[ CAS No. 24807-55-4 ] {[proInfo.proName]}

Name: 24807-55-4|3-Nitro-1H-1,2,4-triazole|98%
Brand: Ambeed
SKU: A118742
Price: 9.0 USD
Availability: InStock
Rating: 95 (22 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

DV 2D 3D

3d Animation Molecule Structure of 24807-55-4

Structure of 24807-55-4 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 24807-55-4 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 24807-55-4 ]

SDS Specification

Alternatived Products of [ 24807-55-4 ]

Product Details of [ 24807-55-4 ]

CAS No. :	24807-55-4	MDL No. :	MFCD00009749
Formula :	C₂H₂N₄O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KUEFXPHXHHANKS-UHFFFAOYSA-N
M.W :	114.06	Pubchem ID :	90614
Synonyms :

Calculated chemistry of [ 24807-55-4 ]

Physicochemical Properties

Num. heavy atoms :	8
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	4.0
Num. H-bond donors :	1.0
Molar Refractivity :	25.2
TPSA :	87.39 Å²

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) :	-7.23 cm/s

Lipophilicity

Log Po/w (iLOGP) :	-0.41
Log Po/w (XLOGP3) :	-0.33
Log Po/w (WLOGP) :	-0.29
Log Po/w (MLOGP) :	-0.51
Log Po/w (SILICOS-IT) :	-0.74
Consensus Log Po/w :	-0.46

Druglikeness

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

Water Solubility

Log S (ESOL) :	-0.74
Solubility :	21.0 mg/ml ; 0.184 mol/l
Class :	Very soluble
Log S (Ali) :	-1.04
Solubility :	10.3 mg/ml ; 0.0904 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.19
Solubility :	74.0 mg/ml ; 0.649 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.37

Safety of [ 24807-55-4 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 24807-55-4 ]

* 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.

Upstream synthesis route of [ 24807-55-4 ]
Downstream synthetic route of [ 24807-55-4 ]

[ 24807-55-4 ] Synthesis Path-Upstream 1~15

1
[ 24807-55-4 ]
[ 6818-99-1 ]

Reference： [1] Journal of Medicinal Chemistry, 1996, vol. 39, # 15, p. 3019 - 3029

2
[ 24807-55-4 ]
[ 7343-33-1 ]

Reference： [1] Journal of Medicinal Chemistry, 2004, vol. 47, # 19, p. 4645 - 4648

3
[ 61-82-5 ]
[ 24807-55-4 ]

Yield	Reaction Conditions	Operation in experiment
68%	Stage #1: With sodium nitrite In water for 0.166667 h; Cooling with ice Stage #2: With nitric acid In water at 20℃;	A 2.0 l, three-necked, round-bottomed flask equipped withan overhead mechanical stirrer, a 100 ml pressure-equalizing addition funnel, and a glassstopperwas charged with 3-amino-1,2,4-triazole (26.3 g, 0.297 mol) and an aqueoussodium nitrite solution (100.0 g, 1.45 mol in 150 ml water) in an efficient fumehood.The suspension was cooled in an ice-water bath and the mechanical stirrer was started.After 10 min of stirring, the light suspension was treated dropwise with conc. nitric acid(85 ml) via the addition funnel over a period of 2.5–3.0 h (foaming).45 After completeaddition of nitric acid, the ice-water bath was removed and the yellow suspension wasstirred for additional 1.0 h at room temperature until foaming stopped.46 The crude productwas collected and the yellow solid filter cake was dried overnight under oil pump vacuum,to give a yellow solid (47 g). The crude product was dissolved in boiling methanol(300 ml) for 30 min, and then filtered hot using house vacuum. The methanol filtratewas allowed to cool to rt. and then placed overnight in a freezer at −15C whereupon3-nitro-1,2,4-triazole crystallized as a light yellow solid, which was collected, washed withice-cold methanol, and dried overnight at 1.9 mmHg to afford 21–23 g (62percent–68percent) ofthe title compound, mp. 208C–211C (lit.37 208–210).1H NMR (300 MHz, DMSO-d6):δ 8.86 (s, 1H); 13C NMR (75 MHz, DMSO-d6): δ 163.1, 146.3; IR (solid): 3162, 2861,2776, 2730. The purity of the product (97percent) established by RP-HPLC, tR = 2.01 min(254 nm).

Reference： [1] Organic Process Research and Development, 2014, vol. 18, # 7, p. 886 - 890
[2] Tetrahedron, 1980, vol. 36, # 20-21, p. 3075 - 3085
[3] Organic Preparations and Procedures International, 2014, vol. 46, # 3, p. 267 - 271
[4] Russian Journal of Organic Chemistry, 2014, vol. 50, # 5, p. 742 - 746[5] Zh. Org. Khim., 2014, vol. 50, # 5, p. 752 - 756,5

4
[ 61-82-5 ]
[ 7664-93-9 ]
[ 24807-55-4 ]

Yield	Reaction Conditions	Operation in experiment
57%	With urea; sodium nitrite In water; acetic acid	II. Preparation of 3-nitro-1,2,4-triazole A solution of 16.8 g (0.2 mole) of 3-amino-1,2,4-triazole in 160 ml of glacial acetic acid is added to a solution of -6 g (0.23 mole) of sodium nitrite in 70 ml of concentrated suIphuric acId at a temperature of 0 to -5° C. After 5 minutes, there is a dropwise addition of 50 ml of water at a temperature not exceeding 0°. The solution obtained is then added to 200 ml of 10percent sodium nitrite at a temperature of 45 to 50° C. This is followed by heating at 45° C. for 1 hour, acidification of the solution with 6 ml of H₂ SO₄ to make the nitrogen oxides disappear and treatment with 12 g of urea to destroy the dissolved nitrogen oxides. The solution is then extracted with ethyl acetate. After eliminating the ethyl acetate by evaporation, the product is recrystallized in methanol and in this way 13 g of 3-nitro-1,2,4triazole are obtained. Its melting point is 210° C. and the yield is 57percent.

Reference： [1] Patent: US4958027, 1990, A,

5
[ 61-82-5 ]
[ 24807-55-4 ]

Reference： [1] Russian Journal of Organic Chemistry, 1997, vol. 33, # 8, p. 1125 - 1132
[2] Russian Journal of Organic Chemistry, 1997, vol. 33, # 12, p. 1803 - 1804

6
[ 36899-13-5 ]
[ 24807-55-4 ]

Reference： [1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1989, vol. 38, # 3.2, p. 662 - 663[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1989, # 3, p. 736 - 738

7
[ 81911-06-0 ]
[ 24807-55-4 ]

Reference： [1] Journal of Organic Chemistry USSR (English Translation), 1982, vol. 18, p. 587 - 588[2] Zhurnal Organicheskoi Khimii, 1982, vol. 18, # 2, p. 676 - 677

8
[ 81606-82-8 ]
[ 24807-55-4 ]

Reference： [1] Journal of Organic Chemistry USSR (English Translation), 1982, vol. 18, p. 587 - 588[2] Zhurnal Organicheskoi Khimii, 1982, vol. 18, # 2, p. 676 - 677

9
[ 70965-24-1 ]
[ 24807-55-4 ]

Reference： [1] Journal of Organic Chemistry USSR (English Translation), 1982, vol. 18, p. 587 - 588[2] Zhurnal Organicheskoi Khimii, 1982, vol. 18, # 2, p. 676 - 677

10
[ 26621-45-4 ]
[ 24807-55-4 ]

Reference： [1] Journal of Organic Chemistry USSR (English Translation), 1982, vol. 18, p. 587 - 588[2] Zhurnal Organicheskoi Khimii, 1982, vol. 18, # 2, p. 676 - 677

11
[ 36899-13-5 ]
[ 71-43-2 ]
[ 117082-53-8 ]
[ 24807-55-4 ]

12
[ 133157-99-0 ]
[ 4114-36-7 ]
[ 24807-55-4 ]
[ 26621-29-4 ]
[ 26621-45-4 ]

Reference： [1] Russian Journal of Organic Chemistry, 1994, vol. 30, # 9, p. 1470 - 1475[2] Zhurnal Organicheskoi Khimii, 1994, vol. 30, # 9, p. 1398 - 1403

13
[ 126401-88-5 ]
[ 71-43-2 ]
[ 117082-53-8 ]
[ 24807-55-4 ]

Reference： [1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1988, vol. 37, p. 1458 - 1461[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1988, # 7, p. 1643 - 1646
[3] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1988, vol. 37, p. 1458 - 1461[4] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1988, # 7, p. 1643 - 1646

14
[ 74205-83-7 ]
[ 24807-55-4 ]

Reference： [1] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1980, vol. 16, # 2, p. 189 - 194[2] Khimiya Geterotsiklicheskikh Soedinenii, 1980, vol. 16, # 2, p. 251 - 256

15
[ 773-64-8 ]
[ 24807-55-4 ]
[ 74257-00-4 ]

Yield	Reaction Conditions	Operation in experiment
48%	With triethylamine In 1,4-dioxane for 1.5 h; Cooling with ice	An oven dried 1.0 l round-bottomedflask containing a magnetic stir bar was equipped with a Claisen adapter. 3-Nitro-1,2,4-triazole (19.5 g, 0.171 mol), dry dioxane (200 ml) and triethylamine (1.0 equiv., 17.3 g,0.171 mol) was transferred to the reaction flask and the solution was cooled in an ice-bathwith magnetic stirring.47 The Claisen adapter was fitted with a 200 ml pressure-equalizingaddition funnel, containing a dioxane solution (150 ml) of mesitylenesulfonyl chloride(37.4 g, 0.171 mol). The solution of mesitylenesulfonyl chloride was added dropwise overa period of approx. 0.5 h and the final suspension was stirred for an additional 1 h andthen warmed to rt. After removal of the precipitated Et3N·HCl by filtration, the filtratewas concentrated in vacuo to give a yellow solid, which was dissolved in dichloromethane(150 ml) and the solution was washed with water (150 ml).48 The organic layer was driedover anhydrous Na2SO4 and evaporated in vacuo to give a yellow solid. Recrystallizationfrom boiling toluene (20–30 ml) followed by washing with ice-cold toluene and dryingovernight at 1.9 mmHg, provided 24–25 g (46percent–48percent) of the title compound as light yellow solid,49 mp. 131C–133C (lit.37 130C–132C). Rf = 0.23 (20percent hexane in CH2Cl2, UV);1H NMR (300 MHz, CDCl3): δ 8.84 (s, 1H), 7.07 (s, 2H), 2.69 (s, 6H), 2.34 (s, 3H);13C NMR (75 MHz, CDCl3): δ 162.9, 147.5, 145.2, 142.5, 133.0, 127.9, 23.2, 21.3; IR(solid): 3126, 2983, 2947, 1597.Anal. Calcd. for C11H12N4O4S: C, 44.59; H, 4.08; N, 18.91. Found: C, 44.69; H,3.88; N, 18.72. The purity of the product (96percent) established by RP-HPLC, tR = 8.41 min(254 nm).

Reference： [1] Organic Preparations and Procedures International, 2014, vol. 46, # 3, p. 267 - 271
[2] Tetrahedron Letters, 1986, vol. 27, # 45, p. 5529 - 5532

[ 24807-55-4 ] Synthesis Path-Downstream 1~88

1
[ 61-82-5 ]
[ 24807-55-4 ]

Yield	Reaction Conditions	Operation in experiment
68%		A 2.0 l, three-necked, round-bottomed flask equipped withan overhead mechanical stirrer, a 100 ml pressure-equalizing addition funnel, and a glassstopperwas charged with 3-amino-1,2,4-triazole (26.3 g, 0.297 mol) and an aqueoussodium nitrite solution (100.0 g, 1.45 mol in 150 ml water) in an efficient fumehood.The suspension was cooled in an ice-water bath and the mechanical stirrer was started.After 10 min of stirring, the light suspension was treated dropwise with conc. nitric acid(85 ml) via the addition funnel over a period of 2.5-3.0 h (foaming).45 After completeaddition of nitric acid, the ice-water bath was removed and the yellow suspension wasstirred for additional 1.0 h at room temperature until foaming stopped.46 The crude productwas collected and the yellow solid filter cake was dried overnight under oil pump vacuum,to give a yellow solid (47 g). The crude product was dissolved in boiling methanol(300 ml) for 30 min, and then filtered hot using house vacuum. The methanol filtratewas allowed to cool to rt. and then placed overnight in a freezer at -15C whereupon3-nitro-1,2,4-triazole crystallized as a light yellow solid, which was collected, washed withice-cold methanol, and dried overnight at 1.9 mmHg to afford 21-23 g (62%-68%) ofthe title compound, mp. 208C-211C (lit.37 208-210).1H NMR (300 MHz, DMSO-d6):delta 8.86 (s, 1H); 13C NMR (75 MHz, DMSO-d6): delta 163.1, 146.3; IR (solid): 3162, 2861,2776, 2730. The purity of the product (97%) established by RP-HPLC, tR = 2.01 min(254 nm).

Reference： [1]Organic Process Research and Development,2014,vol. 18,p. 886 - 890
[2]Tetrahedron,1980,vol. 36,p. 3075 - 3085
[3]Organic Preparations and Procedures International,2014,vol. 46,p. 267 - 271
[4]Russian Journal of Organic Chemistry,2014,vol. 50,p. 742 - 746
Zh. Org. Khim.,2014,vol. 50,p. 752 - 756,5

2
[ 18704-37-5 ]
[ 24807-55-4 ]
[ 77244-88-3 ]

Reference： [1]Liebigs Annalen der Chemie,1982,p. 745 - 753
[2]Chemistry Letters,1982,p. 197 - 200

3
[ 773-64-8 ]
[ 24807-55-4 ]
[ 74257-00-4 ]

Yield	Reaction Conditions	Operation in experiment
48%	With triethylamine; In 1,4-dioxane; for 1.5h;Cooling with ice;	An oven dried 1.0 l round-bottomedflask containing a magnetic stir bar was equipped with a Claisen adapter. 3-Nitro-1,2,4-triazole (19.5 g, 0.171 mol), dry dioxane (200 ml) and triethylamine (1.0 equiv., 17.3 g,0.171 mol) was transferred to the reaction flask and the solution was cooled in an ice-bathwith magnetic stirring.47 The Claisen adapter was fitted with a 200 ml pressure-equalizingaddition funnel, containing a dioxane solution (150 ml) of mesitylenesulfonyl chloride(37.4 g, 0.171 mol). The solution of mesitylenesulfonyl chloride was added dropwise overa period of approx. 0.5 h and the final suspension was stirred for an additional 1 h andthen warmed to rt. After removal of the precipitated Et3N·HCl by filtration, the filtratewas concentrated in vacuo to give a yellow solid, which was dissolved in dichloromethane(150 ml) and the solution was washed with water (150 ml).48 The organic layer was driedover anhydrous Na2SO4 and evaporated in vacuo to give a yellow solid. Recrystallizationfrom boiling toluene (20?30 ml) followed by washing with ice-cold toluene and dryingovernight at 1.9 mmHg, provided 24?25 g (46percent?48percent) of the title compound as light yellow solid,49 mp. 131C?133C (lit.37 130C?132C). Rf = 0.23 (20percent hexane in CH2Cl2, UV);1H NMR (300 MHz, CDCl3): delta 8.84 (s, 1H), 7.07 (s, 2H), 2.69 (s, 6H), 2.34 (s, 3H);13C NMR (75 MHz, CDCl3): delta 162.9, 147.5, 145.2, 142.5, 133.0, 127.9, 23.2, 21.3; IR(solid): 3126, 2983, 2947, 1597.Anal. Calcd. for C11H12N4O4S: C, 44.59; H, 4.08; N, 18.91. Found: C, 44.69; H,3.88; N, 18.72. The purity of the product (96percent) established by RP-HPLC, tR = 8.41 min(254 nm).

Reference： [1]Organic Preparations and Procedures International,2014,vol. 46,p. 267 - 271
[2]Tetrahedron Letters,1986,vol. 27,p. 5529 - 5532

4
[ 24807-55-4 ]
[ 598-31-2 ]
[ 60728-89-4 ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium hydroxide In water; acetone at 20℃; for 16h;
71%	With potassium hydroxide; tetrabutylammomium bromide In water; 1,2-dichloro-ethane at 20℃; for 1.5h;

Reference： [1]Semenov, V. V.; Ugrak, B. I.; Shevelev, S. A.; Kanishchev, M. I.; Baryshnikov, A. T.; Fainzil'berg, A. A. [Bulletin of the Academy of Sciences of the USSR Division of Chemical Science, 1990, vol. 39, # 8.2, p. 1658 - 1666][Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1990, # 8, p. 1827 - 1837]
[2]Samet; Yamskov; Kachala; Semenov [Russian Chemical Bulletin, 1999, vol. 48, # 3, p. 552 - 556]

5
[ 24807-55-4 ]
[ 26621-29-4 ]
[ 26621-31-8 ]
[ 26621-45-4 ]

Yield	Reaction Conditions	Operation in experiment
1: 9% 2: 3% 3: 69%	In toluene for 1h; Heating;

Reference： [1]Middleton; Monney; Parrick [Synthesis, 1984, vol. NO. 9, # 9, p. 740 - 743]

6
[ 26621-45-4 ]
[ 24807-55-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium <i>tert</i>-butylate In tetrahydrofuran at 20 - 25℃; for 2h; DMSO as a solvent; Yield given;

Reference： [1]Terpigorev, A. N.; Shcherbinin, M. B.; Bazanov, A. G.; Tselinskii, I. V. [Journal of Organic Chemistry USSR (English Translation), 1982, vol. 18, p. 587 - 588][Zhurnal Organicheskoi Khimii, 1982, vol. 18, # 2, p. 676 - 677]

7
[ 24807-55-4 ]
[ 3181-38-2 ]
[ 99824-71-2 ]

Reference： [1]Nucleosides and Nucleotides,1996,vol. 15,p. 749 - 769
[2]Tetrahedron Letters,1995,vol. 36,p. 91 - 94

8
[ 24807-55-4 ]
[ 4105-38-8 ]
[ 76887-37-1 ]

Yield	Reaction Conditions	Operation in experiment
94%	With diphenyl hydrogen phosphate; p-toluenesulfonyl chloride In pyridine for 36h; Ambient temperature;
94%	With diphenyl hydrogen phosphate; p-toluenesulfonyl chloride In pyridine for 36h; Ambient temperature;

Reference： [1]Kamaike, Kazuo; Takahashi, Mihoko; Utsugi, Kazuyuki; Tomizuka, Kazue; Ishido, Yoshiharu [Tetrahedron Letters, 1995, vol. 36, # 1, p. 91 - 94]
[2]Kamaike; Takahashi; Utsugi; Tomizuka; Okazaki; Tamada; Kinoshita; Masuda; Ishido [Nucleosides and Nucleotides, 1996, vol. 15, # 1-3, p. 749 - 769]

9
[ 133157-99-0 ]
[ 4114-36-7 ]
[ 24807-55-4 ]
[ 26621-29-4 ]
[ 26621-45-4 ]

Yield	Reaction Conditions	Operation in experiment
1: 1 % Chromat. 2: 1 % Chromat. 3: 1 % Chromat. 4: 75 % Chromat.	With methyl iodide at 3 - 21℃; for 1.5h; Further byproducts given. Title compound not separated from byproducts;

Reference： [1]Pevzner, M. S.; Kurenkov, A. A.; Trubitsin, A. E. [Russian Journal of Organic Chemistry, 1994, vol. 30, # 9, p. 1470 - 1475][Zhurnal Organicheskoi Khimii, 1994, vol. 30, # 9, p. 1398 - 1403]

10
[ 24807-55-4 ]
[ 6818-99-1 ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 3019 - 3029

11
[ 91229-86-6 ]
[ 24807-55-4 ]
[ 219999-31-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry,1998,vol. 6,p. 2139 - 2149

12
[ 24415-66-5 ]
[ 24807-55-4 ]
5-methyl-7-(3-nitro-[1,2,4]triazol-1-yl)-[1,2,4]triazolo[1,5-<i>a</i>]pyrimidine [ No CAS ]

Reference： [1]Russian Journal of Organic Chemistry,2000,vol. 36,p. 866 - 872

13
[ 24807-55-4 ]
[ 7343-33-1 ]

Reference： [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 4645 - 4648

14
[ 14098-24-9 ]
[ 24807-55-4 ]
2,3,5,6,8,9,11,12,14,15-decahydro-1,4,7,10,13,16-benzohexaoxacyclooctadecine, 1:2 complex with 3-nitro-1,2,4-triazole [ No CAS ]

Reference： [1]Russian Journal of General Chemistry,2004,vol. 74,p. 803 - 805

15
[ 24807-55-4 ]
[ 77-78-1 ]
1,4-dimethyl-3-nitro-1,2,4-triazolium methyl sulfate [ No CAS ]
[ 26621-29-4 ]
[ 26621-31-8 ]
[ 26621-45-4 ]

Yield	Reaction Conditions	Operation in experiment
	at 78 - 80℃; for 2.5h;

Reference： [1]Sukhanov; Sakovich; Sukhanova; Lukin [Chemistry of Heterocyclic Compounds, 2005, vol. 41, # 8, p. 994 - 998]

16
[ 24807-55-4 ]
[ 77-78-1 ]
[ 26621-29-4 ]
[ 26621-45-4 ]

Yield	Reaction Conditions	Operation in experiment
33%	With lithium hydroxide In ethanol at 75℃;
	With sodium hydroxide In ethanol at 20 - 25℃; for 72h;

Reference： [1]Calbo, Joaquín; Weston, Claire E.; White, Andrew J. P.; Rzepa, Henry S.; Contreras-García, Julia; Fuchter, Matthew J. [Journal of the American Chemical Society, 2017, vol. 139, # 3, p. 1261 - 1274]
[2]Sukhanov; Lukin [Chemistry of Heterocyclic Compounds, 2005, vol. 41, # 7, p. 861 - 865]

17
[ 24807-55-4 ]
[ 74-88-4 ]
[ 26621-29-4 ]
[ 26621-45-4 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium hydroxide In ethanol at 20 - 25℃; for 200h;

Reference： [1]Sukhanov; Lukin [Chemistry of Heterocyclic Compounds, 2005, vol. 41, # 7, p. 861 - 865]

18
chloro (N,N-diisopropylamino)-methoxyphosphine [ No CAS ]
[ 24807-55-4 ]
methoxy-N,N-diisopropylamino(3-nitro-1,2,4-triazolyl)phosphine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With triethylamine; In tetrahydrofuran; dichloromethane;	EXAMPLE 6 Synthesis of Methoxy-N,N-diisopropylamino(3-nitro-1,2,4-triazolyl)phosphine (2) To a stirred solution of <strong>[24807-55-4]3-nitro-1,2,4-triazole</strong> (0.69 g, 6.07 mmol) and triethylamine (2.82 mL, 2.05 g, 20.2 mmol) in THF (10 mL) and CH2Cl2 (20 mL) was added dropwise chloro(N,N-diisopropylamino)methoxyphosphine (1.0 g, 5.06 mmol) at room temperature. The mixture was stirred overnight at room temperature. The reaction mixture was filtered to removed the resulting salt, and the solvent was removed under reduced pressure to give the crude product as a pale brown oil (1.24 g, 89%). 31P NMR (CDCl3) delta 135.9.

Reference： [1]Patent: US6340749,2002,B1

19
[ 124482-92-4 ]
[ 24807-55-4 ]
2-Cyanoethoxy(N,N-diisopropylamino)(3-nitro-1,2,4-triazolyl)phosphine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With triethylamine; In tetrahydrofuran;	EXAMPLE 5 Synthesis of 2-Cyanoethoxy(N,N-diisopropylamino)(3-nitro-1,2,4-triazolyl)phosphine (1) To a stirred solution of <strong>[24807-55-4]3-nitro-1,2,4-triazole</strong> (9.64 g, 84.50 mmol) and triethylamine (14.0 mL, 10.26 g, 101.4 mmol) in THF (200 mL) was added dropwise chloro-2-cyanoethoxy-N,N-diisopropylaminophosphine (20.0 g, 84.50 mmol) at room temperature. The mixture was stirred overnight at room temperature. The reaction mixture was filtered to remove the resulting salt, and the solvent was removed under reduced pressure to give the crude product as a pale brown oil (24.9 g, 95%). After standing at room temperature, the oil becomes a pale yellow wax-like solid. 1H NMR (CDCl3 delta 8.39 (s, 1H), 4.09 (m, 2H), 3.51 (m, 2H), 2.81 (m, 2H), 1.19 (d, J=6.0 Hz, 6H), 1.07 (d, J=9.0 Hz, 6H). 31P NMR (CDCl3) delta 133.9.

Reference： [1]Patent: US6340749,2002,B1

20
[ 86030-44-6 ]
[ 24807-55-4 ]
methoxy(3-nitro-1,2,4-triazolyl)pyrrolidinophosphine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With triethylamine; In tetrahydrofuran; dichloromethane;	EXAMPLE 7 Synthesis of Methoxy(3-nitro-1,2,4-triazolyl)pyrrolidinophosphine (3) To a stirred solution of <strong>[24807-55-4]3-nitro-1,2,4-triazole</strong> (2.70 g, 23.71 mmol) and triethylamine (11.0 mL, 8.0 g, 79.0 mmol) in THF (40 mL) and CH2Cl2 (20 mL) was added dropwise chloro(methoxy)pyrrolidinophosphine (3.31 g, 19.76 mmol) at room temperature. The mixture was stirred overnight at room temperature. The reaction mixture was filtered to remove the resulting salt, and the solvent was removed under reduced pressure to give the crude product as a pale yellow oil (3.97 g, 82%). 31P NMR (CDCl3) delta 132.9.

Reference： [1]Patent: US6340749,2002,B1

21
chloro(N,N-dimethylamino)methoxyphosphine [ No CAS ]
[ 24807-55-4 ]
N,N-Dimethylamino(Methoxy)(3-nitro-1,2,4-triazolyl)phosphine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With triethylamine; In tetrahydrofuran; dichloromethane;	EXAMPLE 8 Synthesis of N,N-Dimethylamino(Methoxy)(3-nitro-1,2,4-triazolyl)phosphine (4) To a stirred solution of <strong>[24807-55-4]3-nitro-1,2,4-triazole</strong> (2.86 g, 25.1 mmol) and triethylamine (14.0 mL, 10.2 g, 101 mmol) in THF (40 mL) was added dropwise Chloro(N,N-dimethylamino)methoxyphosphine (3.55 g, 25.1 mmol) in CH2Cl2 (10 mL) at room temperature. The mixture was stirred for 3 h at room temperature. The reaction mixture was filtered to remove the resulting salt, and the solvent was removed under reduced pressure to give the crude product as a yellow oil (4.56 g, 83%) 31P NMR (CDCl3) delta 134.9.

Reference： [1]Patent: US6340749,2002,B1

22
[ 73742-45-7 ]
[ 24807-55-4 ]
5-chloro-6-(3-nitro-1,2,4-triazol-1-yl-methyl)uracil [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With potassium hydroxide;	Example 4 Synthesis of 5-chloro-6-(3-nitro-1,2,4-triazol-1-yl-methyl)uracil (Compound23) To a solution of 0.88 g of <strong>[24807-55-4]3-nitro-1,2,4-triazole</strong> in a 1N aqueous solution of KOH (10 ml), 0.50 g of 5-chloro-6-chloromethyluracil was added, followed by heating at 80 C. for 2.5 hours under stirring. The reaction mixture was neutralized with 6N hydrochloric acid. A precipitate was collected by filtration and then washed with water and methanol, whereby 510 mg of the title compound were obtained (yield: 73%).
73%	With potassium hydroxide;	Example 4 Synthesis of 5-chloro-6-(3-nitro-1,2,4-triazol-1-yl-methyl)uracil (Compound 23) To a solution of 0.88 g of <strong>[24807-55-4]3-nitro-1,2,4-triazole</strong> in a 1 N aqueous solution of KOH (10 ml), 0.50 g of 5-chloro-6-chloromethyluracil was added, followed by heating at 80 C. for 2.5 hours under stirring. The reaction mixture was neutralized with 6 N hydrochloric acid. A precipitate was collected by filtration and then washed with water and methanol, whereby 510 mg of the title compound were obtained (yield: 73%).

Reference： [1]Patent: US5744475,1998,A
[2]Patent: US6255314,2001,B1

23
[ 61-82-5 ]
[ 7664-93-9 ]
[ 24807-55-4 ]

Yield	Reaction Conditions	Operation in experiment
57%	With urea; sodium nitrite; In water; acetic acid;	II. Preparation of 3-nitro-1,2,4-triazole A solution of 16.8 g (0.2 mole) of 3-amino-1,2,4-triazole in 160 ml of glacial acetic acid is added to a solution of -6 g (0.23 mole) of sodium nitrite in 70 ml of concentrated suIphuric acId at a temperature of 0 to -5 C. After 5 minutes, there is a dropwise addition of 50 ml of water at a temperature not exceeding 0. The solution obtained is then added to 200 ml of 10% sodium nitrite at a temperature of 45 to 50 C. This is followed by heating at 45 C. for 1 hour, acidification of the solution with 6 ml of H2 SO4 to make the nitrogen oxides disappear and treatment with 12 g of urea to destroy the dissolved nitrogen oxides. The solution is then extracted with ethyl acetate. After eliminating the ethyl acetate by evaporation, the product is recrystallized in methanol and in this way 13 g of 3-nitro-1,2,4triazole are obtained. Its melting point is 210 C. and the yield is 57%.

Reference： [1]Patent: US4958027,1990,A

24
[ 28920-43-6 ]
[ 24807-55-4 ]
[ 1001067-08-8 ]

Reference： [1]Organic Letters,2007,vol. 9,p. 5231 - 5234
[2]Heterocycles,2008,vol. 76,p. 1301 - 1312

25
[ 20160-60-5 ]
[ 24807-55-4 ]
[ 1001067-09-9 ]

Reference： [1]Organic Letters,2007,vol. 9,p. 5231 - 5234
[2]Heterocycles,2008,vol. 76,p. 1301 - 1312

26
[ 501-53-1 ]
[ 24807-55-4 ]
[ 1001067-06-6 ]

Reference： [1]Organic Letters,2007,vol. 9,p. 5231 - 5234
[2]Heterocycles,2008,vol. 76,p. 1301 - 1312

27
[ 24807-55-4 ]
[ 17341-93-4 ]
[ 1001067-07-7 ]

Reference： [1]Organic Letters,2007,vol. 9,p. 5231 - 5234
[2]Heterocycles,2008,vol. 76,p. 1301 - 1312

28
[ 76-83-5 ]
[ 24807-55-4 ]
[ 935760-23-9 ]

Yield	Reaction Conditions	Operation in experiment
93%	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃; for 15h;	Reference Example 33 3-nitro-1-(triphenylmethyl)-1H-1,2,4-triazole A solution of <strong>[24807-55-4]3-nitro-1H-1,2,4-triazole</strong> (1.00 g, 8.77 mmol), trityl chloride (4.89 g, 17.5 mmol) and diisopropylethylamine (3.05 mL, 17.5 mmol) in THF (50 mL) was stirred at room temperature for 15 hr. The mixture was concentrated under reduced pressure, and the residue was extracted with ethyl acetate and water. The organic layer was washed with saturated brine, dried over sodium sulfate, and concentrated. The residue was purified by silica gel column chromatography (15 - 30% ethyl acetate/hexane) to give the title compound as a white powder (2.90 g, 93%). 1H-NMR (300MHz, CDCl3) delta: 7.08-7.17 (6H, m), 7.33-7.47 (9H, m), 8.04 (1H, s).

Reference： [1]Patent: EP1953148,2008,A1 .Location in patent: Page/Page column 119
[2]Journal of Medicinal Chemistry,2017,vol. 60,p. 608 - 626

29
[ 1550-35-2 ]
[ 24807-55-4 ]
[ 885028-66-0 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 3; Preparation of [5-(3-nitro-1,2,4-triazolyl)-2-difluoromethylphenyl]2,2,2-trifluoroethyl sulfide (Compound No. 11 of the present invention); (1) Synthesis of 4-(3-nitro-1,2,4-triazolyl)-2-fluorobenzaldehyde; 10 ml of a N,N-dimethylformamide solution of 3.4 g of <strong>[24807-55-4]3-nitro-1,2,4-triazole</strong> was added dropwise to a suspension of 1.2 g (60%) of sodium hydride and 50 ml of N,N-dimethylformamide under cooling with ice. After generation of hydrogen stopped, 4.3 g of 2,4-difluorobenzaldehyde was added, followed by stirring at 70C for 3 hours. The mixture was concentrated under reduced pressure, 200 ml of water was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained crude crystals were washed with diisopropyl ether to obtain 1.6 g of 4-(3-nitro-1,2,4-triazolyl)-2-fluorobenzaldehyde.

Reference： [1]Patent: EP1803712,2007,A1 .Location in patent: Page/Page column 38

30
[ 24807-55-4 ]
[ 174313-65-6 ]
[ 1189797-83-8 ]

Yield	Reaction Conditions	Operation in experiment
89%		Iodine (16.5 g, 65.1 mmol) was added to a suspension of compound 5a (8.03 g, 29.6 mmol), <strong>[24807-55-4]3-nitro-1H-1,2,4-triazole</strong> (11.8 g, 103.6 mmol), triphenylphosphine (18.1 g, 69.1 mmol) in 630 mL of toluene. The reaction mixture was rapidly heated to 95 C for 15 min after which 25 mL of N,N-diisopropylethylamine was added and the mixture was stirred for another 50 min. The reaction was cooled to room temperature and concentrated under reduced pressure. The crude product was precipitated from ethyl alcohol, to give 6 as a yellow solid (9.67 g, 89%). Mp: 204 C, 1H NMR (400 MHz, DMSO-d6) delta 9.87 (1H, s), 8.97 (1H, dd, J = 2.2 and 0.3 Hz), 8.18 (1H, dd, J = 9.0 and 2.2 Hz), 7.88 (1H, dd, J = 9.0 and 0.3 Hz), 2.70 (3H, s); 13C NMR (100 MHz, DMSO-d6) delta 167.0, 163.2, 152.3, 151.1, 148.2, 139.1, 129.1, 127.9, 120.5, 114.3, 14.0; HRMS (FAB+): C11H8N6O2BrS calcd: 366.9613 [M+H]; found 366.9615.
89%		Iodine (16.5 g, 65.1 mmol) was added to a suspension of compound 5a (8.03 g, 29.6 mmol), 3- 20 nitro-1W-1,2,4-triazole (11.8 g, 103.6 mmol), triphenylphosphine (18.1 g, 69.1 mmol) in 630 mL of toluene. The reaction mixture was rapidly heated to 95 0C for 15 minutes after which 25 mL of lambda/,lambda/-diisopropylethylamine was added and the mixture was stirred for another 50 minutes. The reaction was cooled to room temperature and concentrated under reduced pressure. The crude product was precipitated from ethanol, to give 6 as a yellow solid (9.67 g, 89%). mp: 204 25 0C, . . . . . .1H NMR (400 MHz, DMSO-d6) delta 9.87 (1H1 s), 8.97 (1H, dd, J = 2.2 and 0.3Hz), 8.18 (1H, dd, J = 9.0 and 2.2 Hz), 7-88 (1 H , dd, J = 9.0 and 0.3Hz), 2.70 (3H, s); 13C NMR (100 MHz1 DMSO- d6) delta 167.0, 163^2, 152.3, 151.1 , 148.2, 139.1 , 129.1 , 127.9; 120.5, 114.3, 14.0; HRMS (FAB+): C11H8N6O2BrS calcd; 366.9613 [M+H]; found 366.9615. 30

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 111 - 121
[2]Patent: WO2009/123537,2009,A1 .Location in patent: Page/Page column 18

31
[ 24807-55-4 ]
[ 123436-06-6 ]
[ 1206464-86-9 ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In water; acetonitrile; at 80℃; for 0.25h;Sealed reaction vial;	-[18F]Fluoro-3-(3-nitro-lH-l,2,4-triazoI-l-yl)propan-2-ol (38); hi a sealed reaction vial, purified 2-[18F](fluoromethyl)oxirane in MeCN/H20 (7:3) solution (0.5 mL) was added to 2-imidazole (5 mg) and caesium carbonate (5 mg) and heated to 80C for 15 minutes. Analysis by HPLC (Zorbax SB, C 18, 250 x 4.6 mm, MeCN/H20 (1 :9) 1 mL/min) gave a retention time of 7.22 minutes. Comparison with a cold reference HPLC trace confirmed the product to be the successfully labelled target compound. Analysis by radio-TLC (EtOAc) indicated 50% RCY.

Reference： [1]Patent: WO2010/7363,2010,A2 .Location in patent: Page/Page column 83

32
[ 1501-84-4 ]
[ 24807-55-4 ]
[ 1207947-28-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2010,vol. 18,p. 839 - 848

33
[ 31984-10-8 ]
[ 24807-55-4 ]
[ 1092852-24-8 ]

Reference： [1]Chemical Biology and Drug Design,2010,vol. 75,p. 68 - 90

34
[ 4026-28-2 ]
[ 24807-55-4 ]
[ 1333220-46-4 ]

Yield	Reaction Conditions	Operation in experiment
78%		General procedure: To a suspension of nitroimidazole/nitrotriazole (2 mmol) in anhydrous DMF (5 mL) maintained over an ice-bath, NaH (60% suspension in mineral oil, 1 mol equiv) was added and stirred. After 15 min, compound 10 (1 mmol) was added and stirred at 100 C overnight. After the completion of the reaction, the solvent was evaporated off under reduced pressure. The crude product was taken up in CH2Cl2 and was extracted with water. The organic layer was dried over anhydrous sodium sulfate and was concentrated under reduced pressure. The crude product was subjected to column chromatography to get pure 11a-f.

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 4725 - 4732

35
[ 70969-90-3 ]
[ 24807-55-4 ]
[ 1333220-29-3 ]

Yield	Reaction Conditions	Operation in experiment
60%		General procedure: To a suspension of the nitromidazoles/nitrotriazole (2.5 mmol) in anhydrous DMF (5 mL) maintained over an ice-bath, NaH (60% suspension in mineral oil, 1 mol equiv) was added and the mixture was stirred. After 15 min 6-O-(2,3-epoxypropyl)-1:2,3:4-di-O-isopropylidene-alpha-d-galactopyranose (6, 1 mmol) was added and the stirring was continued. After the completion of the reaction, a few drops of methanol were added. The solvent was evaporated off under reduced pressure and the crude product was purified by column chromatography (except in the case of compound 7f which was directly converted to 8f, the corresponding palmitoyl ester.

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 4725 - 4732

36
[ 24807-55-4 ]
[ 1423-26-3 ]
[ 1354721-91-7 ]

Yield	Reaction Conditions	Operation in experiment
49%	With pyridine; copper diacetate; In dichloromethane; at 30℃;Molecular sieve;	Intermediate 2a: 3-nitro- 1 -(3 -(trifluoromethyl phenyiy 1 H- 1 ,2,4-triazole. Into a 250- mL round bottom flask, was placed a solution of 3-nitro-lH-l,2,4-triazole (2 g, 17.54 mmol, 1.00 equiv) in dichloromethane (100 mL), 3-(trifluoromethyl)phenylboronic acid (6.66 g, 35.05 mmol, 2.00 equiv), Cu(OAc)2 (4.79 g, 26.32 mmol, 1.50 equiv), pyridine (2.77 g, 35.06 mmol, 2.00 equiv), and molecular sieves (5.2 g). The resulting solution was stirred overnight at 30C. The solids were filtered out. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1 :20-1:10) to give 2.2 g (49%) of product as a white solid.

Reference： [1]Patent: WO2012/6473,2012,A1 .Location in patent: Page/Page column 51

37
[ 76513-69-4 ]
[ 24807-55-4 ]
[ 1361311-19-4 ]

Yield	Reaction Conditions	Operation in experiment
54%		Step A: To a solution of <strong>[24807-55-4]3-nitro-1H-1,2,4-triazole</strong> (0.5 g, 4.38 mmol) in anhydrous DMF (20 mL) was added potassium carbonate (0.67 g, 4.82 mmol), and the mixture was stirred at rt for 10 min and then (2-(chloromethoxy)ethyl)trimethylsilane (0.73 g, 4.38 mmol) was added. The mixture was stirred at rt for 1 h and then partitioned between EtOAc (100 mL) and water (100 mL). The aqueous layer was separated and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with brine (2×100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography eluting with 0-50% EtOAc/hexanes to afford colorless crystals, which were triturated with diethyl ether to afford a single isomer of SEM-protected <strong>[24807-55-4]3-nitro-1,2,4-triazole</strong> (SEM=(2-(trimethylsilyl)ethoxy)methyl)) as a white solid (0.58 g, 54%). 1H NMR (300 MHz, DMSO-d6) delta 9.09 (s, 1H), 5.69 (s, 2H), 3.58-3.75 (m, 2H), 0.84-0.99 (m, 2H), 0.00 (s, 9H).
42%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 3h;	Synthesis of 3-nitro-l-((2-(trimethylsilyl)ethoxy)methyl)-lH-l,2,4-triazole (2) (0309) [0187] To a solution of 3-nitro-lH-l,2,4-triazole (1, 1.0 g, 8.76 mmol) in dimethylformamide (10 mL), potassium carbonate (3.62 g, 26.2 mmol) and 2-(trimethylsilyl)ethoxymethyl chloride (1.6 g, 9.64 mmol) were added. The reaction mixture was stirred at room temperature for 3 h. After completion, ice water (25 mL) was added and the reaction was extracted with ethyl acetate (100 mL). The organic layer was washed with saturated ammonium chloride solution (25 mL), brine (25 mL), dried over anhydrous sodium sulfate, filtered and concentrated to afford 3-nitro- l-((2-(trimethylsilyl)ethoxy)methyl)-lH-l,2,4-triazole (2) as a white solid. Yield: 0.91 g, 42%; MS (ESI) m/z 303.16[M+AcO"]".

Reference： [1]Patent: US2012/53174,2012,A1 .Location in patent: Page/Page column 56-57
[2]Patent: WO2017/87808,2017,A1 .Location in patent: Paragraph 0187

38
[ 24807-55-4 ]
[ 218301-22-5 ]
5-formyl-2-(3-nitro-1H-1,2,4-triazol-1-yl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 14h;	Example 92Preparation of 5-formyl-2-(3-nitro-1H-1,2,4-triazol-1-yl)benzonitrile (DI52); To a stiffing solution of 2-fluoro-5-formylbenzonitrile (0.5 g, 3.3 mmol) in DMF (25 mL) were added K2CO3 (0.68 g, 4.95 mmol) and 3-nitro-1,2,4 triazole (0.45 g, 4.2 mmol) and the resultant reaction mixture was stirred at RT for 14 h. After completion of reaction (TLC), the reaction mixture was diluted with water and extracted with EtOAc. The combined EtOAc layer was washed with water and brine then dried over Na2SO4 and concentrated under reduced pressure to afforded the title compound as a pale yellow solid (0.36 g, 45%): mp 170-172 C.; 1H NMR (300 MHz, DMSO-d6) delta 10.12 (s, 1H), 9.61 (s, 1H), 8.69 (s, 1H), 8.45 (d, J=9.3 Hz, 1H), 8.23 (d, J=9.3 Hz, 1H); ESIMS m/z 242.3 ([M-H]-); IR (thin film) 2238, 1705, 1551, 1314 cm-1.
45%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 14h;	Example 92: Preparation of 5-Formyl-2-(3-nitro-lH-l,2,4-triazol-l-yl)benzonitrile (DI52) To a stirring solution of 2-fluoro-5-formylbenzonitrile (0.5 g, 3.3 mmol) in DMF (25 mL) were added K2CO3 (0.68 g, 4.95 mmol) and 3-nitro-l,2,4 triazole (0.45 g, 4.2 mmol) and the resultant reaction mixture was stirred at RT for 14 h. After completion of reaction (TLC), the reaction mixture was diluted with water and extracted with EtOAc. The combined EtOAc layer was washed with water and brine then dried over Na2S04 and concentrated under reduced pressure to afforded the title compound as a pale yellow solid (0.36 g, 45%): mp 170-172 C; ]H NMR (300 MHz, DMSO-d6) delta 10.12 (s, IH), 9.61 (s, IH), 8.69 (s, IH), 8.45 (d, J = 9.3 Hz, IH), 8.23 (d, J = 9.3 Hz, IH); ESIMS m/z 242.3 ([M-H]"); IR (thin film) 2238, 1705, 1551, 1314 cm"1.
45%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 14h;	To a stiffing solution of 2-fluoro-5-formylbenzonitrile (0.5 g, 3.3 mmol) in DMF (25 mL) were added K2CO3 (0.68 g, 4.95 mmol) and 3-nitro-1,2,4 triazole (0.45 g, 4.2 mmol) and the resultant reaction mixture was stirred at ambient temperature for 14 h. After completion of reaction (TLC), the reaction mixture was diluted with water and extracted with EtOAc. The combined EtOAc layer was washed with water and brine then dried over Na2SO4 and concentrated under reduced pressure to afforded the title compound as a pale yellow solid (0.36 g, 45%): mp 170-172 C.; 1H NMR (300 MHz, DMSO-d6) delta 10.12 (s, 1H), 9.61 (s, 1H), 8.69 (s, 1H), 8.45 (d, J=9.3 Hz, 1H), 8.23 (d, J=9.3 Hz, 1H); ESIMS m/z 242.3 ([M-H]-); IR (thin film) 2238, 1705, 1551, 1314 cm-1.

45%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 14h;	To a stiffing solution of 2-fluoro-5-formylbenzonitrile (0.5 g, 3.3 mmol) in DMF (25 mL) were added K2CO3 (0.68 g, 4.95 mmol) and 3-nitro-1,2,4 triazole (0.45 g, 4.2 mmol) and the resultant reaction mixture was stirred at RT for 14 h. After completion of reaction (TLC), the reaction mixture was diluted with water and extracted with EtOAc. The combined EtOAc layer was washed with water and brine then dried over Na2SO4 and concentrated under reduced pressure to afforded the title compound as a pale yellow solid (0.36 g, 45%): mp 170-172 C.; 1H NMR (300 MHz, DMSO-d6) delta 10.12 (s, 1H), 9.61 (s, 1H), 8.69 (s, 1H), 8.45 (d, J=9.3 Hz, 1H), 8.23 (d, J=9.3 Hz, 1H); ESIMS m/z 242.3 ([M-H]-); IR (thin film) 2238, 1705, 1551, 1314 cm-1.
45%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 14h;	Example 92 Preparation of 5-Formyl-2-(3-nitro-1H-1,2,4-triazol-1-yl)benzonitrile (DI52) To a stirring solution of 2-fluoro-5-formylbenzonitrile (0.5 g, 3.3 mmol) in DMF (25 mL) were added K2CO3 (0.68 g, 4.95 mmol) and 3-nitro-1,2,4 triazole (0.45 g, 4.2 mmol) and the resultant reaction mixture was stirred at ambient temperature for 14 h. After completion of reaction (TLC), the reaction mixture was diluted with water and extracted with EtOAc. The combined EtOAc layer was washed with water and brine then dried over Na2SO4 and concentrated under reduced pressure to afforded the title compound as a pale yellow solid (0.36 g, 45%): mp 170-172 C.; 1H NMR (300 MHz, DMSO-d6) delta 10.12 (s, 1H), 9.61 (s, 1H), 8.69 (s, 1H), 8.45 (d, J=9.3 Hz, 1H), 8.23 (d, J=9.3 Hz, 1H); ESIMS m/z 242.3 ([M-H]-); IR (thin film) 2238, 1705, 1551, 1314 cm-1.
	With potassium carbonate; In N,N-dimethyl-formamide;	Example 92 Preparation of 5-Formyl-2-(3-nitro-1H-1,2,4-triazol-1-yl)benzonitrile (DI52) To a stirring solution of 2-fluoro-5-formylbenzonitrile (0.5 g, 3.3 mmol) in DMF (25 mL) were added K2CO3 (0.68 g, 4.95 mmol) and 3-nitro-1,2,4 triazole (0.45 g, 4.2 mmol) and the resultant reaction mixture was stirred at ambient temperature for 14 h. After completion of reaction (TLC), the reaction mixture was diluted with water and extracted with EtOAc. The combined EtOAc layer was washed with water and brine then dried over Na2SO4 and concentrated under reduced pressure to afforded the title compound as a pale yellow solid (0.36 g, 45%): mp 170-172 C.; 1H NMR (300 MHz, DMSO-d6) delta 10.12 (s, 1H), 9.61 (s, 1H), 8.69 (s, 1H), 8.45 (d, J=9.3 Hz, 1H), 8.23 (d, J=9.3 Hz, 1H); ESIMS m/z 242.3 ([M-H]-); IR (thin film) 2238, 1705, 1551, 1314 cm-1.

Reference： [1]Patent: US2012/329649,2012,A1 .Location in patent: Page/Page column 72-73
[2]Patent: WO2014/100163,2014,A1 .Location in patent: Page/Page column 132
[3]Patent: US2014/171308,2014,A1 .Location in patent: Paragraph 0665-0666
[4]Patent: US2014/171312,2014,A1 .Location in patent: Paragraph 0830; 0831
[5]Patent: US9211280,2015,B2 .Location in patent: Page/Page column 134
[6]Patent: US2014/171314,2014,A1 .Location in patent: Page/Page column

39
[ 24807-55-4 ]
[ 98-80-6 ]
[ 117082-53-8 ]

Yield	Reaction Conditions	Operation in experiment
65%	With pyridine; copper diacetate; at 20℃; for 168h;Molecular sieve;	A mixture of <strong>[24807-55-4]3-nitro-1H-1,2,4-triazole</strong> (25 g, 219.2 mmol), copper(II) acetate (60 g, 330 mmol), 4 A molecular sieves (9.2 g, 45.51 mmol), pyridine (18 mL, 220 mmol) and phenylboronic acid (approximately 53.80 g, 441.2 mmol) was stirred at room temperature open to air for 7 days. The crude reaction mixture was filtered through Celite, washed with dichloromethane and ethyl acetate. The filtrate was concentrated to dryness under reduced pressure. The crude was a cyan colored solid. The crude material was slurried with 1L of ethyl acetate and filtered through a silica plug. The silica plug was then washed with 2L of ethyl acetate. The filtrate was concentrated to dryness under reduced pressure and the residue was triturated with -150 mL of diethyl ether to yield 3 -nitro-1 -phenyl- 1,2,4-triazole (27 g, 65%). NMR (300 MHz, CDCh) delta 8.64 (d, J = 1.6 Hz, 1H), 7.88 - 7.66 (m, 2H), 7.59 (dtd, J = 14.7, 8.0, 7.4, 4.1 Hz, 3H) ppm. ESI-MS m/z calc. 190.04907, found 191.07 (M+l)+; Retention time: 0.72 minutes.
50%	With oxygen; sodium hydroxide; copper dichloride; In methanol; for 16h;Reflux;	General procedure: A mixture of 1.6 mmol of C-nitro-NH-azole (1a-e), 2.6 mmol of arylboronic acid (2a-n), 1.6 mmol of sodium hydroxide, 0.2 mmol of CuCl2 and methanol (15 mL) was refluxed while air was bubbled through the reaction mixture. After completion of the reaction, determined on the basis of TLC analysis, the solvent was removed under reduced pressure using a rotary evaporator. The obtained crude product was purified by silica gel column chromatography with 5:95 v/v MeOH/CHCl3 as an eluent to give corresponding N-aryl-C-nitroazole. The product was crystallized from methanol/water.
24%	With pyridine; copper diacetate; In dichloromethane; at 20℃; for 240h;	[00473j <strong>[24807-55-4]3-nitro-1H-1,2,4-triazole</strong> (20g, l75mmol) and phenylboronic acid (43g, 35Ommol) were suspended in 2.4 L of DCM and pyridine (28.4mL, 27.8g, 35lmmol) was added followed by copper (II) acetate (32g, 175 mmol). The blue coloured suspension was stined at room temperature for 10 days open to the air. The reaction was pulled through a pad of diatomaceous earth and the filter cake washed with DCM, MeOH, and finally DCM. The filtrates were combined and concentrated to a viscous residue which was partitioned between EtOAc and iN HC1. The organic phase was washed with water and brine, dried over Na2 S04 and the solvent removed under reduced pressure. The crude material was purified on 800 grams of 5i02 eluting with 0-25% Ethyl Acetate in DCM. The combined pure fractions were concentrated to dryness to yield 3-nitro-1-phenyl-1,2,4-triazole, RG-la (16g, 24%). ?H NMR (300 MHz, Acetone-d6) oe 9.31 (s, 1H), 7.96 (d, J = 7.9 Hz, 2H), 7.67 (dd, J = 10.3, 5.0 Hz, 2H), 7.61 - 7.46 (m, 1H) ppm. ESI-MS m/z calc. 190.05, found 191.0 (M+1)+; Retention time: 0.73 minutes.

Reference： [1]Patent: WO2018/106646,2018,A1 .Location in patent: Paragraph 00379; 00380
[2]Beilstein Journal of Organic Chemistry,2013,vol. 9,p. 1517 - 1525
[3]Patent: WO2016/197009,2016,A1 .Location in patent: Paragraph 00473

40
[ 29683-23-6 ]
[ 24807-55-4 ]
C₇H₁₀N₄O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; at 20℃;	General procedure: Two mmol amine (2a-c), 0.28 g (2.4 mmol) tetrahydro-2H-thiopyran-4-alcohol, 0.63 g (2.4 mmol) triphenylphosphine, 0.42 g (2.4 mmol) DEAD and 10 mL THF were added to a dry three-neck flask (50 mL), and the reaction mixture was stirred at room temperature overnight. It was then concentrated under reduced pressure and 0.66 g (12 mmol) iron powder and 20 mL 95 % ethanol were added to the stirred solution, and the reaction mixture was heated at 50 C. Next, 0.5 mL concentrated hydrochloric acid was added dropwise, and the reaction mixture was heated to reflux for 4 h, cooled, and filtered. The solution from reduced pressure condensation was washed with 30 mL (1 M) hydrochloric acid and ethyl acetate (10 mL x 2), and the water phase was adjusted to pH >9 with sodium hydroxide and extracted with ethyl acetate (10 mL x 2) . The combined extract was dried and evaporated to dryness, to provide a yellow solid. The solid was recrystallized from CH3CH2OH/H2O with the addition of activated carbon.

Reference： [1]Research on Chemical Intermediates,2015,vol. 41,p. 3793 - 3801

41
[ 24807-55-4 ]
[ 60121-78-0 ]
1-(4-(4-chlorophenyl)piperazin-1-yl)-2-(3-nitro-1H-1,2,4-triazol-1-yl)ethanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%		General procedure: The potassium salt of <strong>[24807-55-4]3-nitro-1,2,4-triazole</strong> or 2-nitroimidazole(1 eq) was formed in CH3CN (6-10 mL), by refluxing with KOH (1.2 eq) for 30 min. To this suspension 1a-l (1.1 eq) was added andthe reaction mixture was refluxed under a nitrogen atmosphere for 9 h. If chloride 1 was an oil, it was added in CH3CN solution. Thereaction mixture was checked by TLC for completion of the reaction and the solvent was evaporated. The residue was redissolved in ethyl acetate or acetone and the inorganic salts were filtered away.Upon preparative TLC (usually on silica gel; ethyl acetate petroleum ether), the desired product was obtained as a powder. Purity was checked also by HPLC and it was 95%. 4.1.3.1. 1-(4-(4-Chlorophenyl)piperazin-1-yl)-2-(3-nitro-1H-1,2,4- triazol-1-yl)ethanone (2). Yellow powder (77%): mp 226 o C (dec);1H NMR (400 MHz, CD3COCD3 a drop of DMSO-6d) d: 8.66 (s, 1H),7.26 (d, J 8.8 Hz, 2H), 7.03 (d, J 8.8 Hz, 2H), 5.59 (s, 2H), 3.80 (t, J 5.2 Hz, 2H), 3.73 (t, J 5.2 Hz, 2H), 3.35 (t, J 5.2 Hz, 2H), 3.23 (t, J 5.2 Hz, 2H). HRESIMS calcd for C14H16ClN6O3 andC14H15ClN6NaO3 m/z [M H] and [M Na] 351.0967 and 373.0786, 375.0762 found 351.0964 and 373.0786, 375.0752.