[ CAS No. 2863-98-1 ] {[proInfo.proName]}

Name: 2863-98-1|4-Hydrazinylbenzonitrile hydrochloride|98%
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Quality Control of [ 2863-98-1 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 2863-98-1 ]

Product Details of [ 2863-98-1 ]

CAS No. :	2863-98-1	MDL No. :	MFCD00673994
Formula :	C₇H₈ClN₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	UXDLLFIRCVPPQP-UHFFFAOYSA-N
M.W :	169.61	Pubchem ID :	16212962
Synonyms :	4-Cyanophenylhydrazine hydrochloride	Chemical Name :	4-Hydrazinylbenzonitrile hydrochloride

Calculated chemistry of [ 2863-98-1 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	2.0
Molar Refractivity :	45.33
TPSA :	61.84 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-6.47 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	1.22
Log Po/w (WLOGP) :	1.46
Log Po/w (MLOGP) :	1.05
Log Po/w (SILICOS-IT) :	0.3
Consensus Log Po/w :	0.81

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.0
Solubility :	1.7 mg/ml ; 0.0101 mol/l
Class :	Very soluble
Log S (Ali) :	-2.12
Solubility :	1.3 mg/ml ; 0.00766 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.14
Solubility :	1.22 mg/ml ; 0.00721 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.63

Safety of [ 2863-98-1 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H312-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 2863-98-1 ]

* 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 [ 2863-98-1 ]
Downstream synthetic route of [ 2863-98-1 ]

[ 2863-98-1 ] Synthesis Path-Upstream 1~4

1
[ 2863-98-1 ]
[ 17672-27-4 ]

Reference： [1] Journal of Organic Chemistry, 2018, vol. 83, # 10, p. 5438 - 5449

2
[ 873-74-5 ]
[ 2863-98-1 ]

Yield	Reaction Conditions	Operation in experiment
84%	With hydrogenchloride; tin(II) chloride dihdyrate; sodium nitrite In water at -5 - 0℃; for 0.25 h;	To a cooled (−5 to 0°C) stirred suspension of 4-aminobenzonitrile (50g, 423mmol) in concentrated hydrochloric acid (550mL) was added dropwise aqueous sodium nitrite solution (31.5g, 457mmol in 200mL water). To this diazotised solution cooled (0°C) solution of tin (II) chloride dihydrate (477g, 2.1mol) in concentrated hydrochloric acid (370mL) was added while stirring and maintaining the temperature below 0°C. The resulting solution was further stirred for 15min. White precipitates so formed were collected by filtration, washed with diethylether and crystallized from aqueous ethanol. Mp 234–236°C (Lit. mp 235–237°C), yield 60g (84percent).

Reference： [1] Journal of the American Chemical Society, 2016, vol. 138, # 30, p. 9377 - 9380
[2] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 15, p. 4581 - 4590
[3] Synthetic Communications, 2014, vol. 44, # 24, p. 3563 - 3571
[4] Journal of Medicinal Chemistry, 1994, vol. 37, # 19, p. 3023 - 3032
[5] Angewandte Chemie - International Edition, 2013, vol. 52, # 47, p. 12426 - 12429[6] Angew. Chem., 2013, vol. 125, # 47, p. 12652 - 12656,4
[7] Journal of Agricultural and Food Chemistry, 2014, vol. 62, # 2, p. 381 - 390
[8] Journal of the Chinese Chemical Society, 2018, vol. 65, # 5, p. 538 - 547

3
[ 3058-39-7 ]
[ 2863-98-1 ]

Reference： [1] Chinese Journal of Chemistry, 2018, vol. 36, # 11, p. 1003 - 1006

4
[ 33348-34-4 ]
[ 1019995-59-5 ]
[ 2863-98-1 ]

Reference： [1] Journal of Medicinal Chemistry, 2008, vol. 51, # 7, p. 2196 - 2207

[ 2863-98-1 ] Synthesis Path-Downstream 1~37

1
[ 29882-07-3 ]
[ 2863-98-1 ]
[ 46276-24-8 ]

Reference： [1]Tetrahedron Letters,1993,vol. 34,p. 4705 - 4708

2
[ 2863-98-1 ]
[ 104618-32-8 ]
[ 147009-18-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium acetate; In acetic acid;	4-Cyanophenyl hydrazine hydrochloride (4.41 g, 0.026 mole) was dissolved in acetic acid (100 ml) and sodium acetate (2 g) was added. 4-Phthalimido cyclohexanone (6.4 g, 0.026 mole) was added and the mixture heated under reflux overnight. The solvent was removed in vacuo and the residue triturated with methanol to give 3-phthalimido-6-cyano-1,2,3,4-tetrahydrocarbazole as a beige solid, (5.3 g).

Reference： [1]Journal of medicinal chemistry,1993,vol. 36,p. 1918 - 1919
[2]Patent: EP603432,1994,A1

3
[ 29882-07-3 ]
[ 2863-98-1 ]
3-(2-aminoethyl)-5-cyano-1H-indole hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 3023 - 3032

4
[ 873-74-5 ]
[ 2863-98-1 ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: 4-Aminobenzonitrile With hydrogenchloride; sodium nitrite In water; acetic acid at 0℃; for 0.833333h; Stage #2: With hydrogenchloride; tin(II) chloride dihdyrate In water; acetic acid at 0 - 20℃; for 1.33333h;
84%	With hydrogenchloride; tin(II) chloride dihdyrate; sodium nitrite In water at -5 - 0℃; for 0.25h;	1 4.1 Synthesis of 4-hydrazinylbenzonitrile hydrochloride (4) To a cooled (-5 to 0°C) stirred suspension of 4-aminobenzonitrile (50g, 423mmol) in concentrated hydrochloric acid (550mL) was added dropwise aqueous sodium nitrite solution (31.5g, 457mmol in 200mL water). To this diazotised solution cooled (0°C) solution of tin (II) chloride dihydrate (477g, 2.1mol) in concentrated hydrochloric acid (370mL) was added while stirring and maintaining the temperature below 0°C. The resulting solution was further stirred for 15min. White precipitates so formed were collected by filtration, washed with diethylether and crystallized from aqueous ethanol. Mp 234-236°C (Lit. mp 235-237°C), yield 60g (84%).
82%	Stage #1: 4-Aminobenzonitrile With hydrogenchloride; sodium nitrite In water at -10℃; Stage #2: With hydrogenchloride; tin(II) chloride dihdyrate In water at -10℃;

	With hydrogenchloride; tin(ll) chloride; sodium nitrite 2.) 15 min; Yield given. Multistep reaction;
	With hydrogenchloride; tin(ll) chloride; sodium nitrite In water at 0 - 5℃; for 0.75h; Inert atmosphere;
	Stage #1: 4-Aminobenzonitrile With hydrogenchloride; sodium nitrite In water at -10 - 0℃; for 0.5h; Stage #2: With hydrogenchloride; tin(II) chloride dihdyrate In water
	Stage #1: 4-Aminobenzonitrile With hydrogenchloride; sodium nitrite In water at 0 - 5℃; for 1h; Stage #2: With thionyl chloride In water at 0 - 20℃;
	Stage #1: 4-Aminobenzonitrile With hydrogenchloride; sodium nitrite In water at -5℃; for 0.5h; Stage #2: With tin(ll) chloride In water at 20℃; for 1h;	5.2.5. typical procedure for the synthesis of hydrazine hydrochlorideintermediates (10) General procedure: dissolve the substituted anline (3 mmol) in HCl aq (6 M) at -5 °C,and slowly added an aqueous solution of NaNO2 (0.23 g, 3.3 mmol).The mixture was stirred for further 0.5 h, a solution of SnCl2 (1.7 g,7.5 mmol) dissolved in concentrated HCl was added dropwise, then the resulting mixture was moved to room temperature and stirred for further1 h. The muddy mixture was filtered out, washed with a small amount of HCl solution and dried in vacuum. This desired phenylhydrazine hydrochloride intermediate was used directly without additional purification.To a solution of substituted benzyl halide 3 mmol in EtOH was added the hydrazine hydrate 30 mmol, and the mixture was stirred atroom temperature overnight till the reaction was completed monitored by TLC. The reaction mixture was concentrated to dryness, and redissolvedin a little EtOH, then added an aqueous HCl (12 M) andstirred for a while at 0 °C. The resulting precipitate was collected byfiltration and dried. This desired benzylhydrazine hydrochloride intermediatewas used directly without additional purification.
	Multi-step reaction with 2 steps 1.1: hydrogenchloride / water 1.2: 1 h / 2 °C 2.1: sodium hydrogensulfite / water / 2 h / 85 °C 2.2: 0.5 h / 50 °C

Reference： [1]Gallagher, Nolan M.; Bauer, Jackson J.; Pink, Maren; Rajca, Suchada; Rajca, Andrzej [Journal of the American Chemical Society, 2016, vol. 138, # 30, p. 9377 - 9380]
[2]Chandna, Nisha; Kumar, Satish; Kaushik, Pawan; Kaushik, Dhirender; Roy, Somendu K.; Gupta, Girish K.; Jachak, Sanjay M.; Kapoor, Jitander K.; Sharma, Pawan K. [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 15, p. 4581 - 4590]
[3]Anitha; Reddy, B. Sudhakar; Sekhar; Reddy, K. Venugopal; Chandrasekhar [Synthetic Communications, 2014, vol. 44, # 24, p. 3563 - 3571]
[4]Castro, Jose L.; Baker, Raymond; Guiblin, Alexander R.; Hobbs, Sarah C.; Jenkins, Matthew; et al. [Journal of Medicinal Chemistry, 1994, vol. 37, # 19, p. 3023 - 3032]
[5]Zhao, Dongbing; Shi, Zhuangzhi; Glorius, Frank [Angewandte Chemie - International Edition, 2013, vol. 52, # 47, p. 12426 - 12429][Angew. Chem., 2013, vol. 125, # 47, p. 12652 - 12656,4]
[6]Xu, Renbo; Xia, Rui; Luo, Ming; Xu, Xiaoyong; Cheng, Jiagao; Shao, Xusheng; Li, Zhong [Journal of Agricultural and Food Chemistry, 2014, vol. 62, # 2, p. 381 - 390]
[7]Jin, Xiao-Yan; Zhang, Kang-Ping; Chen, Hao; Miao, Ting-Ting; Wang, Shi-Fa; Gu, Wen [Journal of the Chinese Chemical Society, 2018, vol. 65, # 5, p. 538 - 547]
[8]Bi, Fangchao; Song, Di; Qin, Yinhui; Liu, Xingbang; Teng, Yuetai; Zhang, Na; Zhang, Panpan; Zhang, Nan; Ma, Shutao [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 14, p. 3179 - 3193]
[9]Hu, Fan; Su, Weike [Journal of Chemical Research, 2020, vol. 44, # 3-4, p. 243 - 247]

5
[ 720-94-5 ]
[ 2863-98-1 ]
4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	In ethanol; for 7h;Reflux;	General procedure: To a warm ethanolic solution (10mL) of 4-hydrazinylbenzonitrile hydrochloride 4 (350mg, 2.0mmol) was added appropriate trifluoromethyl-beta-diketone 5a?5i (2.0mmol) while stirring and the contents were refluxed for 7h. The progress of the reaction was monitored by TLC. When the reaction was completed, excess solvent was evaporated to reduce the volume to one half whereupon reaction mixture was allowed to cool to 20?25°C and the solid thus obtained was filtered to obtain 2a?2i (85?93percent).

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 4581 - 4590
[2]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 4483 - 4487

6
[ 16801-63-1 ]
[ 2863-98-1 ]
[ 918793-02-9 ]

Yield	Reaction Conditions	Operation in experiment
69%	With acetic acid; at 90℃;	Preparation 61; (6-Cyano-2,3,4,9-tetrahydro-lH-carbazol-3-yl)-carbamic acid benzyl esterCombine 4-cyanophenylhydrazine hydrochloride (27.4 g, 162 mmol) and (4- oxo-cyclohexyl)-carbamic acid benzyl ester (Preparation 42) (40.0 g, 162 mmol) in acetic acid (800 mL). Heat the reaction to 90 0C overnight, then cool to room temperature and concentrate under reduced pressure. Triturate the residue in dichloromethane and discard the filter cake. Concentrate the filtrate under reduced pressure. Purify the resulting residue by flash chromatography (silica gel, 9: 1 chloroform:acetone). Recrystillize the resulting material from benzene to provide 38.8 g (69%) of the title compound, m.p. = 141-143 C; mass spectrum (m/e): 344 [C21H19N3O2 - I]'; 1H NMR (300 MHz, CDCl3): 6 8.15 (s, IH), 7.73 (s, IH), 7.29- 7.38 (m, 7H), 5.12 (s, 2H), 4.89-4.92 (m, IH), 4.18 (m, IH), 3.09 (dd, 7= 5.0, 15.5 Hz, IH), 2.78-2.91 (m, 2H), 2.59 (dd, J= 7.0, 15.5 Hz, IH), 2.07-2.17 (m, IH), 1.93-2.05 (m, IH).

Reference： [1]Patent: WO2007/2181,2007,A2 .Location in patent: Page/Page column 168

7
[ 158747-10-5 ]
[ 2863-98-1 ]
[ 2708280-82-2 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In water at 80 - 90℃; for 5h;

Reference： [1]Current Patent Assignee: LIGAND PHARMACEUTICALS INC - US6359146, 2002, B1 Location in patent: Page column 7

8
[ 175277-40-4 ]
[ 2863-98-1 ]
[ 827316-54-1 ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol for 5h; Heating / reflux;	10 Example 10; 4- { (2E)-2- [1- ( H-PYRAZOL-3-YL) ETHYLIDENE] HYDRAZINO} BENZONITRILE A mixture of 3-ACETYLPYRAZOLE HYDROCHLORIDE (0.6 g, 3.5 MMOL) and 4-cyanophenylhydrazine hydrochloride (0.52 G, 3.5 MMOL) in EtOH (4 ml) was heated to boiling for 5 hours. After cooling at 0°C the precipitate was filtered and washed thoroughly with cold ethanol. After drying, the desired hydrazone was obtained as a yellow solid (0.7 g, 88% yield). 1 H-NMR (DMSOd6), diagnostic signals (ppm): 9.82 (s, 1 H), 7.67 (d, 1 H), 7.61 (s, 2H), 7.37 (d, 2H), 6.63 (d, 1 H), 2.31 (s, 3H). [M+H] + =226

Reference： [1]Current Patent Assignee: PFIZER INC - WO2005/5414, 2005, A2 Location in patent: Page 32

9
[ 2863-98-1 ]
[ 102359-00-2 ]
C₁₆H₁₂N₄O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 745 - 750

10
[ 2863-98-1 ]
[ 939-99-1 ]
[ 690248-03-4 ]

Yield	Reaction Conditions	Operation in experiment
43%	Stage #1: 4-hydrazinobenzonitrile hydrochloride With sodium amide In tetrahydrofuran at 0℃; for 1h; Stage #2: 4-trifluoromethylbenzyl chloride In tetrahydrofuran at 0 - 20℃; for 1.5h;	4 EXAMPLE 4N⊃1⊆-(4-trifluoromethylphenylmethyl)-N⊃1⊆-(4-cyanophenyl)hydrazine In a nitrogen atmosphere, powdered sodium amide (95%, 4.8 g, 0.117 mol) was introduced with stirring into a flask containing THF (100 ml). The solution was ice-cooled and 4-cyano-phenylhydrazine hydrochloride (prepared following José L. Castro et al. J. Med. Chem. 1994, 37, 3023-3032) (10 g, 0.058 mol) was added portionwise. The ice bath was removed and a stream of nitrogen was passed through the orange suspension over a period of 1 h to remove most of the dissolved ammonia. With ice-cooling, 4-trifluoromethylbenzyl chloride (12 g, 0.062 mol) was added, then the reaction mixture was stirred at room temperature for 1.5 h and poured into water (100 ml). After extraction with ethyl acetate, the organic layer was washed with water, dried over sodium sulfate and evaporated under vacuum. Trituration from diisopropyl ether gave a yellow solid (7.5 g, 43%), mp 98° C. [00111] 1H-NMR (CDCl3): 3.8 (s, 2H), 4.8 (s, 2H), 7.05 (d, 2H), 7.33 (d, 2H), 7.5 (d, 2H), 7.6 (d, 2H)
	Stage #1: 4-hydrazinobenzonitrile hydrochloride With sodium amide In tetrahydrofuran at 0℃; for 1h; Stage #2: 4-trifluoromethylbenzyl chloride In tetrahydrofuran at 0 - 20℃; for 1.5h;	4 EXAMPLE 4 N1-(4-trifluoromethylphenylmethyl)- N1-(4-cyanophenyl)hydrazine In a nitrogen atmosphere, powdered sodium amide (95%, 4.8 g, 0.117 mol) was introduced with stirring into a flask containing THF (100 ml). The solution was ice-cooled and 4-cyano-phenylhydrazine hydrochloride (prepared following José L.Castro et al. J.Med.Chem. 1994, 37, 3023-3032) (10 g, 0.058 mol) was added portionwise. The ice bath was removed and a stream of nitrogen was passed through the orange suspension over a period of 1 h to remove most of the dissolved ammonia. With ice-cooling, 4-trifluoromethylbenzyl chloride (12 g, 0.062 mol) was added, then the reaction mixture was stirred at room temperature for 1.5 h and poured into water (100 ml). After extraction with ethyl acetate, the organic layer was washed with water, dried over sodium sulfate and evaporated under vacuum. Trituration from diisopropyl ether gave a yellow solid (7.5 g, 43 %), mp 98°C.1H-NMR (CDCl3) : 3.8 (s, 2H), 4.8 (s, 2H), 7.05 (d, 2H), 7.33 (d, 2H), 7.5 (d, 2H), 7.6 (d, 2H)

Reference： [1]Current Patent Assignee: THERAMEX SA - US6737433, 2004, B1 Location in patent: Page/Page column 12
[2]Current Patent Assignee: THERAMEX SA - EP1431292, 2004, A1 Location in patent: Page 10

11
[ 1029691-06-2 ]
[ 2863-98-1 ]
[ 1029691-07-3 ]

Yield	Reaction Conditions	Operation in experiment
66%	With hydrogenchloride; In 1,4-dioxane; acetic acid; at 90 - 100℃; for 36h;	Mix <strong>[1029691-06-2](+/-)-2-(3-oxo-cyclopentyl)-isoindole-1,3-dione</strong> (12.7 g, 55.3 mmol) and 4-cyanophenylhydrazine-HCl (8.53 g, 50.3 mmol) in HOAc (200 mL) and 4N HCl dioxane (50 mL). Using mechanical stirring, heat the reaction to 90 C. for 18 h, then add additional 4N HCl dioxane (20 mL). Heat the reaction to 100 C. for 18 h. Dilute the reaction mixture with water (600 mL) and collect a black solid by vacuum filtration. Sonicate the solid with MeOH (200 mL), then collect and dry in a vacuum oven to give 10.94 g (66%) of a gray-brown solid. MS (m/z): 328 (M+1), 326 (M-1).
66%	With hydrogenchloride; acetic acid; In 1,4-dioxane; at 90 - 100℃; for 36h;	Mix (±)-2-(3-oxo-cyclopentyl)-isoindole- 1 ,3-di- one (12.7 g, 55.3 mmol) and 4-cyanophenylhydrazine-HC1 (8.53 g, 50.3 mmol) in HOAc (200 mE) and 4N HC1 dioxane (50 mE). Using mechanical stirring, heat the reaction to 90 C. for 18 h, then add additional 4N HC1 dioxane (20 mE). Heat the reaction to 100 C. for 18 h. Dilute the reaction mixture with water (600 mE) and collect a black solid by vacuum filtration. Sonicate the solid with MeOH (200 mE), then collect and dry in a vacuum oven to give 10.94 g (66%) of a gray-brown solid. MS (mlz): 328 (M+H), 326 (M-H)

Reference： [1]Patent: US2010/69404,2010,A1 .Location in patent: Page/Page column 12
[2]Patent: US2017/172992,2017,A1 .Location in patent: Paragraph 0037
[3]Journal of Organic Chemistry,2017,vol. 82,p. 5904 - 5909

12
[ 2863-98-1 ]
[ 765-87-7 ]
[ 1259490-42-0 ]

Yield	Reaction Conditions	Operation in experiment
89%	With hydrogenchloride; acetic acid In methanol at 60℃; for 12h;	2 Example 2l-Hydroxy-l-methyl-2,3,4,9-tetrahydro-lH-carbazole-6-carbonitrileIntermediate 2al-Oxo-2,3?4,9-tetrahydro-lH-carbazole-6-carbonitriIe4-Hydrazinylbenzonitrile hydrochloride (3 g, 17.6 mmol) dissolved in MeOH (30 mL), was heated to 60 °C, and 1,2-cyclo hexadione (1.98 g, 17.6 mmol) in AcOH (30 mL) and HC1 (12 mL) were added while maintaining the temperature at 60 °C. The reaction mixture was stirred at 60 °C for 12 h and then cooled to room temperature. The volatiles were removed in vacuo and the residue was diluted with water, neutralized with saturated NaHC03 solution and extracted with EtOAc (2 x 40 mL). The combined organic extracts were concentrated under reduced pressure to give the crude product which was purified by silica gel chromatography [EtOAc- hexane (1 :3) as eluant] to provide the title compound (3.3 g, 89%). 1H NMR (200 MHz, CDC13, δ in ppm) 8.80 (bs, IH), 7.80 (d, J= 2.0 Hz, IH), 7.45 (dd, J= 12.0, 2.0 Hz, IH), 7.30 (d, J= 12.5 Hz, IH), 2.90 (t, J= 9.0 Hz, 2H), 2.62 (t, J= 9.0 Hz, 2H), 2.25 (m, 2H).
7%	With hydrogenchloride; acetic acid In methanol; water at 60℃; for 3h;	16.1 1 -Oxo-2,3 ,4,9-tetrahydro- 1H-carbazole-6-carbonitrile A solution of 4-hydrazineylbenzonitrile hydrochloride (2.04 g, 8.92 mmol) in methanol (20 mL) was added slowly at 60 °C to a mixture of 1,2-cyclohexanedione (2.0 g, 17.84 mmol) inacetic acid (44 mL) and concentrated hydrochloric acid (16 mL). The reaction mixture was stirred for 3 hours at 60 °C. The reaction mixture was diluted with ethyl acetate, and it was washed with water followed by brine. The organic layer was dried over sodium sulfate, and it was concentrated under reduced pressure. The residue was purified on an ISCO chromatograph(0-20% ethyl acetate/hexane) to give the product as a brown solid (130 mg, 7%); ‘H NMR (300MHz) (CDC13) 9.15 (bs, 1H), 8.05 (s, 1H), 7.58 (dd, J= 9 Hz, J= 2 Hz, 1H), 7.49 (d, J 8 Hz,1H), 3.03 (t, J= 6 Hz, 2H), 2.70 (t, J= 6 Hz, 2H), 2.3 5-2.29 (m, 2H).

Reference： [1]Current Patent Assignee: RADIUS HEALTH INC - WO2011/97496, 2011, A1 Location in patent: Page/Page column 35-36
[2]Current Patent Assignee: TAXIS PHARMACEUTICALS INC; RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY - WO2019/5841, 2019, A1 Location in patent: Page/Page column 87; 88

13
[ 109-11-5 ]
[ 2863-98-1 ]
[ 149-73-5 ]
[ 1414773-56-0 ]

Yield	Reaction Conditions	Operation in experiment
94%	Stage #1: morpholine-3-one With trimethoxonium tetrafluoroborate In dichloromethane at 20℃; for 24h; Inert atmosphere; Stage #2: 4-hydrazinobenzonitrile hydrochloride In dichloromethane at 20℃; for 48h; Inert atmosphere; Stage #3: trimethyl orthoformate In chlorobenzene at 130℃; for 24h; Inert atmosphere;

Reference： [1]Massey, Richard S.; Collett, Christopher J.; Lindsay, Anita G.; Smith, Andrew D.; O'Donoghue, Annmarie C. [Journal of the American Chemical Society, 2012, vol. 134, # 50, p. 20421 - 20432]

14
[ 69316-08-1 ]
[ 2863-98-1 ]
[ 1433497-86-9 ]

Yield	Reaction Conditions	Operation in experiment
77%	In methanol;Reflux;	Preparation 63Methyl 4-[5-amino-l-(4-cyanophenyl)pyrazol-3-yl]benzoate Suspend of hydrazinylbenzonitrile hydrochloride (1.86 g, 10.97 mmol) and <strong>[69316-08-1]methyl 4-(2-cyanoacetyl)benzoate</strong> (2.03 g, 9.99 mmol) in MeOH (40 mL). Heat the reaction to reflux while stirring overnight. Cool the reaction mixture to room temperature. Filter the mixture, washing the solid with petroleum ether (40 mL). Dry the resulting solid in vacuo to afford product (2.02 g). Concentrate the filtrate under reduced pressure. Purify the resulting residue by flash chromatography on silica gel (Biotage system, 40 g cartridge (at) 40mL/min) with a gradient of 0-70% EtOAc/DCM (40 min) to afford additional product (0.42 g). Combine the two lots of purified product (2.44 g, 77%). LC- ES/MS m/z 319 [M+H]+.

Reference： [1]Patent: WO2013/66640,2013,A1 .Location in patent: Page/Page column 33

15
[ 582-65-0 ]
[ 2863-98-1 ]
[ 1447577-78-7 ]

Yield	Reaction Conditions	Operation in experiment
85%	In ethanol; for 7h;Reflux;	General procedure: To a warm ethanolic solution (10mL) of 4-hydrazinylbenzonitrile hydrochloride 4 (350mg, 2.0mmol) was added appropriate trifluoromethyl-beta-diketone 5a-5i (2.0mmol) while stirring and the contents were refluxed for 7h. The progress of the reaction was monitored by TLC. When the reaction was completed, excess solvent was evaporated to reduce the volume to one half whereupon reaction mixture was allowed to cool to 20-25C and the solid thus obtained was filtered to obtain 2a-2i (85-93%).

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 4581 - 4590

16
[ 2863-98-1 ]
[ 18931-60-7 ]
[ 1447577-81-2 ]

Yield	Reaction Conditions	Operation in experiment
89%	In ethanol for 7h; Reflux;	1 4.2 General procedure for the synthesis of pyrazoles (2a-2i) in ethanol General procedure: To a warm ethanolic solution (10mL) of 4-hydrazinylbenzonitrile hydrochloride 4 (350mg, 2.0mmol) was added appropriate trifluoromethyl-β-diketone 5a-5i (2.0mmol) while stirring and the contents were refluxed for 7h. The progress of the reaction was monitored by TLC. When the reaction was completed, excess solvent was evaporated to reduce the volume to one half whereupon reaction mixture was allowed to cool to 20-25°C and the solid thus obtained was filtered to obtain 2a-2i (85-93%).

Reference： [1]Chandna, Nisha; Kumar, Satish; Kaushik, Pawan; Kaushik, Dhirender; Roy, Somendu K.; Gupta, Girish K.; Jachak, Sanjay M.; Kapoor, Jitander K.; Sharma, Pawan K. [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 15, p. 4581 - 4590]

17
[ 893-33-4 ]
[ 2863-98-1 ]
[ 1447577-89-0 ]

Yield	Reaction Conditions	Operation in experiment
90%	In ethanol; for 7h;Reflux;	General procedure: To a warm ethanolic solution (10mL) of 4-hydrazinylbenzonitrile hydrochloride 4 (350mg, 2.0mmol) was added appropriate trifluoromethyl-beta-diketone 5a-5i (2.0mmol) while stirring and the contents were refluxed for 7h. The progress of the reaction was monitored by TLC. When the reaction was completed, excess solvent was evaporated to reduce the volume to one half whereupon reaction mixture was allowed to cool to 20-25C and the solid thus obtained was filtered to obtain 2a-2i (85-93%).

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 4581 - 4590

18
[ 52387-36-7 ]
[ 2863-98-1 ]
[ 1527470-83-2 ]

Yield	Reaction Conditions	Operation in experiment
89.6%	With triethylamine In toluene at 0 - 20℃; for 2h;	2 Example 2. Synthesis of (Z)-4-(2-(6-chlorohexylidene)hydrazinyl)benzonitrile To a mixture of 4-cyanophenyihydrazine HCl (3.44 g, 20.3 mlvi) and 6-chlorohexanal (2.5 g, 18.6 mM) in toluene (30 mL) was added triethylamine at 0 °C (2.82 mL, 20.3 mM). The mixture was allowed to stir for 2 hours at ambient temperature. The mixture was filtered and the resultant filter cake was washed with toluene. The combined filtrate was concentrated under vacuum to give 4.92 g of a crude product, which was purified using conventional methods to yield 4.16 g (89.6%) of 4-(2-(6-chlorohexylidene)hydrazinyl)benzonitrile as a mixture of cis trans isomers (ratio 5:1). NMR (400 MHZ, CDCl3): 7.6-6.6 (6H, (4H, dd-aromatic; 1H (m) -NH, 1H (t) - N=CH-t)), 3.57 (2H (t), CH2Cl), 2.2-2.4 (2H (m), =CH-C), 1.75-1.90 (2H (m), CH2Cl- CH2), 1.49-1.65 (4H (m), CH2-CH2); mlz: 250 [M + Hj+, calcd for [C13H16ClN3+ H]+ 250.10.

Reference： [1]Current Patent Assignee: ABBVIE INC - WO2014/5134, 2014, A2 Location in patent: Paragraph 0064

19
[ 52387-36-7 ]
[ 2863-98-1 ]
[ 1527470-88-7 ]

Yield	Reaction Conditions	Operation in experiment
35 g	Stage #1: 6-chlorohexanal With sulfuric acid In methanol; water at 20℃; for 0.333333h; Stage #2: 4-hydrazinobenzonitrile hydrochloride In methanol; water at 20℃;	2 Preparation of 4-[(2E)-2-(6- chlorohexylidene)hydrazinyl]benzonitrile (compound of formula XIII) Water (250mL) was added to a solution of 6-chlorohexanal (23.8g, G.176mol) prepared as in Example 1 , in methanol (250mL) at about room temperature. The reaction mixture was stirred for about lOmin and then sulphuric acid (lOg, 0.102mol) was slowly added at about room temperature. The reaction mass was stirred for about lOmin and 4- cyanophenylhydrazine hydrochloride (25g, 0.147mol) was added lot wise at about room temperature. After completion of reaction, the precipitated solid was filtered, washed with water; dried at about 50°C to about 55°C for about 12h to give 35g of 4-[(2£)-2-(6- chlorohexylidene)hydrazinyl]benzonitrile.

Reference： [1]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2014/87428, 2014, A1 Location in patent: Paragraph 0145; 0153

20
[ 67751-23-9 ]
4-cyanophenylhydrazine hydrochloride salt [ No CAS ]
4-(5-formyl-1H-pyrazol-1-yl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34%	With hydrogenchloride; In ethanol; at 78℃; for 3.5h;	Step 2 4-(5-formyl-1H-pyrazol-1-yl)benzonitrile A solution of 4-hydrazinylbenzonitrile hydrochloride (10.14 g, 59.78 mmol, 1.00 equiv), <strong>[67751-23-9](E)-4-(dimethylamino)-1,1-dimethoxybut-3-en-2-one</strong> (17.6 g, 101.61 mmol, 1.70 equiv), propan-2-one (30 mL) and 6N hydrochloric acid (30 mL) in ethanol (300 mL) was stirred at 78 C. for 3.5 h. The resulting mixture was cooled to room temperature and concentrated under vacuum. Water (300 mL) and ethyl acetate (200 mL) were added to dissolve the residue. The resulting mixture was extracted with ethyl acetate (2200 mL). The combined organic layers was washed with water (1100 mL) and brine (1*100 mL), dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with 0-20% of ethyl acetate in petroleum ether to give 4 g (34%) of 4-(5-formyl-1H-pyrazol-1-yl)benzonitrile as a yellow solid. 1H-NMR (300 MHz, CDCl3): delta 9.87 (s, 1H), 8.09-7.98 (m, 3H), 7.85-7.83 (m, 2H), 7.36 (d, J=1.5 Hz, 1H) ppm. LCMS (method A, ESI): RT=1.28 min, m/z=198.0 [M+H]+.

Reference： [1]Patent: US2014/315961,2014,A1 .Location in patent: Paragraph 0322-0323

21
[ 52387-36-7 ]
[ 2863-98-1 ]
[ 143612-79-7 ]

Yield	Reaction Conditions	Operation in experiment
162 g	With sulfuric acid; In ethanol; water; at 80℃; for 4h;	Compound 11 (169 g, 1 mol) was dissolved in EtOH/H2O (1:1, 100mL), and then, 20% H2SO4 (20 mL) and 6-chlorohexanal 12 (134g, 1.0 mol) were added. The mixture was stirred at 80C for 4 h. After the reaction was complete, the aqueous was extracted with CH2Cl2. The combined CH2Cl2 fractions were evaporated to afford product 3 as a milky-white solid. Yield 162g (70%), 97% purity. m.p. 97.6-99.5C. (Lit1 99-99.5C) 1H NMR (400MHz, DMSO-d6): delta 11.38 (s, 1H), 8.08 (s, 1H), 7.55-7.25 (m, 3H), 3.67 (t, J =6.1Hz, 2H), 2.75 (t, J= 6.7Hz, 2H), 1.77 (dd, J=6.3, 3.1Hz, 4H). 13C NMR (100MHz, DMSO-d6): delta 137.8, 127.2, 124.8, 124.5, 123.2, 120.7, 117.1, 111.9, 102.2, 44.9, 32.4, 27.3, 24.2. HRMS (ESI): m/z [M+Na]+ calculated for C13H13ClN2: 255.0659, found: 255.0657.

Reference： [1]Synthetic Communications,2014,vol. 44,p. 3563 - 3571
[2]Journal of Chemical Research,2020,vol. 44,p. 243 - 247

22
[ 52387-36-7 ]
[ 2863-98-1 ]
4-(2-(6-chlorohexylidene)hydrazinyl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With sulfuric acid In N,N-dimethyl acetamide; water at 25 - 35℃; for 1h;	Synthesis of 3-(4-Chlorobutyl)-1H-indole-5-carbonitrile (2a) General procedure: Aldehyde 4a/4b (0.35 mol) was added to a solution of 4-cyanophenyl hydrazine hydrochloride 3 (50.0 g, 0.29 mol) in 4% H2SO4(aqueous) (250 ml) and DMAc (250 ml). The reaction mixture was stirred for 1.0 h at 25-35 °C, and product 5a/5b was extracted into toluene (500 ml); 85% H3PO4(aqueous) (170 g, 0.147 mol) was added to the toluene layer, refluxed for 3.0 h, and then cooled to ambient temperature. The organic phase was separated, washed with 1.2M NaHCO3(aqueous) (500 ml) and water (500 ml), and evaporated under vacuum. The crude obtained was recrystallized from ethyl acetate and hexane solvent system. Yield: 74.0%; purity by HPLC: 98.0%.

Reference： [1]Anitha; Reddy, B. Sudhakar; Sekhar; Reddy, K. Venugopal; Chandrasekhar [Synthetic Communications, 2014, vol. 44, # 24, p. 3563 - 3571]

23
[ 2863-98-1 ]
[ 979-02-2 ]
3β-acetoxyandrosta-5,16-dien-20-one 4'-cyanophenylhydrazone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium acetate In methanol for 1.5h; Reflux;	6 4.2.1 General procedure for the synthesis of steroidal hydrazones (3a-h) and semicarbazone (3i) General procedure: Compound 1 (713mg, 2.00mmol) was suspended in MeOH (10mL), and the appropriate arylhydrazine or semicarbazide hydrochloride (2a-g or 2i) (2.50mmol) and anhydrous NaOAc (205mg, 2.50mmol) or methylhydrazine (2h, 0.26mL, 5.00mmol) and a catalytic amount (2 drops) of AcOH were added, and the mixture was refluxed for 90min. The resulting precipitate was filtered off (except in the case of 3h, which was transformed directly after evaporation of the solvent), washed with a small amount of ice-cold MeOH and dried to give the crude arylhydrazone (3a-g) or semicarbazone (3i).

Reference： [1]Kovács, Dóra; Wölfling, János; Szabó, Nikoletta; Szécsi, Mihály; Schelz, Zsuzsanna; Zupkó, István; Frank, Éva [European Journal of Medicinal Chemistry, 2016, vol. 120, p. 284 - 295]

24
[ 141-86-6 ]
[ 2863-98-1 ]
2,6-diamino-3-(4'-cyanophenyl)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With potassium carbonate In dimethyl sulfoxide at 25℃; for 24h; regioselective reaction;	4.2. General procedure for the arylation of aminoheterocycles with arylhydrazine hydrochlorides General procedure: A mixture of the arylhydrazine hydrochlorides (1.0 mmol), aminopyridines (20.0 mmol), and potassium carbonate (415 mg, 3.0 mmol) in DMSO (10 mL) was stirred at 25 °C in air. The reactions were completed after 24 h, monitored by thin layer chromatography (TLC). Then, quenched by the addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water and brine solution and dried over anhydrous MgSO4. The solvent was removed under reduced pressure to give the crude products. Purified by column chromatography over silica gel (hexane/AcOEt), the pure products were afforded.

Reference： [1]Taniguchi, Toshihide; Imoto, Mitsutaka; Takeda, Motonori; Matsumoto, Fukashi; Nakai, Takeo; Mihara, Masatoshi; Mizuno, Takumi; Nomoto, Akihiro; Ogawa, Akiya [Tetrahedron, 2016, vol. 72, # 27-28, p. 4132 - 4140]

25
[ 52387-36-7 ]
[ 2863-98-1 ]
[ 1527470-88-7 ]
[ 1527470-83-2 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In methanol at 0 - 5℃; for 0.25h; Inert atmosphere; Overall yield = 84 %; Overall yield = 26.6 g;	1 Example 1 Synthesis of 6-chlorohexanal-4-cyanophenylhydrazone A solution of 21.40 g (0.126 mol) of 4-cyanophenylhydrazine hydrochloride in 250 mL of a three-necked flask was added with 140 mL of methanol and 13.40 g of Et3N (0.133 mol) under dry N2 protection. Ice bath cooling, was added dropwise chlorohexanal (23.30 g, 0.174 mol) at 0 to 5 ° C, after completion of the dropwise addition, the mixture was stirred at that temperature, after about 15 minutes, the reaction was complete by TLC (petroleum ether: ethyl acetate = 1: 1) and the reaction was stopped. The reaction solution was poured into ice water and stirred at -10 to 0 ° C. A solid precipitated, which was filtered and dried in vacuo to give 26.6 g of hydrazone in 84% yield. The obtained hydrazone is a mixture of cis and trans isomers, the ratio of the two is 1: 4, the cis structure identification data are as follows:

Reference： [1]Current Patent Assignee: BEIJING CHIRAL TECH PHARMACEUTICAL TECH - CN105601536, 2016, A Location in patent: Paragraph 0027; 0028; 0029; 0030; 0031; 0032

26
[ 34846-90-7 ]
[ 2863-98-1 ]
1-(4-cyanophenyl)-5-hydroxypyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64.2%	In methanol; for 6h;Reflux;	1.70 g (10 mmol) of 4-cyanophenylhydrazine hydrochloride, 1.16 g (10 mmol) of methoxypropan-2-ol were added to a three-necked reaction flaskMethylene chloride, 10 mL of methanol. The temperature of the reaction mixture was raised to reflux for about 6 hours. The reaction solution was quantitated by liquid chromatography, and 1- (4-cyanoPhenyl) -5-hydroxypyrazole Yield 64.2percent

Reference： [1]Patent: CN104059020,2016,B .Location in patent: Paragraph 0028; 0029

27
[ 2863-98-1 ]
[ 92886-57-2 ]
[ 143612-79-7 ]

Yield	Reaction Conditions	Operation in experiment
8 g	In methanol; water; at 70 - 72℃; for 1h;Inert atmosphere;	A solution of 6.5 g of 1-dimethoxy-6-chlorohexane was dissolved in 65 mL of methanol and 35 mL of water under a nitrogen atmosphere at room temperature, and the temperature was increased to 70 C to dissolve the whole solution. 4-cyanobenzene hydrazine hydrochloride 60 mL of methanol and 30 mL of pure water was slowly added dropwise to a solution of 5.9 g of 1,1-dimethoxy-6-chlorohexane in the reaction mixture at room temperature. At 72 C, under the conditions of insulation 1.0 hours, until the reaction solution to room temperature, precipitation of a large number of solid, filter, filter cake with 53% ethanol solution of recrystallization. To give 8.0 g of 3-(4-chlorobutyl)-5-cyanoindole.
9.5 g	In methanol; water; at 72℃; for 1h;Inert atmosphere;	At room temperature,5.2 g.l-dimethoxy-6-chlorohexane was dissolved in 52 mL of methanol and 26 mL under nitrogenWater mixed solution,Raise to 72 C to dissolve all.At room temperature,4.8 g of 4-cyanophenylhydrazine hydrochloride,48 mL of methanol and 24 mL of pure water was slowly added dropwise to a solution of 4.6 g of 1-dimethoxy-6-chlorohexane,At 72 CUnder the insulation of 1.0 hours, until the reaction solution to room temperature, precipitation of a large number of solid, filter, filter cake with 53% ethanol aqueous solution to recrystallize,To give 9.5 g of 3- (4-chlorobutyl) -5-cyanoindole.

Reference： [1]Patent: CN103360374,2016,B .Location in patent: Paragraph 0041; 0055
[2]Patent: CN103360373,2016,B .Location in patent: Paragraph 0030; 0044; 0046

28
[ 34035-03-5 ]
[ 2863-98-1 ]
4-(2-[(5-(4-chlorophenyl)furan-2-yl)methylene]-hydrazinyl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	In ethanol; for 6h;Reflux;	General procedure: A mixture of 4-cyanophenylhydrazine hydrochloride (3 mmol) and 5-arylfurfural (3 mmol) in absolute ethanol (20 mL) was refluxed for 6 hours. The resulting solid was filtered and crystallized from ethanol. 2.2.1.1. 4-[2-((5-(4-Chlorophenyl)furan-2-yl)methylene)hydrazinyl] benzonitrile (1) [16] M.p. 229-230C. Yield 90%. IR numax (cm-1): 3278.99, 3151.69, 3062.96, 2918.30, 2848.86, 2204.64, 1602.85, 1577.77, 1541.12, 1517.98, 1473.62, 1425.40, 1408.04, 1346.31, 1317.38, 1276.88, 1217.08, 1170.79, 1138.00, 1124.50, 1103.28, 1091.71, 1056.99, 1008.77, 921.97, 902.69, 879.54, 823.60, 810.10, 781.17. 1H NMR (400 MHz, DMSOd6) delta (ppm): 6.92 (d, J= 3.6 Hz, 1H), 7.15-7.17 (m, 3H), 7.52 (d, J= 8.4 Hz, 2H), 7.65 (d, J= 8.4 Hz, 2H), 7.80 (d, J= 8.8 Hz, 2H), 7.90 (s, 1H), 11.04 (s, 1H). 13C NMR (100 MHz, DMSO-d6) delta (ppm): 99.49 (C), 108.94 (2CH), 112.11 (2CH), 113.38 (2CH), 120.04 (C), 125.28 (2CH), 128.54 (C), 129.01 (2CH), 132.21 (C), 133.63 (CH), 148.21 (C), 150.05 (C), 152.47 (C). HRMS (ESI) (m/z): [M M+H]+ calcd. for C18H12ClN3O: 322.0742, found: 322.0737.

Reference： [1]Letters in drug design and discovery,2020,vol. 17,p. 312 - 322
[2]Archiv der Pharmazie,2016,vol. 349,p. 112 - 123

29
[ 328-42-7 ]
[ 2863-98-1 ]
1-(4-cyanophenyl)-5-hydroxy-pyrazole-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	In acetic acid for 1h; Reflux;	1-(4-Cyanophenyl)-5-hydroxy-pyrazole-3-carboxylic acid9, A suspension of oxaloacetic acid (780 mg, 5.9 mmol) and 4-cyanophenylhydrazine hydrochloride (1 g, 5.9 mmol) in acetic acid (15 mL) was heated to reflux for 1 h. The reaction mixture was cooled to room temperature, and then water (20 mL) was added. The resulting white precipitate was collected by filtration and dried to afford the title compound (1.26 g, 93%) as a white powder.1H NMR (300 MHz, DMSO-d6) δ 12.63 (br s, 1H), 12.32 (br s, 1H), 8.11-7.89 (m, 4H), 5.95 (s, 1H). LC-MS: (Low pH) tR0.71 min,m/z228.1 [M-H]-, 100% purity.

Reference： [1]Mould, Daniel P.; Bremberg, Ulf; Jordan, Allan M.; Geitmann, Matthis; Maiques-Diaz, Alba; McGonagle, Alison E.; Small, Helen F.; Somervaille, Tim C.P.; Ogilvie, Donald [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 14, p. 3190 - 3195]

30
[ 2863-98-1 ]
[ 94-05-3 ]
[ 1152932-52-9 ]

Yield	Reaction Conditions	Operation in experiment
94%	In ethanol at 80℃; for 12h;
80%	With triethylamine In ethanol at 20 - 80℃; for 8h;	4.2.2 Ethyl 5-amino-1-(4-methoxyphenyl)-1H-pyrazole-4-carboxylate (2b) General procedure: To ethyl 2-cyano-3-ethoxyacrylate (2.00 g, 11.8 mmol) and 4-methoxyphenyl hydrazine hydrochloride (2.06 g, 11.8 mmol) in ethanol (75 mL) at room temperature was added triethylamine (1.65 mL, 11.8 mmol). The mixture was stirred at 80 °C for 8 h. After cooling the reaction mixture to room temperature, ethanol was removed in vacuo and the residue was partitioned between ethyl acetate and water. The organic layer was dried over magnesium sulfate. The solvent was evaporated in vacuo and the residue was chromatographed on a silica gel column with a mixture of n-hexane and ethyl acetate (3:1) to give the desired product 2b (2.42 g, 78 %). 1H NMR (300 MHz, CDCl3): δ=7.76 (s, 1H), 7.42 (d, J=6.9Hz, 2H), 7.01 (d, J=6.9Hz, 2H), 5.19 (br s, 2H), 4.30 (q, J=7.1Hz, 2H), 3.82 (s, 3H), 1.36 (t, J=7.1Hz, 3H) ppm; MS (ESI): m/z: 262 [M+H+].

Reference： [1]Carlson, David A.; Singer, Miriam R.; Sutherland, Cindy; Redondo, Clara; Alexander, Leila T.; Hughes, Philip F.; Knapp, Stefan; Gurley, Susan B.; Sparks, Matthew A.; MacDonald, Justin A.; Haystead, Timothy A.J. [Cell Chemical Biology, 2018, vol. 25, # 10, p. 1195 - 32,1207]
[2]Heo, Yun-Jeong; Jeon, Moon-Kook [Tetrahedron, 2017, vol. 73, # 40, p. 5959 - 5973]

31
[ 2863-98-1 ]
[ 622-88-8 ]
[ 1591-30-6 ]
[ 57774-35-3 ]
[ 92-86-4 ]

Reference： [1]RSC Advances,2014,vol. 4,p. 43336 - 43340

32
[ 27996-87-8 ]
[ 2863-98-1 ]
C₁₄H₉FN₄O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	In N,N-dimethyl-formamide; at 50℃; for 2h;Inert atmosphere;	General procedure: To a stirred solution of the carbonyl compound (1.0 mmol) in DMF (5 mL) at 50 C (oil bath)was added ArNHNH2.HCl (3.0 mmol for 5, 2.0 mmol for 6) and the solution was stirred until TLC(20% EtOAc in hexanes) indicated complete conversion (roughly 2 h). The crude reaction mixture wasadded to water and extracted with EtOAc (2 Chi 15 mL). The combined organic layers were washedwith water and saturated aq NaCl, dried (MgSO4), filtered, and concentrated under vacuum to givethe crude hydrazones. The crude products were stirred with 20% ether/pentane for 1 h, filtered anddried to give arylhydrazones 9 and 10. Characterization data for these materials are given in the ESI.

Reference： [1]Molecules,2018,vol. 23

33
[ 66-98-8 ]
[ 2863-98-1 ]
C₂₈H₂₀N₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	With hydrogenchloride; In ethanol; water; at 80℃; for 0.5h;Inert atmosphere;	To a solution of [1,1'-biphenyl]-4,4'-dicarboxaldehyde (100 mg, 0.48 mmol) inEtOH (5 mL), 4-cyanophenylhydrazine hydrochloride(201 mg, 1.19 mmol) and a catalytic amount of concentrated HCl (0.04 mL) were added. The reaction mixture was stirred at 80 C for 30 min and the resulting solution was filtered. The residue obtained was washed with hot EtOH (25 mL) to afford compound 13b (142 mg, 67%) as a yellow solid: 1H NMR (400 MHz, (CD3)2SO, Fig. S17) delta 10.99 (s, 2H), 7.98 (s, 2H), 7.77 (d, J = 8.8 Hz,4H), 7.74 (d, J = 8.8 Hz, 4H), 7.60 (d, J = 8.8 Hz, 4H), 7.15 (d, J = 8.8 Hz, 4H), 13C NMR (100MHz, (CD3)2SO, Fig. S18) delta 149.0, 140.04, 140.00, 134.8, 134.1, 127.3, 127.2, 120.5, 112.6, 99.8.

Reference： [1]European Journal of Medicinal Chemistry,2019,vol. 164,p. 273 - 281

34
[ 22078-59-7 ]
[ 2863-98-1 ]
4-[2-((5-(3-chlorophenyl)furan-2-yl)methylene)hydrazinyl]benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	In ethanol for 6h; Reflux;	2.2.1. 4-[2-((5-Arylfuran-2-yl)methylene)hydrazinyl]benzonitrilederivatives (1-10) General procedure: A mixture of 4-cyanophenylhydrazine hydrochloride (3 mmol) and 5-arylfurfural (3 mmol) in absolute ethanol (20 mL) was refluxed for 6 hours. The resulting solid was filtered and crystallized from ethanol.

Reference： [1]Baysal, Merve; Demirel, Rasime; Sever, Belgin; Özdemir, Ahmet; Altıntop, Mehlika Dilek; Eklioğlu, Özlem Atlı [Letters in drug design and discovery, 2020, vol. 17, # 3, p. 312 - 322]

35
[ 2863-98-1 ]
[ 118431-88-2 ]
4-(5-amino-3-cyclopropyl-1H-pyrazol-1-yl)benzonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With hydrogenchloride; In ethanol; for 20h;Reflux;	General procedure: A stirred solution of the hydrazine hydrochloride (1 eq), β-ketonitrile (1 eq) and a drop of HCl (conc.) in EtOH (10 mL) was heated at reflux for 18 h. After cooling to rtrt, the mixture was basified to pH 12 by the addition of an aqueous NaOH solution (10%) (compound 6) or a sat. NaHCO3 solution (compounds 10-17) and extracted with EtOAc (3 x30 mL). The organic extracts were combined, washed with brine (40 mL), dried over Na2SO4 and the solvent was evaporated in vacuo. Purification by flash column chromatography on SiO2 or recrystallization from a hexane/EtOAc mixture gave the desired product.

Reference： [1]European Journal of Medicinal Chemistry,2020,vol. 208

36
[ 328-42-7 ]
[ 64-17-5 ]
[ 2863-98-1 ]
ethyl 1-(4-cyanophenyl)-5-hydroxy-pyrazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71.2%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.
71.2%	at 85℃; for 12h;	4.1.1. 5-methyl-1-(4-((N-methylsulfiiamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylic acid (12a) General procedure: Step 2. To a solution of 8a (118 mg, 1 mmol) and 4-hydrazino-N-methylbenzenemethanesulfonamide hydrochloride (9, 252 mg, 1 mmol) in anhydrous ethanol (10 mL) was stirred at 85 °C overnight. The reaction was allowed to cool to room temperature and concentrated. The crude material was purified by Isolera Biotage LPLC (PE/EA = 30%) to give a mixture of methyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (10a) and ethyl 5-methyl-1-(4-((N-methylsulflamoyl)methyl)phenyl)-1H-pyrazole-3-carboxylate (11a) as a white solid.

Reference： [1]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]
[2]Fan, Yan; Fang, Zhen; Guo, Nihong; Guo, Yinping; Li, Linli; Liu, Yang; Mu, Bo; Xia, Anjie; Xiang, Rong; Xiong, Liang; Yang, Shengyong; Yao, Rui; Zhang, Hailin; Zhang, Rong [European Journal of Medicinal Chemistry, 2022, vol. 238]

37
[ 2863-98-1 ]
[ 78-93-3 ]
[ 36798-23-9 ]

Yield	Reaction Conditions	Operation in experiment
77%	With glacial acetic acid at 110℃; for 23h; Inert atmosphere;

Reference： [1]Ryckaert, Bram; Hullaert, Jan; Van Hecke, Kristof; Winne, Johan M. [Organic Letters, 2022, vol. 24, # 23, p. 4119 - 4123]

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Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 2863-98-1 ] {[proInfo.proName]}

Quality Control of [ 2863-98-1 ]

Related Doc. of [ 2863-98-1 ]

Product Details of [ 2863-98-1 ]

Calculated chemistry of [ 2863-98-1 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 2863-98-1 ]

Application In Synthesis of [ 2863-98-1 ]

[ 2863-98-1 ] Synthesis Path-Upstream 1~4

[ 2863-98-1 ] Synthesis Path-Downstream 1~37

Related Functional Groups of [ 2863-98-1 ]

Aryls

Amines

Hydrazines

Nitriles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 2863-98-1 ]