1955, 88, 1586-1590] 1-Nitro-l/Z'-pyrazole (2.2g, 0.019 mol) was dissolved in sulfuric acid (lOmL) at-10°C, and theresulting mixture was slowly warmed to rt overnight. The solution was added to ice (lOOg)dropwise, and the resulting white solid was collected by filtration and washed with water.The aqueous phase was extracted with EtOAc (3x30mL), the combined organic phases werewashed with brine (2x30mL), and dried over anhydrous sodium sulfate. Evaporation underreduced pressure provided an off-white solid, which was combined with the first solid anddried in vacua to provide the title compound. LC-MS (ES, Pos.): 1 14 [MH+]. 'H NMR(DMSO-d6, 400 MHz): 8 = 8.27 (s, 1H), 8.90 (s, 1H), 13.96 (br s, 1H).
Concentrated sulphuric acid (80 ml) was added dropwise to a stirred sample of <strong>[7119-95-1]<strong>[7119-95-1]1-nitropyrazol</strong>e</strong> (20.3 g) that was cooled in an ice-bath. The resultant mixture was stirred for20 16 hours and allowed to warm to ambient temperature. The mixture was poured onto ice and stirred for 20 minutes. The resultant solid was isolated and washed with water. The filtrate was neutralised by the addition of potassium carbonate and extracted with diethyl ether. The recovered solid was added to the diethyl ether solution and the resultant solution was washed with a saturated aqueous sodium chloride solution, dried over magnesium sulphate and filtered.25 Petroleum ether (b.p. 60-80°C) was added to the filtrate which was concentrated by evaporation to a volume of about 50 ml. A precipitate formed which was isolated by filtration. There was thus obtained 4-<strong>[7119-95-1]nitropyrazole</strong> (16 g); 1HNMR: (DMSOd6 + CF3CO2H) 8.57 (s, 2H).
With sulfuric acid; at 0℃; for 16h; Concentrated sulphuric acid (80 ml) was added dropwise to a stirred sample of <strong>[7119-95-1]<strong>[7119-95-1]1-nitropyrazol</strong>e</strong> (20.3 g) that was cooled in an ice-bath. The resultant mixture was stirred for 16 hours and allowed to warm to ambient temperature. The mixture was poured onto ice and 0 stirred for 20 minutes. The resultant solid was isolated and washed with water. The filtrate was neutralised by the addition of potassium carbonate and extracted with diethyl ether. The <n="105"/>recovered solid was added to the diethyl ether solution and the resultant solution was washed with a saturated aqueous sodium chloride solution, dried over magnesium sulphate and filtered.Petroleum ether (b.p. 60-80°C) was added to the filtrate which was concentrated by evaporation to a volume of about 50 ml. A precipitate formed which was isolated by filtration. There was thus obtained 4-<strong>[7119-95-1]nitropyrazole</strong> (16 g); 1HNMR: (DMSOd6 + CF3CO2H) 8.57 (s,2H).
With sulfuric acid; at 0 - 25℃; for 16h; Concentrated sulphuric acid (80 ml) was added dropwise to a stirred sample of <strong>[7119-95-1]<strong>[7119-95-1]1-nitropyrazol</strong>e</strong> (20.3 g) that was cooled in an ice-bath. The resultant mixture was stirred for 16 hours and allowed to warm to ambient temperature. The mixture was poured onto ice and stirred for 20 minutes. The resultant solid was isolated and washed with water. The filtrate was neutralised by the addition of potassium carbonate and extracted with diethyl ether. The recovered solid was added to the diethyl ether solution and the resultant solution was washed with a saturated aqueous sodium chloride solution, dried over magnesium sulphate and filtered. Petroleum ether (b.p. 60-800C) was added to the filtrate which was concentrated by evaporation to a volume of about 50 ml. A precipitate formed which was isolated by filtration. There was thus obtained 4-<strong>[7119-95-1]nitropyrazole</strong> (16 g); 1H NMR: (DMSOd6 + CF3CO2H) 8.57 (s, 2H).
Concentrated sulphuric acid (80 ml) was added dropwise to a stirred sample of <strong>[7119-95-1]<strong>[7119-95-1]1-nitropyrazol</strong>e</strong> (20.3 g) that was cooled in an ice-bath. The resultant mixture was stirred for 16 hours and allowed to warm to ambient temperature. The mixture was poured onto ice and stirred for 20 minutes. The resultant solid was isolated and washed with water. The filtrate was neutralised by the addition of potassium carbonate and extracted with diethyl ether. The recovered solid was added to the diethyl ether solution and the resultant solution was washed with a saturated aqueous sodium chloride solution, dried over magnesium sulphate and filtered. Petroleum ether (b.p. 60-80°C) was added to the filtrate which was concentrated by evaporation to a volume of about 50 ml. A precipitate formed which was isolated by filtration. <n="96"/>There was thus obtained 4-<strong>[7119-95-1]nitropyrazole</strong> (16 g); 1H NMR: (DMSOd6 + CF3CO2H) 8.57 (s, 2H).
Concentrated sulphuric acid (80 ml) was added dropwise to a stirred sample of <strong>[7119-95-1]<strong>[7119-95-1]1-nitropyrazol</strong>e</strong> (20.3 g) that was cooled in an ice-bath. The resultant mixture was stirred for 16 hours and allowed to warm to ambient temperature. The mixture was poured onto ice and stirred for 20 minutes. The resultant solid was isolated and washed with water. The filtrate was neutralised by the addition of potassium carbonate and extracted with diethyl ether. The recovered solid was added to the diethyl ether solution and the resultant solution was washed with a saturated aqueous sodium chloride solution, dried over magnesium sulphate and filtered. Petroleum ether (b.p. 60-80° C.) was added to the filtrate which was concentrated by evaporation to a volume of about 50 ml. A precipitate formed which was isolated by filtration. There was thus obtained 4-<strong>[7119-95-1]nitropyrazole</strong> (16 g); 1H NMR: (DMSOd6+CF3CO2H) 8.57 (s, 2H).
0.97 g With sulfuric acid; at 25℃; 1-Nitropyrazole (1 g) was slowly added to a round-bottomed flask containing H2SO4 (98percent, 5 mL) and stirred for 20 h at room temperature. The reaction mixture was slowly transferred to a beaker containing ice with stirring. The solution was extracted with ether. The organic layer was dried with Na2SO4 then evaporated to afford 4-<strong>[7119-95-1]nitropyrazole</strong> as a colorless solid (0.97 g, 96percent). The solid was recrystallized from ether/hexane to get white crystalline compound. m.p. 163?165 °C; FT-IR (KBr, cm?1) 3186 (N?H), 1526 and 1353 cm?1 (NO2). 1H NMR (DMSO-d6) delta: 8.26 (d, 1, 5-H), 6.76 (d, 1, 3-H). EI-MS: m/z 113 (M+·). Anal. Calcd for C3H3N3O2: C, 27.54; H, 3.88; N, 32.42. Found: C, 28.31; H, 3.21; N, 31.38.
The compound may be explosive and should be handled cautiously.Concentrated sulphuric acid (80 ml) was added dropwise to a stirred sample of <strong>[7119-95-1]<strong>[7119-95-1]1-nitropyrazol</strong>e</strong> (20.3 g) that was cooled in an ice-bath. The resultant mixture was stirred for 16 hours and allowed to warm to ambient temperature. The mixture was poured onto ice and stirred for 20 minutes. The resultant solid was isolated and washed with water. The filtrate was neutralised by the addition of potassium carbonate and extracted with diethyl ether. The recovered solid was added to the diethyl ether solution and the resultant solution was washed with a saturated aqueous sodium chloride solution, dried over magnesium sulphate and filtered. Petroleum ether (b.p. 60-80°C) was added to the filtrate which was concentrated by evaporation to a volume of about 50 ml. A precipitate formed which was isolated by filtration. There was thus obtained 4-<strong>[7119-95-1]nitropyrazole</strong> (16 g); 1H NMR Spectrum: (DMSOd6 + CF3CO2H) 8.57 (s, 2H).
Concentrated sulphuric acid (80 ml) was added dropwise to a stirred sample of <strong>[7119-95-1]<strong>[7119-95-1]1-nitropyrazol</strong>e</strong> (20.3 g) that was cooled in an ice-bath. The resultant mixture was stirred for <n="95"/>16 hours and allowed to warm to ambient temperature. The mixture was poured onto ice and stirred for 20 minutes. The resultant solid was isolated and washed with water. The filtrate was neutralised by the addition of potassium carbonate and extracted with diethyl ether. The recovered solid was added to the diethyl ether solution and the resultant solution was washed with a saturated aqueous sodium chloride solution, dried over magnesium sulphate and filtered. Petroleum ether (b.p. 60-80°C) was added to the filtrate which was concentrated by evaporation to a volume of about 50 ml. A precipitate formed which was isolated by filtration. There was thus obtained 4-<strong>[7119-95-1]nitropyrazole</strong> (16 g); 1H NMR Spectrum: (DMSOd6 + CF3CO2H) 8.57 (s, 2H).

  • 2
  • [ 2075-46-9 ]
  • [ 28466-26-4 ]
YieldReaction ConditionsOperation in experiment
100% With palladium 10% on activated carbon; hydrogen; In methanol; at 25℃; under 760.051 Torr; for 12h; Under hydrogen (1 atm), to a solution of 4-nitropyrazole (1.13 g, 10 mmol) in methanol (10 mL) was added 10% Pd-C (0.1 g). The mixture was stirred at 25 C. for 12 hours, and then filtrated, the filtrate was concentrated under reduced pressure to give compound 31-a (860 mg, yield: 100%), which was used directly for the next step without purification.
100% With palladium 10% on activated carbon; hydrogen; In ethanol; at 20℃; 5.0g 4-nitropyrazole was dissolved in 160mL of ethanol and 0.8g of 10% Pd/C was added. The reaction was subjected to hydrogen and reacted overnight at room temperature. TLC was used to monitor reaction completion. By celite was filtered off Pd/C. Ethanol solvent was evaporated to give 3.6g of the pure intermediate 8 as a red solid, quantitative reaction.
99% With palladium 10% on activated carbon; hydrogen; In methanol; for 16h; A suspension of 4-nitro-1H-pyrazole (2.05 g, 18.13 mmol), and Pd/C (10% w/w palladium on activated carbon, 0.96 g, 0.90 mmol) in MeOH (20 mL) was stirred under H2 atmosphere (balloon) for 16 h. The reaction mixture was filtered through Celite, rinsed with MeOH (3x 30 mL) and concentrated, affording 1.50 g of 1H-pyrazol-4- amine (pale pink solid, 99% yield). HPLC-MS (Method H): Ret, 1.16 min; ESI+-MS m/z: 84 (M+1).
95% With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; under 2068.65 Torr; for 3h; Compound Ia (15.0 g, 133 mmol) was added to a suspension of palladium on carbon 10% (7.0 g, 6.65 mmol) in ethanol (100 mL). The mixture was shaken for 3 hours under hydrogen pressure (40 psi) at room temperature. The catalyst was removed by filtration through a pad of Celite and the solvent was evaporated. Compound Ib was obtained as a burgundy oil (10.5 g, 126 mmol, 95%) which was used in the following step without purification; GC/MS: m/z = 83 (100%).
49% With hydrogen;1% Pd/C; In ethanol; under 1034.32 - 1551.49 Torr; A mixture of 4-nitro-l/f-pyrazole (1.13 g, 10 mmol), Pd/C (10%, 57 mg) in ethanol (20 mL) was hydrogenated at 20-30 psi on a parr apparatu overnight. The reaction mixture was filtered through celite, washed with ethanol (10 mL). The filtrate was concentrated to get desired compound 0113-42 (404 mg, 49%) as a brown solid. LC-MS: 84 [M+l]+; 1H-NMR (400 MHz, DMSO-d6) delta 3.11 (br s, 2H), 6.99 (s, 2H), 11.92 (s, IH).
palladium; In ethanol; 4-aminopyrazole (10) The 4-nitropyrazole (9) (15.0 g, 133 mmol) was added to a suspension of palladium on carbon 10% (7.0 g, 6.65 mmol, 5% mmol) in ethanol (100 ml). The mixture was shaken for 3 hours under hydrogen pressure (40 psi) at room temperature. The end of reaction checked by TLC (Ethylacetate/Hexane 1/1, 4-nitropyrazole Rf=0.6, UV active, 4-aminopyrazole Rf 0.1, UV active). The catalyst was removed by filtration through a pad of Celite and the solvent was evaporated. The product (10) was obtained as a burgundy oil (10.5 g, 126 mmol, 95%), which was used in the following step without purification. GC/MS: m/z=83 (100%).
With hydrogen;platinum(IV) oxide; In ethanol; ethyl acetate; under 2280.15 Torr; for 2h; The 4-amino-l/i-pyrazole used as a starting material was prepared as follows :-A mixture of 4-nitro-l/J-pyrazole (0.7 g), platinum oxide (0.05 g), ethyl acetate (5 ml) <n="110"/>and ethanol (15 ml) was stirred under 3 atmospheres pressure of hydrogen for 2 hours. The catalyst was removed by filtration and the filtrate was evaporated. There was thus obtained the required starting material (0.5 g).
With iron; ammonium chloride; In ethanol; water; at 80℃; for 2h; Step2:[00394] To a stirred mixture of iron (1.68g, 30 mmol), ammonium chloride (540mg, 10 mmol), water (2ml_) and ethanol (8ml_) at 800C was added 4-nitro-1 H-pyrazol (1 .13g, lOmmol) in portions. After completion of addition, the mixture was stirred at 800C for additional 2 hours. After cooling to room temperature, the mixture was diluted with ethyl acetate, and the resultant mixture was filtered through a pad of celite. The filtrate was concentrated to afford the crude title compound which was used at next step without further purification. MS (ES) [M+H]+ expected 84.0, found 84.0.
With hydrogen;palladium 10% on activated carbon; In ethanol; under 760.051 Torr; for 22h; Intermediate (1e), 4-nitro-1 H-pyrazole (2.8g, 24.8mmol), was stirred in ethanol (20OmL) and the flask was evacuated and then flushed with nitrogen. Palladium, 10wt. % on activated carbon (300mg, catalytic amount) was added and after two vacuum / H2 cycles to replace the nitrogen inside with hydrogen, the mixture was shaken for 18 hours under ordinary hydrogen pressure (1atm). Palladium, 10wt. % on activated carbon (300mg) was added and after two vacuum / H2 cycles to replace the nitrogen inside with hydrogen, the mixture was shaken for a further 4 hours. The reaction mixture was filtered through celite and the filter cake was washed through with ethanol (2x50ml_). The combined washings and the filtrate were concentrated in vacuo. The residue obtained was triturated with ethyl acetate to yield a light pink solid, 1.48g, 72%. The filtrate subsequently obtained was concentrated in vacuo to yield another batch of sufficiently pure material, 0.54g, 26%, as a dark pink solid.
4-Nitro-1 /-/-pyrazole (Manchester organics; 1.13 g, 9.99 mmol) was dissolved in ethanol (50 ml). This solution was added carefully to 10% palladium on carbon (Aldrich; 102 mg) under a nitrogen atmosphere. The atmosphere was exchanged to hydrogen, and the mixture was stirred vigorously at room temperature under a hydrogen atmosphere. After 45 min, ca. 700 ml of hydrogen had been taken up, and no further hydrogen was taken up over the next 30 min. Stirring was stopped and the atmosphere was exchanged to nitrogen. The solution was filtered through cellite (10 g cartridge) and washed with further ethanol (150 ml). Relevant fractions (as verified by TLC) were combined and concentrated in vacuo to give a red oil. Trituration with DCM gave the title compound (815 mg) as a red solid; 1 H NMR (MeOH-d4, 400 MHz) delta (ppm) 7.20 (2 H, s).
With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; for 1.25h;Inert atmosphere; Intermediate 5: 1 H-Pyrazol-4-amine. 4-Nitro-1H-pyrazole (Manchester organics; 1.13 g, 9.99 mmol) was dissolved in ethanol (50 ml). This solution was added carefully to 10% palladium on carbon (Aldrich; 102 mg) under a nitrogen atmosphere. The atmosphere was exchanged to hydrogen, and the mixture was stirred vigorously at room temperature under a hydrogen atmosphere. After 45 min, ca. 700 ml of hydrogen had been taken up, and no further hydrogen was taken up over the next 30 min. Stirring was stopped and the atmosphere was exchanged to nitrogen. The solution was filtered through cellite (10 g cartridge) and washed with further ethanol (150 ml). Relevant fractions (as verified by TLC) were combined and concentrated in vacuo to give a red oil. Trituration with DCM gave the title compound (815 mg) as a red solid; 1 H NMR (MeOH-d4, 400 MHz) delta (ppm) 7.20 (2 H, s).
With hydrogen;palladium on activated charcoal; In ethanol; at 20℃; for 18h; A -(1H-Pyrazol-4-yl)-5-(m-tolyl)oxazole-4-carboxamide Step 1 : To a round bottom flask, 4-nitro-1 /-/-pyrazole (2.0 g, 17.68 mmol), Pd/C (200 mg, 1.89 mmol) and EtOH (15.0 mL, degassed) was added. The flask was evacuated and backfilled with H2 and the reaction mixture was stirred under H2-atmosphere at rt for 18 h. The reaction mixture was filtered over celite, washed with MeOH and the solvent was removed under reduced pressure to yield 1 H-pyrazol-4-amine as a red oil which was used without further purification. 1 H-NMR (400 MHz, DMSO) delta 3.72 (brs, 2H), 6.99 (s, 2H), 1 1.9 (brs, 1 H).
With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃; for 1h; Synthesis of compound 96.2[00605] A solution of 4-nitro-lH-pyrazole (200 mg, 1.77 mmol, 1.00 equiv) and 10% Palladium on carbon (40 mg) in methanol (5 mL) was degassed with H2 three times and the reaction mixture was stirred for 1 h at room temperature. The catalyst was filtered out and the filtrate was concentrated under vacuum to give 120 mg (crude) of compound 96.2 as a light yellow solid.
3.6 g With palladium 10% on activated carbon; hydrogen; In ethanol; at 20℃; Dissolving 5.0 g of 4-nitropyrazole in 160 mL of ethanol, and then adding 0.8 g of 10 wt% Pd/C to the above solution; Hydrogen was introduced into the reaction solution and allowed to react overnight at room temperature; after the TLC detection reaction was completed, the insoluble matter was filtered off with diatomaceous earth; Evaporation of the ethanol solvent gave pure intermediate 2 as a red solid 3.6 g.

  • 3
  • [ 7119-95-1 ]
  • [ 7664-93-9 ]
  • [ 2075-46-9 ]
  • 4
  • [ 2075-46-9 ]
  • [ 64-19-7 ]
  • zinc dust [ No CAS ]
  • [ 28466-26-4 ]
  • 5
  • [ 2075-46-9 ]
  • [ 10226-29-6 ]
  • [ 1163253-71-1 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate; In acetonitrile; at 80℃; for 2h;Inert atmosphere; 6-(4-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 4-nitro-1H-pyrazole (8.29 g, 64.99 mmol) and Cs2CO3 (31.87 g, 71.49 mmol) in AcCN (75.0 mL) was treated with a solution of 6-bromo-hexan-2-one (12.80 g, 71.49 mmol) in AcCN (58.0 mL). The reaction mixture was stirred at 80 C. for 2 h. Water (270 mL) and EA (400 mL) were added to the cooled reaction mixture. The aq. layer was extracted with EA (400 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)=0.29. LC-MS-conditions 02: tR=0.82 min; [M+H]+=212.18.
  • 6
  • [ 2075-46-9 ]
  • [ 75-03-6 ]
  • [ 876343-24-7 ]
YieldReaction ConditionsOperation in experiment
Procedure A:General Procedure for the Synthesis of 4-Amino-l-N-alkylated-pyrazolesA solution of 4-nitropyrazole (300mg, 2.65mmol), potassium carbonate (2eq) and the alkylating reagent (l .leq) in acetonitrile (lOmL) was heated at 60°C for 18h. After cooling to rt the mixture was diluted with EtOAc and washed with water. The organic phase was collected, dried (MgS04) and concentrated in vacuo. The crude residue was dissolved in methanol (lOmL), palladium on carbon (50mg) was added and the reaction was stirred under a balloon of hydrogen for 18h. The resulting mixture was filtered through Celite and the filtrate concentrated in vacuo to give the desired product. Procedure B:Example 11: 2-((6-( 1 -Ethyl- 1 H-pyrazo 1-4-ylamino)- 1 H-pyrazo lo [3 ,4-d]pyrimidin- 1 -yl) methyl)benzonitrileThe following compound was made according to the procedure in Example 1, using 1-ethyl- lH-pyrazo 1-4-amine. 1 -ethyl- lH-pyrazol-4-amine was prepared by Procedure A using ethyl iodide as alkylating agent: 1H NMR (d6-DMSO) delta 9.94 (s, 1H), 8.94 (s, 1H), 8.10 (s, 2H), 7.91 (dd, 1H), 7.66 (td, 1H), 7.49-7.53 (m, 2H), 7.35-7.37 (m, 1H), 5.76 (s, 2H), 4.11 (q, 2H), 1.35 (t, 3H); LC-MS method B, (ES+) 345.1, RT = 8.58min.
  • 7
  • [ 5344-27-4 ]
  • [ 2075-46-9 ]
  • [ 1383705-77-8 ]
YieldReaction ConditionsOperation in experiment
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃;Inert atmosphere; Step a) Formation of 4-[2-(4-nitro-1 H-pyrazol-1 -yl)ethyl]pyridine D IAD (7.27 m L; 37.2 m mol ; 1 . 1 eq . ) was added slowly i nto a sol ution of 4-(2- hydroxyethyl)pyridine (4.2 g; 34.1 mmol; 1.0 eq.) , 4-nitro-1 H-pyrazole (3.86 g; 34.1 mmol; 1.0 eq.) and triphenylphosphine (9.84 g; 37.5 mmol; 1.1 eq.) in THF (120 mL) maintained under nitrogen at 0C. The reaction mixture was allowed to warm to RT and left O/N. THF was removed under reduced pressure and the crude was purified by flash chromatography on silica (EtOAc:heptane, gradient from 50:50 to 100:0) to afford the title compound in quantitative yield. MS(ESI+): 219.0, (ESI-) 272.1 (purity 92.2%). 1 H NMR (400 Mz, DMSO-d6) delta 8.80 (s, 1 H), 8.44-8.43( m, 2H), 8.24 (s, 1 H), 7.18-7.17 (m, 2H), 4.50-4.48 (t, J = 7.04 Hz, 2H), 3.19-3.17 (t, J = 7.0 Hz, 2H).
  • 8
  • [ 2075-46-9 ]
  • [ 78385-26-9 ]
  • [ 1428574-89-3 ]
YieldReaction ConditionsOperation in experiment
With ammonium formate; In methanol; acetonitrile; Example 42 1-((3-Methyloxetan-3-yl)methyl)-1H-pyrazol-4-amine A mixture of 4-nitropyrazole (1.13 g, 10 mmol) and K2CO3 (3.4 g, 25 mmol) in MeCN (50 mL) was stirred at room temperature for 15 min prior to addition of <strong>[78385-26-9]3-(bromomethyl)-3-methyloxetane</strong> (1.8 g, 11 mmol). The reaction mixture was stirred at room temperature for 18 hr, filtered and the filter cake washed with MeCN. The filtrate was concentrated under reduced pressure and the residue purified by silica gel column chromatography (0-100% EtOAc/isohexane) gradient to afford 1-((3-methyloxetan-3-yl)methyl)-4-nitro-1H-pyrazole as a colorless solid (1.43 g, 73%). A portion of this solid (206 mg, 1.04 mmol) dissolved in MeOH (20 mL) was treated with ammonium formate (260 mg, 4.13 mmol) and 10% palladium on carbon (50 mg). The mixture was heated at 80 C. for 1.5 hr, cooled, filtered through Celite and the filtrate concentrated under reduced pressure to afford 1-((3-methyloxetan-3-yl)methyl)-1H-pyrazol-4-amine as a pale pink gum (160 mg, 92%). 1H NMR (400 MHz, CDCl3) delta 7.15 (s, 1H), 6.97 (s, 1H), 4.66 (d, J=6.1 Hz, 2H), 4.37 (d, J=6.1 Hz, 2H), 4.19 (s, 2H), 2.91 (s, 2H), 1.23 (s, 3H).
  • 9
  • [ 2075-46-9 ]
  • [ 558-42-9 ]
  • [ 1182917-01-6 ]
YieldReaction ConditionsOperation in experiment
78% With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 5h; Synthesis of 2-methyl-1-(4-nitro-1H-pyrazol-1-yl)propan-2-ol A mixture of 4-nitro-1H-pyrazole (1.6 g, 13.9 mmol), 1-chloro-2-methylpropan-2-ol (1.5 g, 13.9 mmol) and Cs2CO3 (9.1 g, 27.8 mmol) in DMF (20 mL) was stirred at 80° C. for 5 h. The reaction mixture was cooled to RT and diluted with EA (200 ml). The organic phase was washed by water (50 mL) and brine (50 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 2-methyl-1-(4-nitro-1H-pyrazol-1-yl)propan-2-ol as a yellow oil (2.0 g, 78percent), which was used for the next step without further purification. MS (ES+) C7H11N3O3 requires: 185, found: 186 [M+H]+.
64% With caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 14h; To a strried solution of 4-nitro-1H-pyrazole 12 (5.0 g, 44.0 mmol) and 1- chloro-2-methylpropan-2-ol 12a (9.5 g, 88.0 mmol) in DMF (60 mL), cesium carbonate (26 g, 88.0 mmol) was charged at room temperature. The reaction contents were heated at 100°C for 14 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (120 mL) and washed with water (2 x 100 mL). The organic layer was dried (Na2SO4), filtered and concentrated to give 2-methyl-i -(4-nitro- I H-pyrazol- 1 -yl)propan2-ol 18 (5.2 g, 64percent yield). ?HNMR (400 MHz, DMSO-d6): oe 8.6 (s, 1H), 8.25 (s, 1H),4.83 (s, 1H), 4.09 (s, 2H), 1.08 (s, 6H).
  • 10
  • [ 2075-46-9 ]
  • [ 476014-76-3 ]
  • 4-(4-nitro-1H-pyrazol-1-yl)piperidin-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 27℃; for 16.16h; A solution of DIAD (5.3 g, 26.4 mmol) in dry THF (20 mL) was added to a solution of (<strong>[476014-76-3]4-hydroxypiperidin-2-one</strong> 41 (2.20 g, 19.4 mmol), 4-nitro-1H-pyrazole (2.0 g, 17.6 mmol) and triphenyiphosphine (6.9 g, 26.4 mmol) in dry THF (80 mL) drop-wise at 0°C over a period of 10 mm. The mixture was then stirred at room temperature for 16h. Solvents evaporated under reduced pressure to obtain a crude solid, which was purified by flash chromatography on silica gel using ethyl acetate as eluent to obtain 3 4-(4-nitro- 1H-pyrazol-1-yl)piperidin-2-one 42 (1.8 g, 48percent yield) as a white solid. ?H NMR (400 MHz, DMSO-d6): 8.96 (s, 1H), 8.31 (s, 1H), 7.71 (s, 1H), 4.83-4.79 (m, 1H), 3.25-3.15 (m, 2H), 2.69-2.67 (m, 2H), 2.20-2.17 (m, 1H), 2.13-2.06 (m, 1H).
  • 11
  • [ 2075-46-9 ]
  • [ 28466-26-4 ]
  • [ 63680-90-0 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; triethylsilane; 5% palladium on Al2O3; In ethanol; water; at 15℃; for 72h;Inert atmosphere; Example 1 3-chloro-1H-pyrazol-4-amine hydrochloride (1a) A 1000-mL, multi-neck cylindrical jacketed reactor, fitted with a mechanical stirrer, temperature probe and nitrogen (N2) inlet, was charged with 4-nitropyrazole (50.0 g, 429 mmol) and palladium on alumina (5 wt %, 2.5 g). Ethanol (150 mL) was added, followed by a slow addition of concentrated hydrochloric acid (37 wt %, 180 mL). The reaction was cooled to 15 C., and triethylsilane (171 mL, 1072 mmol) was added slowly via addition funnel over 1 hour, while maintaining the internal temperature at 15 C. The reaction was stirred at 15 C. for 72 hours, after which the reaction mixture was filtered through a Celite pad and the pad was rinsed with warm ethanol (40 C., 2*100 mL). The combined filtrates were separated and the aqueous layer (bottom layer) was concentrated to ?100 mL. Acetonitrile (200 mL) was added and the resulting suspension was concentrated to ?100 mL. Acetonitrile (200 mL) was added and the resulting suspension was concentrated to ?100 mL. Acetonitrile (200 mL) was added and the resulting suspension was stirred at 20 C. for 1 hour and filtered. The filter cake was rinsed with acetonitrile (2*100 mL) and dried under vacuum at 20 C. to afford a white solid (?10:1 mixture of 1a and 1H-pyrazole-4-amine, 65.5 g, 99%): 1H NMR (400 MHz, DMSO-d6) delta 10.52 (bs, 3H), 8.03 (s, 1H) EIMS m/z 117 ([M]+).
With hydrogenchloride; triethylsilane; 5% palladium on Al2O3; In ethanol; water; at 15℃; for 73h;Inert atmosphere; Example 1 3-chloro-1H-pyrazol-4-amine hydrochloride (1a) [0019] nitrogen (N2) inlet, was charged with 4-nitropyrazole (50.0 g, 429 mmol) and palladium on alumina (5 weight %, 2.5 g). Ethanol (150 mL) was added, followed by a slow addition of concentrated hydrochloric acid (37%, 180 mL). The reaction was cooled to 15 C., and triethylsilane (171 mL, 1072 mmol) was added slowly via addition funnel over 1 hour, while maintaining the internal temperature at 15 C. The reaction was stirred at 15 C. for 72 hours, after which the reaction mixture was filtered through a Celite pad and the pad was rinsed with warm ethanol (40 C., 2×100 mL). The combined filtrates were separated and the aqueous layer (bottom layer) was concentrated to 100 mL. Acetonitrile (200 mL) was added and the resulting suspension was concentrated to 100 mL. Acetonitrile (200 mL) was added and the resulting suspension was concentrated to 100 mL. Acetonitrile (200 mL) was added and the resulting suspension was stirred at 20 C. for 1 hour and filtered. The filter cake was rinsed with acetonitrile (2×100 mL) and dried under vacuum at 20 C. to afford a white solid (10:1 mixture of 1a and 1H-pyrazol-4-amine, 65.5 g, 99%): 1H NMR (400 MHz, DMSO-d6) delta 10.52 (bs, 3H), 8.03 (s, 1H) EIMS: m/z 117.
With hydrogenchloride; triethylsilane; Pd/Al2O3; In ethanol; water; at 15℃; for 73h; Example 1 3-Chloro-1H-pyrazol-4-amine hydrochloride (1a) A 1000-mL, multi-neck cylindrical jacketed reactor, fitted with a mechanical stirrer, temperature probe and nitrogen (N2) inlet, was charged with 4-nitropyrazole (50.0 g, 429 mmol) and palladium on alumina (5 wt %, 2.5 g). Ethanol (150 mL) was added, followed by a slow addition of concentrated hydrochloric acid (37 wt %, 180 mL). The reaction was cooled to 15 C., and triethylsilane (171 mL, 1072 mmol) was added slowly via addition funnel over 1 hour, while maintaining the internal temperature at 15 C. The reaction was stirred at 15 C. for 72 hours, after which the reaction mixture was filtered through a Celite pad and the pad was rinsed with warm ethanol (40 C., 2*100 mL). The combined filtrates were separated and the aqueous layer (bottom layer) was concentrated to ?100 mL. Acetonitrile (200 mL) was added and the resulting suspension was concentrated to ?100 mL. Acetonitrile (200 mL) was added and the resulting suspension was concentrated to ?100 mL. Acetonitrile (200 mL) was added and the resulting suspension was stirred at 20 C. for 1 hour and filtered. The filter cake was rinsed with acetonitrile (2*100 mL) and dried under vacuum at 20 C. to afford a white solid (?10:1 mixture of 1a and 1H-pyrazol-4-amine, 65.5 g, 99%): 1H NMR (400 MHz, DMSO-d6) delta 10.52 (bs, 3H), 8.03 (s, 1H); EIMS m/z 117 ([M]+).
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