[ CAS No. 1594-57-6 ] {[proInfo.proName]}

Name: 1594-57-6|N-Hydroxyisonicotinimidamide|98%
Brand: Ambeed
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2D 3D

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Quality Control of [ 1594-57-6 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 1594-57-6 ]

Product Details of [ 1594-57-6 ]

CAS No. :	1594-57-6	MDL No. :	MFCD00125873
Formula :	C₆H₇N₃O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	-
M.W :	137.14	Pubchem ID :	-
Synonyms :

Calculated chemistry of [ 1594-57-6 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	3.0
Molar Refractivity :	36.32
TPSA :	69.0 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) :	-7.33 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.65
Log Po/w (XLOGP3) :	-0.27
Log Po/w (WLOGP) :	0.39
Log Po/w (MLOGP) :	-0.06
Log Po/w (SILICOS-IT) :	0.1
Consensus Log Po/w :	0.16

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-0.83
Solubility :	20.2 mg/ml ; 0.147 mol/l
Class :	Very soluble
Log S (Ali) :	-0.72
Solubility :	26.1 mg/ml ; 0.191 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.56
Solubility :	3.73 mg/ml ; 0.0272 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	3.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.54

Safety of [ 1594-57-6 ]

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

Application In Synthesis of [ 1594-57-6 ]

* 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 [ 1594-57-6 ]

[ 1594-57-6 ] Synthesis Path-Downstream 1~88

1
[ 100-48-1 ]
[ 1594-57-6 ]

Yield	Reaction Conditions	Operation in experiment
85%	With hydroxylamine hydrochloride; sodium hydrogencarbonate; In ethanol; for 6h;Reflux;	General procedure: To a stirred suspension of corresponding nitrile and hydroxylamine hydrochloride (1.5 equiv.) in EtOH (10 mL per gram of nitrile) a NaHCO3 (1.5 equiv.) was added. The reaction mixture was stirred under reflux for a 6 h. After the reaction had completed, the reaction mixture was concentrated under reduced pressure, and the residue was diluted with cold water (200 mL). The resulting precipitate was filtered off and washed with cold water (50 mL). N'-Hydroxyisonicotinimidamide (AM-1). Compound was synthesized by following GP1 starting from isonicotinonitrile (10 g, 0.1 mol) in 85% (11.6 g) yield
83%	With hydroxylamine hydrochloride; sodium hydrogencarbonate; In ethanol; water; for 3h;Reflux;	General procedure: 4-Methylbenzonitrile 42b (940 mg, 8.0 mmol) in EtOH (30 mL) wasadded to NH2OH.HCl (3.34 g, 48 mmol) and NaHCO3 (2.54 g,24 mmol) in water (30 mL) and the mixture was boiled under reflux for 3 h. TheEtOH was evaporated and the residue was poured into water. The precipitatewas collected, washed (water) and dried to give 44b (940 mg, 78%) as awhite powder.
76.7%	With hydroxylamine; In ethanol; water; for 18h;Heating / reflux;	Reaction of 4-pyridinecarbonitrile to give the product N'-hydroxyisonicotinimidamide: Pyridinecarbonitrile (1 g, 9.6 mmol) and hydroxylamine (50% in water, 0.88 cm3, 14.4 mmol, 1.5 eq) in EtOH (10 cm3) were stirred under reflux for 18 hours, after which the volatiles were removed under reduced pressure and the residue was recrystallised from EtOH to give the product N'-hydroxyisonicotinimidamide (1.01 g, 76.7%) as a solid, mp 203-205 C.

	With hydroxylamine hydrochloride; sodium carbonate; In water;	Reference Example 2: Synthesis of 4-(5-amino-1,2,4-oxadiazol-3-yl)pyridine. 17.1 g of 4-cyanopyridine, 70 ml of water, 11.4 g of hydroxylamine hydrochloride and 8.7 g of Na2CO3 were stirred in an autoclave for 8 hours with heating at 70C and, after cooling, the resulting reaction mixture was mixed with 60 ml of water, heated again and then spontaneously cooled to obtain 20.8 g of isonicotinamidoxime.
	With hydroxylamine hydrochloride; sodium hydrogencarbonate; In ethanol; water; for 6h;Reflux;	General procedure: Sodium bicarbonate (5.88 g, 70 mmol) was added in portionsto a solution of 4.79 g hydroxylamine hydrochloride(70 mmol) in 20 cm3 of water. A solution of aryl nitriles(35 mmol) in 50 cm3 of ethanol was then added, and themixture stirred under reflux for 6 h. The precipitate formedwas filtered off and purified by crystallization from ethanol.Melting points of compounds 1b-1f were in agreementwith the literature values [23, 25-28].
	With hydroxylamine hydrochloride; sodium hydroxide; In ethanol; water; for 8h;Reflux;	General procedure: All solvents and reagents were obtained from commercialsources. All synthesized compounds were purified by chromatography and analyzed by IR, HRMS, and NMR. Purity of synthesizedcompounds was verified prior to biological tests by chromatographic analyses and NMR (see supplementary material) and in allthe cases purity was higher than 95%. IR spectra have been registered (in Nujol) with a Shimadzu FTIR-8300 spectrophotometer;melting points have been determined on a Reichart-Thermovarhotstage Kofler and are uncorrected. NMR spectra have beenregistered on a Bruker AVANCE DMX 300 using CDCl3 and DMSO assolvent. HRMS spectra were recorded by analyzing a 50 ppm solution of the compound in a 6540 UHD Accurate-Mass Q-TOF LC/MS(Agilent Technologies) equipped with a Dual AJS ESI source. GC-MSspectra have been registered by using either an Agilent 7890B/7000C GC-MS-TQ or a GC-MS Shimadzu QP-2010 Instrument. Flashchromatography was performed by using silica gel (Merck,0.040e0.063 mm) and mixtures of ethyl acetate and petroleumether (fraction boiling in the range of 40e60 C) in various ratios. 3-Methyl-benzamidoxime [31], 2-picolin-amidoxime [32],isonicotin-amidoxime [33], nicotin-amidoxime [33], and benzamidoxime [34] were synthesized as reported. Generally, an acqueous solution of hydroxylamine was prepared by mixingNH2OH*HCl (36 mmol) and NaOH (36 mmol) in water (20 mL). Thehydroxylamine solution was then added to an alcoholic solution ofthe corresponding nitrile (30 mmol) dissolved in ethanol (100 mL)in a 250 mL round bottomed flask. The mixture was refluxed for 8 h.The solvent was then removed under vacuum and 100 mL waterwere added to the residue. The amidoxime was filtered as a whitesolid and re-crystallized from ethanol.
	With hydroxylamine monohydrate; In ethanol; at 90℃; for 1h;Sealed tube;	General procedure: In a pressurized sealed vial, aqueous hydroxylamine 50% w/w (4equiv) was added to a stirred solution of the appropriate carbonitrile(1 equiv) in absolute ethanol. The resulting mixture washeated at 90 C for 1 h. The solvent was then evaporated to drynessproviding the desired amidoxime quantitatively, which was usedwithout further purification.
	With hydroxylamine hydrochloride; sodium carbonate; In ethanol; water; at 20℃; for 17.1667h;	The compounds 4-pyridyl carbonitrile (commercially available) (25g, 240.13mmoles), hydroxylamine hydrochloride (61.24g, 881.28mmoles) and sodium carbonate (43.77g, 413.02mmoles) were dissolved in a solution of water (125ml) and ethanol (375ml). The reaction mixture was then stirred for 10 minutes at room temperature followed by refluxing for 17 hrs. The resulting reaction mixture was cooled to room temperature and diluted with ice-cold water. The precipitate thus obtained were collected by filtration, washed with water and dried under vacuum to furnish the title compound.Yield = 30g.
	With hydroxylamine hydrochloride; sodium acetate; In ethanol; water; at 50 - 60℃; for 8h;	General procedure: 0.01mol nitrile dissolved in 10 ml ethanol. After that, 0.011 mol hydroxylamine hydrochloride, 10 ml water and 1.23g sodium acetate was added as followed, stirred in room temperature for 0.5 h then refluxed in 50-60 for 8 h. The ethanol was mostly evaporated in vacuum and then the aqueous residue was extracted with CH2Cl2 three times. The combined organic layer was dried over MgSO4 and evaporated to dryness to afford the desired product.

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 6942 - 6990
[2]Journal of Medicinal Chemistry,2001,vol. 44,p. 1560 - 1563
[3]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 3661 - 3666
[4]Tetrahedron Letters,2019,vol. 60
[5]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 3013 - 3032
[6]Journal of Heterocyclic Chemistry,2009,vol. 46,p. 1271 - 1279
[7]Patent: US2009/112024,2009,A1 .Location in patent: Page/Page column 29
[8]Journal of Materials Chemistry C,2019,vol. 7,p. 7974 - 7983
[9]European Journal of Medicinal Chemistry,1993,vol. 28,p. 801 - 810
[10]Journal of Medicinal Chemistry,1986,vol. 29,p. 2174 - 2183
[11]Bollettino Scientifico della Facolta di Chimica Industriale di Bologna,1957,vol. 15,p. 51
Chem.Abstr.,1957
[12]Journal of Organic Chemistry,1957,vol. 22,p. 1263
[13]Bulletin de la Societe Chimique de France,1957,p. 714,716
[14]Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical and Analytical,1989,vol. 28,p. 74 - 76
[15]Molecular Crystals and Liquid Crystals Science and Technology, Section A: Molecular Crystals and Liquid Crystals,2001,vol. 364,p. 547 - 556
[16]Patent: EP641797,1995,A1
[17]Organic Process Research and Development,2012,vol. 16,p. 1717 - 1726
[18]Physical Chemistry Chemical Physics,2012,vol. 14,p. 14306 - 14314
[19]Polyhedron,2013,vol. 65,p. 252 - 261
[20]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 3234 - 3245
[21]Monatshefte fur Chemie,2016,vol. 147,p. 435 - 443
[22]European Journal of Medicinal Chemistry,2016,vol. 122,p. 429 - 435
[23]Organic and Biomolecular Chemistry,2016,vol. 14,p. 9814 - 9822
[24]ACS Combinatorial Science,2016,vol. 18,p. 616 - 624
[25]European Journal of Medicinal Chemistry,2018,vol. 160,p. 207 - 228
[26]Patent: WO2006/117657,2006,A1 .Location in patent: Page/Page column 19
[27]Patent: WO2019/67511,2019,A1 .Location in patent: Sheet 7
[28]Tetrahedron Letters,2013,vol. 54,p. 6959 - 6963

2
[ 698-17-9 ]
[ 1594-57-6 ]
[ 3035-88-9 ]

Reference： [1]Chemische Berichte,1965,vol. 98,p. 1293 - 1307

3
[ 698-17-9 ]
[ 1594-57-6 ]
[ 3035-87-8 ]

Reference： [1]Chemische Berichte,1965,vol. 98,p. 1293 - 1307

4
[ 5980-97-2 ]
[ 1594-57-6 ]
[ 32230-42-5 ]

Reference： [1]Journal of Heterocyclic Chemistry,1971,vol. 8,p. 205 - 208

5
[ 13922-41-3 ]
[ 1594-57-6 ]
[ 32212-18-3 ]

Reference： [1]Journal of Heterocyclic Chemistry,1971,vol. 8,p. 205 - 208

6
[ 1594-57-6 ]
[ 98-80-6 ]
[ 32212-19-4 ]

Reference： [1]Journal of Heterocyclic Chemistry,1971,vol. 8,p. 205 - 208
[2]Journal of Chemical and Engineering Data,2007,vol. 52,p. 718 - 720

7
[ 100-48-1 ]
[ 1594-57-6 ]

Yield	Reaction Conditions	Operation in experiment
93%	With sodium hydroxide; hydroxylamine hydrochloride In ethanol; water
87%	With hydroxylamine hydrochloride; sodium carbonate In water at 70℃; for 14h;
71%	With hydroxylamine hydrochloride; sodium hydrogencarbonate In ethanol; water for 6h; Reflux;	Procedure for the Preparation of (Z)-2-N'-hydroxyisonicotinamidine(2) Sodium bicarbonate (70 mmol, 5.88 g)was added in portions to a solution of hydroxylaminehydrochloride (70 mmol, 4.79 g) in 18mLofwater.Asolution of 4-cyanopyridine (35 mmol,3.64 g) in 34 mL of ethanol was then added, and the mixture stirred under reflux for 6 hr.The precipitate formed was filtered off and recrystallized from ethanol. Yield 71%; m.p.207-209° C.

48%	With hydroxylamine hydrochloride; triethylamine In ethanol for 24h; Heating;
39.5%	With hydroxylamine hydrochloride; potassium carbonate In ethanol for 12h; Reflux;	4.2.2.1 (Z)-N′-Hydroxy-pyridine-2-carboxamidine (45) General procedure: 2-cyanopyridine (2.5g, 24.01mmol) was dissolved in EtOH (60mL) treated with K2CO3 (5.97g; 43.22mmol; 1.8 equiv) and H2NOH·HCl (3.0g; 43.22mmol; 1.8 equiv) and heated to reflux for 12h. The mixture was diluted with diethyl ether when it was cooled to room temperature. The product was collected by filtration, washed with water, and dried under an infrared lamp. The compound was used without further purification. Yield: 1.5g (45.5%).
	With hydroxylamine hydrochloride; triethylamine In methanol at 20℃;

Reference： [1]Lessel [Archiv der Pharmazie, 1993, vol. 326, # 7, p. 383 - 389]
[2]Ozcan, Sevil; Kazi, Aslamuzzaman; Marsilio, Frank; Fang, Bin; Guida, Wayne C.; Koomen, John; Lawrence, Harshani R.; Sebti, Saïd M. [Journal of Medicinal Chemistry, 2013, vol. 56, # 10, p. 3783 - 3805]
[3]Prabhuswamy; Dinesha; Pampa; Kumar, S. Madan; Nagaraja; Lokanath [Molecular Crystals and Liquid Crystals, 2014, vol. 593, # 1, p. 243 - 252]
[4]Moloney, Gerard P.; Angus, James A.; Robertson, Alan D.; Stoermer, Martin J.; Robinson, Michael; Wright, Christine E.; McRae, Ken; Christopoulos, Arthur [European Journal of Medicinal Chemistry, 2008, vol. 43, # 3, p. 513 - 539]
[5]Xu, Li-Li; Wu, Yu-Feng; Wang, Lei; Li, Cui-Cui; Li, Li; Di, Bin; You, Qi-Dong; Jiang, Zheng-Yu [European Journal of Medicinal Chemistry, 2018, vol. 157, p. 1376 - 1394]
[6]Fish, Paul V.; Allan, Gillian A.; Bailey, Simon; Blagg, Julian; Butt, Richard; Collis, Michael G.; Greiling, Doris; James, Kim; Kendall, Jackie; McElroy, Andrew; McCleverty, Dawn; Reed, Charlotte; Webster, Robert; Whitlock, Gavin A. [Journal of Medicinal Chemistry, 2007, vol. 50, # 15, p. 3442 - 3456]

8
[ 102-52-3 ]
[ 1594-57-6 ]
[ 142114-64-5 ]

Reference： [1]Tetrahedron Letters,1992,vol. 33,p. 2195 - 2198
[2]Tetrahedron Letters,1992,vol. 33,p. 2195 - 2198

9
[ 5436-21-5 ]
[ 1594-57-6 ]
[ 142114-66-7 ]

Reference： [1]Tetrahedron Letters,1992,vol. 33,p. 2195 - 2198

10
[ 51987-73-6 ]
[ 1594-57-6 ]
[ 154345-83-2 ]

Reference： [1]European Journal of Medicinal Chemistry,1993,vol. 28,p. 801 - 810

11
[ 1594-57-6 ]
[ 102-92-1 ]
[ 103499-23-6 ]

Reference： [1]Journal of Medicinal Chemistry,1986,vol. 29,p. 2174 - 2183

12
[ 1594-57-6 ]
[ 123-54-6 ]
[ 142114-73-6 ]

Reference： [1]Tetrahedron Letters,1992,vol. 33,p. 2195 - 2198

13
[ 1594-57-6 ]
[ 42588-57-8 ]
[ 142114-69-0 ]

Reference： [1]Heterocycles,1998,vol. 48,p. 961 - 973
[2]Tetrahedron Letters,1992,vol. 33,p. 2195 - 2198

14
[ 1594-57-6 ]
[ 4185-99-3 ]

Reference： [1]Synthetic Communications,1988,vol. 18,p. 1427 - 1432
[2]Phosphorus, Sulfur and Silicon and the Related Elements,2005,vol. 180,p. 2653 - 2666
[3]Journal of Heterocyclic Chemistry,2009,vol. 46,p. 1271 - 1279

15
[ 1594-57-6 ]
[ 119868-06-3 ]

Reference： [1]Synthetic Communications,1988,vol. 18,p. 1427 - 1432

16
[ 51731-17-0 ]
[ 1594-57-6 ]
[ 142114-66-7 ]

Reference： [1]Heterocycles,1998,vol. 48,p. 961 - 973

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 1 3.4 g (0.024 mol) of pydridine-4-amidoxime in 100 ml of dimethyl formamide are introduced into the reactor, and 7.2 g (0.02 mol) of 4'-benzoxazolyl-2-stilbene-4-carboxylic acid chloride are added. Subsequently, the mixture is stirred for 1 hour at room temperature, and then refluxed for 2 hours. Suction-filtration is carried out at room temperature, and the filter residue is washed with dimethyl formamide and methanol. After drying, 7.8 g (87.6% of the theory) of the compound having the formula STR10 are obtained in the form of a light yellow powder, which, after recrystallization from N-methylpyrrolidone and clarification with animal charcoal has a liquid/crystalline transition temperature of 274-275 C. and a melting point of 281 C. Analysis: Calc.: C, 76.0%, H, 4.1%, N, 12.7%; Found: C, 75.8%, H, 4.2%, N, 12.8%. Absorption (in DMF): max=367 nm=74500. Fluorescence (in DMF): max=432 nm. The pyridine-4-amidoxime used is obtained in the following manner:

19
[ 1594-57-6 ]
[ 108-24-7 ]
[ 123865-77-0 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1560 - 1563

20
[ 1594-57-6 ]
[ 79-22-1 ]
C₈H₉N₃O₃ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1560 - 1563

21
[ 1594-57-6 ]
[ 6160-65-2 ]
[ 345631-77-8 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1560 - 1563

22
[ 335-64-8 ]
[ 1594-57-6 ]
[ 894796-31-7 ]

Reference： [1]Heterocycles,2006,vol. 68,p. 307 - 321
[2]Physical Chemistry Chemical Physics,2012,vol. 14,p. 14306 - 14314

23
[ 59748-37-7 ]
[ 1594-57-6 ]
4-[5-(4'-pentyl-biphenyl-4-yl)-[1,2,4]oxadiazol-3-yl]-pyridine [ No CAS ]

Reference： [1]Molecular Crystals and Liquid Crystals Science and Technology, Section A: Molecular Crystals and Liquid Crystals,2001,vol. 364,p. 547 - 556

24
[ 1594-57-6 ]
[ 66227-34-7 ]
4-{5-[4-(4-pentyl-cyclohexyl)-phenyl]-[1,2,4]oxadiazol-3-yl}-pyridine [ No CAS ]

Reference： [1]Molecular Crystals and Liquid Crystals Science and Technology, Section A: Molecular Crystals and Liquid Crystals,2001,vol. 364,p. 547 - 556

25
[ 1594-57-6 ]
[ 82492-58-8 ]
4-{5-[4-(4-propyl-cyclohexyl)-phenyl]-[1,2,4]oxadiazol-3-yl}-pyridine [ No CAS ]

Reference： [1]Molecular Crystals and Liquid Crystals Science and Technology, Section A: Molecular Crystals and Liquid Crystals,2001,vol. 364,p. 547 - 556

26
[ 39520-24-6 ]
[ 1594-57-6 ]
4-methyl-2-(3-pyridin-4-yl-[1,2,4]oxadiazol-5-yl)-pentanoic acid methyl ester [ No CAS ]

Reference： [1]Tetrahedron Letters,2006,vol. 47,p. 4271 - 4274

27
[ 500-76-5 ]
[ 1594-57-6 ]
4-[4-(3-pyridin-4-yl-[1,2,4]oxadiazol-5-yl)-phenoxy]-phenol [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5822 - 5826

28
[ 1594-57-6 ]
N-methyl-4-(5-pentadecafluoroheptyl-1,2,4-oxadiazol-3-yl)pyridinium iodide [ No CAS ]

Reference： [1]Heterocycles,2006,vol. 68,p. 307 - 321

29
[ 1594-57-6 ]
N-methyl-4-(5-pentadecafluoroheptyl-1,2,4-oxadiazol-3-yl)pyridinium trifluoromethanesulfonate [ No CAS ]

Reference： [1]Heterocycles,2006,vol. 68,p. 307 - 321

30
[ 1594-57-6 ]
[ 102227-52-1 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1560 - 1563

31
[ 1594-57-6 ]
[ 345631-77-8 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1560 - 1563

32
[ 1594-57-6 ]
2,2-dimethyl-propionic acid 3-pyridin-4-yl-[1,2,4]oxadiazol-5-ylsulfanylmethyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1560 - 1563
[2]Journal of Medicinal Chemistry,2001,vol. 44,p. 1560 - 1563

33
[ 1594-57-6 ]
2,2-dimethyl-propionic acid 5-oxo-3-pyridin-4-yl-[1,2,4]oxadiazol-4-ylmethyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 1560 - 1563

34
[ 1594-57-6 ]
[ 103499-31-6 ]

Reference： [1]Journal of Medicinal Chemistry,1986,vol. 29,p. 2174 - 2183

35
[ 1594-57-6 ]
[ 103499-22-5 ]

Reference： [1]Journal of Medicinal Chemistry,1986,vol. 29,p. 2174 - 2183

36
[ 1594-57-6 ]
(D,L)-5-(1-amino-2-phenylethyl)-3-(4-pyridyl)-1,2,4-oxadiazole [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,1993,vol. 28,p. 801 - 810

37
[ 55-22-1 ]
[ 1594-57-6 ]

Reference： [1]Doklady Bolgarskoi Akademii Nauk,1958,vol. 11,p. 287

38
[ 1594-57-6 ]
[ 543-27-1 ]
[ 857653-93-1 ]

Yield	Reaction Conditions	Operation in experiment
		Preparation 10: 3-Pyridin-4-yl- [1, 2,4] oxadiazol-5-ylmethylcarbonic acid isobutyl ester Isobutylchloroformate (11.67ml, 90mmol) was added to a solution of hydroxyacetic acid (3.42g, 45mmol) and triethylamine (12. 65ml, 90mmol) in toluene (220ml) at 0C. After stirring at rt for lh, N-hydroxyisonicotinamidine (6.17g, 45mmol) and powdered 3A molecular sieves (20g) were added. After heating under reflux for 18h, the cooled mixture was filtered through celite, the solvent evaporated and the residue purified by flash chromatography aH- EtOAc, 1: 1) to afford the title compound: RT = 3. 51min; m/z (ES+) = 278. 0 [M+Eq+.

Reference： [1]Patent: WO2005/61489,2005,A1 .Location in patent: Page/Page column 26

39
[ 1594-57-6 ]
[ 857653-91-9 ]

Yield	Reaction Conditions	Operation in experiment
		Preparation 8: (3-Pyridin4-yl- [1, 2,4] oxadiazol-5-ylmethyl) carbamic acid tert-butyl ester A solution of tert-butoxycarbonylaminoacetic acid (l. Og, 5. 71mmol) and triethylamine (802gel, 5. 71mmol) in toluene (30ml) was cooled to 0C and isobutylchloroformate (740gel, 5. 71mmol) introduced dropwise. The reaction mixture was stirred at 0C for lOmin and at rt for 30min, whereupon N-hydroxyisonicotinamidine (652mg, 4.76mmol) and powdered 3A molecular sieves (4g) were added. After heating under reflux for 12h the reaction was cooled, filtered through celite and the solvent removed in vacuo. The residue was dissolved in EtOAc (200ml) and washed with water (30ml) and saturated aqueous NaHCO3 (30ml), then dried (MgS04). The solvent was removed and the residue purified by flash chromatography (IH- EtOAc, 2 : 3) to afford the title compound: RT = 2.97 min; m/z (ES+) = 277.1 [M+H]+.

Reference： [1]Patent: WO2005/61489,2005,A1 .Location in patent: Page/Page column 25-26

40
[ 1594-57-6 ]
PSN₆₃₂₄₀₈ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 1: 4- (3-Pyridin-4-yl- [1, 2,4] oxadiazol-5-ylmethoxy) piperidine-1-carboxylic acid tert- butyl ester A stirred solution of triethylamine (123mul, 0. 87mmol) and 4-carboxymethoxypiperidine- 1-carboxylic acid tert-butyl ester (Preparation 1,227mg, 0. 87mmo1) in toluene (10ml) was treated with isobutylchloroformate (113mul, 0. 87mmol). After 20min, activated powdered 3A molecular sieves (0.7g) andN-hydroxyisonicotinamidine (lOOmg, 0. 73mmol) were added and the mixture heated under reflux for 18h. On cooling, the mixture was filtered through celite, the solvent removed in vacuo and the residue purified by flash chromatography (IH-EtOAc, 7: 13) to afford the title compound: RT = 3. 29min ; m/z (ES+) 361.3 [M+H] + ; OH (CDC13) 1.40 (9H, s), 1.55-1. 63 (2H, m), 1.80-1. 92 (2H, m), 3.05-3. 15 (2H, m), 3.64-3. 79 (3H, m), 4.80 (2H, s), 7.90 (2H, d), 8.75 (2H, d).

Reference： [1]Patent: WO2005/61489,2005,A1 .Location in patent: Page/Page column 31-32

41
[ 1594-57-6 ]
trans-4-(3-pyridin-4-yl-[1,2,4]oxadiazol-5-yl)cyclohexanecarboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Preparation 3: trans-4- (3-Pyridin-4-yl- [1, 2,4] oxadiazol-5-yl) cyclohexanecarboxylic acid methyl ester A solution of cyclohexane-1, 4-dicarboxylic acid monomethyl ester (1.053g, 5.66mmol) and triethylamine (800gel, 5. 66mmol) in toluene (30ml) was cooled to 0C and isobutylchloroformate (735} il, 5. 66mmol) introduced dropwise. The mixture was stirred at rt for 30min whereupon activated, powdered 3A molecular sieves (5g) and N- hydroxyisonicotinamidine (705mg, 5.14mmol) were added. The mixture was heated under reflux for 18h, cooled and filtered through celite. The solvent was removed in vacuo and the residue purified by flash chromatography (IH-EtOAc, 1: 1) to afford the title compound: RT = 3. 20min ; m/z (ES) = 288. 2 [M+H] +.

Reference： [1]Patent: WO2005/61489,2005,A1 .Location in patent: Page/Page column 24

42
[ 33233-67-9 ]
[ 1594-57-6 ]
4-(3-pyridin-4-yl-[1,2,4]oxadiazol-5-yl)-benzylamine dihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%		To a solution of 4- (Boc-aminomethyl)-benzoic acid (187 mg) in DMF (0.25 M) were added DIEA (5 eq), TBTU (1 eq) and HOBt (0.2 eq). The solution was stirred at RT for 3 minutes, and then isonicotinamide oxime (102mg, 1 eq) was added. After 1 hour, the solvent was evaporated. The residue was triturated with 0.05 M NaOH (5 ml). The solid was filtered off, washed with water and dried under vacuum. The solid was dissolved in DMF (0.25 M). The reaction mixture was heated at 110C for 2 hours. The reaction mixture was cooled down at RT. The precipitate was filtered off, washed with water, and then dried under vacuum. The solid was dissolved in 3N HCI. The solution was heated at 50C for 2 hours. The solvent was evaporated and the residue was dried under vacuum. The title product was obtained as a white powder (74% yield).'H NMR (300 MHz, DMSO-d6): 4.15 ppm (q, 2H, J=5.7 Hz); 5.00 ppm (bs, 2H); 7.80 ppm (d, 2H, J=8.4 Hz); 8.24 ppm (m, 4H); 8.95 ppm (d, 2H, J=6.0 Hz).

Reference： [1]Patent: WO2005/82367,2005,A1 .Location in patent: Page/Page column 50

43
[ 1594-57-6 ]
[ 86427-02-3 ]
[ 478488-61-8 ]

Yield	Reaction Conditions	Operation in experiment
31 mg (29%)	With pyridine; In 1,4-dioxane; water;	EXAMPLE 14 5-(3-Chloro-thiophen-2-yl)-3-(pyridin-4-yl)-[1,2,4]-oxadiazole A solution of 3-chloro-thiophene-2-carbonyl chloride (72 mg, 0.40 mmol) and 4-pyridinylamidoxime (55 mg, 0.40 mmol) in 1,4-dioxane (9 mL) and pyridine (1 mL) was refluxed for 3.5 h, heated at 55 C. for 15 h, then refluxed for 5 h. The solution was cooled to room temperature and the product was precipitated by addition of 20 mL of water. The precipitate was filtered and washed with cold water, then dried to yield 31 mg (29%) of the title compound. 1H NMR (CDCl3): 8.81 (d, J=6.05 Hz, 2H), 8.03 (dd, J=4.40, 1.65 Hz, 2H), 7.64 (d, J=5.22 Hz, 1H), 7.15 (d, J=5.22 Hz, 1H).

Reference： [1]Patent: US2003/45546,2003,A1

44
3,4-Dimethylpyrrolo[3,2-b]carbazole-2-carboxylic acid [ No CAS ]
[ 1594-57-6 ]
3,4-Dimethyl-2-[3-(pyridin-4-yl)-1,2,4-oxadiazol-5-yl]pyrrolo[3,2-b]carbazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; water; 1,1'-carbonyldiimidazole; mineral oil;	EXAMPLE 17 3,4-Dimethyl-2-[3-(4-pyridyl)-1,2,4-oxadiazol-5-yl]pyrrolo[3,2-b]carbazole 3,4-Dimethylpyrrolo[3,2-b]carbazole-2-carboxylic acid (0.556 g, 2 mmol), (prepared as described in WO93/01512) and carbonyl diimidazole (0.37 g, 2.2 mmol) were dissolved in freshly distilled tetrahydrofuran (10 ml) in an oven-dried flask under a nitrogen atmosphere. The resulting orange solution was stirred at room temperature for 2 hours, by which time it was an orange suspension, and complete conversion of the acid to the imidazolide intermediate was verified by TLC. Meanwhile, in a second oven-dried flask, 4-pyridylamidoxime (0.557 g, 4.1 mmol) was dissolved in THF (20 ml). To this was added crushed 3 A sieves (0.66 g) and the mixture was stirred at room temp for 1 hour. Sodium hydride (60% dispersion in mineral oil, 0.161 g, 4 mmol) was added and the mixture stirred for a further 1 hour. The contents of the two flasks were combined and stirred at room temp for 18 hours, by which time TLC showed complete consumption of the imidazolide intermediate. The yellow precipitate which had formed was filtered off and taken up into hot DMSO. This was filtered and water was added. On cooling, yellow crystals of the title compound formed, were filtered off and dried (vacuum oven/85 C.) (0.265 g, 35%) m.p. >300 C. (decomp.) (Found: C, 71.37; H, 4.49; N, 17.94. C23 H17 N5 O.0.4H2 O requires: C, 71.45; H, 4.64; N, 18.11%); deltaH ?2 H6!-DMSO 11.85 (1H, s, 1-NH), 10.70 (1H, s, 5-NH), 8.17 and 8.05 (4H, AB quart, J 5.5, pyridine), 8.13 (1H, d, J 7.5, 9-H), 7.95 (1H, s, 10-H), 7.48-7.32 (2H, m, 6-H, 7-H), 7.10 (1H, ddd, J 7.5, 5.5, 2, 8-H), 3.08 and 2.95 (23H, 2s, 3-CH3 and 4-CH3); m/z (%) 379 (5, M+), 259 (42), 224 (61), 193 (100); numax (KBr disc)/cm-1 3439, 3244, 1610, 1500, 1414, 1371, 1311, 1242.

Reference： [1]Patent: US5770598,1998,A

45
[ 1594-57-6 ]
[ 108-24-7 ]
[ 64-19-7 ]
pyridine-4-carboximidamide acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		The compound obtained from step a above (145.98mmoles, 2Og) was dissolved in glacial acetic acid (100ml) and acetic anhydride (218.98mmoles, 20.64ml) and stirred for 5 minutes. To the resulting reaction mixture was added palladium on carbon (1Og, 10%) and hydrogenated at 45-50 psi for 2hrs. The mixture was filtered through celite pad and washed with glacial acetic acid. The filtrate was concentrated under reduced pressure and excess glacial acetic acid was removed by co-evaporating the residue with n-heptane for approximately four times to furnish the title compound. Yield: 18g.

Reference： [1]Patent: WO2006/117657,2006,A1 .Location in patent: Page/Page column 20

46
[ 100-48-1 ]
[ 5470-11-1 ]
[ 1594-57-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium methylate; In methanol; isopropyl alcohol;	70 g (1 mol) of hydroxyammonium chloride in 500 ml of methanol are introduced into the vessel, and a solution of 54 g (1 mol) of sodium methylate in 500 ml of methanol is added. After about 30 minutes, the sodium chloride is filtered off, 41.6 g (0.4 mol) of pyridine-4-carboxylic acid nitrile are added to the filtrate, and the batch is refluxed for 24 hours. Subsequently, the methanol is distilled off, and the residue is recrystallized from 2000 ml of isopropanol with simultaneously clarification with bleaching earth. 49.1 g (89.5% of th., relative to the nitrile used) of pyridine-4-amidoxime having a melting point of 207-208 C. are obtained which are reacted without further purification.

Reference： [1]Patent: US4310665,1982,A

47
ammonium thiocyanate [ No CAS ]
[ 1594-57-6 ]
nickel(II) perchlorate [ No CAS ]
Ni(C₅H₄NCHNONH₂)4⁽²⁺⁾*2NCS^(1-)=Ni(C₅H₄NCHNONH₂)4(NCS)2 [ No CAS ]

Reference： [1]Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical and Analytical,1989,vol. 28,p. 74 - 76

48
ammonium thiocyanate [ No CAS ]
cobalt(II) perchlorate [ No CAS ]
[ 1594-57-6 ]
Co(C₅H₄NCHNONH₂)4⁽²⁺⁾*2NCS^(1-)=Co(C₅H₄NCHONNH₂)4(NCS)2 [ No CAS ]

Reference： [1]Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical and Analytical,1989,vol. 28,p. 74 - 76

49
[ 1594-57-6 ]
cobalt(II) bromide [ No CAS ]
[ 121380-68-5 ]

Reference： [1]Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical and Analytical,1989,vol. 28,p. 74 - 76

50
[ 1594-57-6 ]
nickel dibromide [ No CAS ]
[ 121380-65-2 ]

Reference： [1]Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical and Analytical,1989,vol. 28,p. 74 - 76

51
[ 1594-57-6 ]
[ 7646-79-9 ]
[ 121380-67-4 ]

Reference： [1]Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical and Analytical,1989,vol. 28,p. 74 - 76

52
[ 1594-57-6 ]
nickel dichloride [ No CAS ]
[ 121380-64-1 ]

Reference： [1]Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical and Analytical,1989,vol. 28,p. 74 - 76

53
[ 923288-55-5 ]
[ 1594-57-6 ]
[ 923287-53-0 ]

Yield	Reaction Conditions	Operation in experiment
62%		Example 1a; 3-Nitro-5-[3-(1-oxy-pyridin-4-yl)-[1,2,4]oxadiazol-5-yl]-benzene-1,2-diol (compound 4, Table 1). a) To a stirred solution of 3,4-dibenzyloxy-5-nitrobenzoic acid (0.5 g, 1.32 mmol) in dimethylformamide (5 mL) at room temperature was added 1,1-carbonyldiimidazole (0.246 g, 1.52 mmol) in one portion. After stirring for one hour, N'-hydroxypyridine-4- carboximidamide (0.208 g, 1.52 mmol) was added in one portion and the resulting mixture was stirrred at room temperature overnight. The mixture was then stirred at 110 C for three hours and then allowed to cool to room temperature. The mixture was poured onto ice-water (100 mL) and extracted with 20% isopropanol/dichloromethane. The organic extracts were washed with water and brine, then dried (Na2SO4), filtered and evaporated to leave a solid residue that was recrystallised from ethanol. 4-[5-(3,4-Bis-benzyloxy-5-nitro- phenyl)-[l,2,4]oxadiazol-3-yl]-pyridine was obtained as a beige solid (0.395 g, 62%).

Reference： [1]Patent: WO2007/13830,2007,A1 .Location in patent: Page/Page column 37

54
[ 847408-56-4 ]
[ 1594-57-6 ]
[ 1059063-71-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4267 - 4274

55
[ 1594-57-6 ]
[ 4755-77-5 ]
[ 163719-80-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 3661 - 3666
[2]Russian Journal of Organic Chemistry,2014,vol. 50,p. 1683 - 1686
Zh. Org. Khim.,2014,vol. 50,p. 1694 - 1697,4

56
[ 929028-43-3 ]
[ 1594-57-6 ]
C₁₃H₈F₃N₃O₃S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 6083 - 6087

57
[ 1594-57-6 ]
[ 103-85-5 ]
[ 123865-80-5 ]

Reference： [1]Journal of Chemical Research,2008,p. 235 - 239

58
[ 1594-57-6 ]
[ 538-75-0 ]
[ 903164-68-1 ]

Reference： [1]Journal of Chemical Research,2008,p. 235 - 239

59
[ 1594-57-6 ]
[ 74-88-4 ]
N-hydroxycarbamimidoyl-1-methyl-4-pyridynium iodide [ No CAS ]

Reference： [1]Letters in Organic Chemistry,2009,vol. 6,p. 500 - 503
[2]Journal of Heterocyclic Chemistry,2009,vol. 46,p. 1271 - 1279

60
[ 463-72-9 ]
[ 1594-57-6 ]
[ 102227-52-1 ]

Reference： [1]Journal of Heterocyclic Chemistry,2009,vol. 46,p. 1271 - 1279

61
[ 19009-39-3 ]
[ 1594-57-6 ]
[ 1206768-72-0 ]

Reference： [1]Journal of Heterocyclic Chemistry,2009,vol. 46,p. 1271 - 1279

62
[ 1594-57-6 ]
[ 541-41-3 ]
[ 102227-52-1 ]

Reference： [1]Journal of Heterocyclic Chemistry,2009,vol. 46,p. 1271 - 1279

63
[ 1594-57-6 ]
[ 88-10-8 ]
[ 1206768-68-4 ]

Reference： [1]Journal of Heterocyclic Chemistry,2009,vol. 46,p. 1271 - 1279

64
[ 91004-48-7 ]
[ 1594-57-6 ]
C₁₅H₁₄N₄O₆ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 3396 - 3411

65
[ 1594-57-6 ]
[ 208108-76-3 ]
[ 1201444-43-0 ]

Yield	Reaction Conditions	Operation in experiment
56%		4- [5-(4-Phenyl-5-trifluoromethyl-thiophen-2-yl)- [ 1 ,2,4] oxadiazol-3-yI] - pyridine <n="155"/>In a round bottom flask, a stirring solution of 3,4-diethoxybenzoic acid (lOOmg, 0.3673mmol) in DMF (1.8 mL) was treated sequentially with HOBt (64mg, 0.48 mmol)) and EDCI (91mg, 0.48mmol) at room temperature. The reaction was stirred for 20 min followed by addition, in a single portion of JV- hydroxyisonicotinimidamide (66mg, 0.48mmol). The reaction was stirred for additional 30 min at room temperature and then heated to 90-95 C for 1Oh. The reaction was cooled to room temperature, diluted with a saturated solution of NaCl and extracted with EtOAc (3X50mL). The organic phase was dried over Na2SO4 anhydrous and concentrated under reduced pressure. The product was purified by column chromatography using CH2Cl2:Me0H (9: 1 ) to offer the product as a pale yellow solid in 56% yield (78mg). 1H NMR (300 MHz, CDCl3): delta 8.82 (bs, 2H), 8.02 (d, J= 2.7, 2H), 7.93 (q, J= 1.5 Hz, IH), 7.47 (s, 5H); 13C NMR (75 MHz, CDCl3): delta 171.12, 167.81, 150.86, 145.70, 135.09, 134.12, 133.14, 123.32, 129.04, 126.35, 126.33, 121.67, 120.21, 105.04. MS (EI) m/z: 374 (M+), HRMS (EI) for C18Hi0F3N3SO (M+): calcd 374.0569, found 374.0579.

Reference： [1]Patent: WO2009/151529,2009,A1 .Location in patent: Page/Page column 152-153

66
[ 1594-57-6 ]
[ 6602-22-8 ]
4-(1-amino-1-hydroxyiminomethyl)-4'-hydroxyiminomethyl-1,1'-(prop-1,3-diyl)-bispyridinium dibromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	In N,N-dimethyl-formamide; at 70 - 80℃; for 8h;	General procedure: Initially the monoquaternary semi-product was prepared: a solution of the 4-hydroxyiminomethylpyridine (4.0 g, 32.8 mmol) and 1,3-dibromopropane (16.7 ml, 163.8 mmol) in acetone (30 ml) was stirred at reflux for 8 h. The reaction mixture was cooled to room temperature and the crystalline crude product collected by filtration and washed with acetone (3 × 20 ml). The solid crude product was recrystalized from MeCN (1 g of crude product per 100 ml of MeCN), where the boiling mixture was filtered under a reduced pressure. The filtrate was evaporated under a reduced pressure to produce the pure monoquaternary salt of 1-(3-bromopropyl)-4-hydroxyiminomethylpyridinium bromide (72%).48Secondly, the synthesis of the bisquaternary salt was completed. A solution of the monoquaternary salt (0.50 g, 1.5 mmol) and selected heteroaromatic compound (0.38 g, 3.0 mmol) in DMF (10 ml) was stirred at 70-80 C for 8 h. The reaction mixture was cooled to room temperature and portioned with acetone (80 ml); the crystalline crude product was collected by filtration, washed with acetone (3 × 20 ml) and recrystallized from boiling MeCN. The pure bisquaternary salt was obtained as the solid compound insoluble in boiling MeCN.48

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 754 - 762

67
[ 1594-57-6 ]
[ 6345-27-3 ]

Reference： [1]Synthetic Communications,2011,vol. 41,p. 2195 - 2199

68
[ 1594-57-6 ]
[ 118-41-2 ]
[ 446057-87-0 ]

Reference： [1]Russian Chemical Bulletin,2010,vol. 59,p. 2268 - 2275

69
[ 1594-57-6 ]
[ 143-15-7 ]
4-(-1-aminohydroxyimino-methyl)-1-dodecylpyridinium bromide [ No CAS ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2012,vol. 51,p. 611 - 616

70
[ 1594-57-6 ]
[ 93-02-7 ]
[ 1347755-37-6 ]

Reference： [1]Medicinal Chemistry Research,2012,vol. 21,p. 3043 - 3052

71
[ 1594-57-6 ]
[ 121-33-5 ]
[ 1347755-40-1 ]