Name: 127892-62-0|4-Chloro-3-ethyl-1-methyl-1H-pyrazole-5-carboxylic acid|97%
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SKU: A222021
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1
[ 509101-25-1 ]
[ 127892-62-0 ]
[ 509098-50-4 ]

Yield	Reaction Conditions	Operation in experiment
74%	With sodium hydrogencarbonate In DMF (N,N-dimethyl-formamide) at 100℃; for 7h;	5 Production Example 5; Production of compound (26) by the production method 1 Production Example 5; Production of compound (26) by the production method 1; To 10 ml of N,N-dimethylformamide were dissolved 0.50 g (2.2 mmol) of 6, 6-difluoro-5-methyl-5-hexenyl methanesulfonate and 0.45 g (2.4 mmol) of 4-chloro-5-ethyl-2-methyl-2H-pyrazole-3-carboxylic acid, followed by the addition of 0.37 g (4.4 mmol) of sodium hydrogencarbonate and stirring at 100 °C for 7 hours. The reaction liquid was then poured in water and extracted with ethyl acetate. The organic layer was washed with water and a saturated saline solution in this order, followed by drying over anhydrous magnesium sulfate and concentration under reduced pressure. The residue was purified with silica gel column chromatography (ethyl acetate:hexane=1:19) to obtain 0.52 g (yield: 74 %) of 6,6-difluoro-5-methyl-5-hexenyl 4-chloro-5-ethyl-2-methyl-2H-pyrazole-3-carboxylate.1H-NMR (CDCl3, TMS) δppm: 1.24 (3H, t), 1.54-1.64 (5H, m), 1.71-1.80 (2H, m), 2.01-2.07 (2H, m), 2.65 (2H, q), 4.10 (3H, s), 4.34 (2H, t)

Reference： [1]Current Patent Assignee: KUMIAI CHEMICAL INDUSTRY CO LTD - EP1439169, 2004, A1 Location in patent: Page 76-77

2
[ 127892-62-0 ]
[ 1059622-49-9 ]
[ CAS Unavailable ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.166667h;	2 Synthesis of 5-N-(4-tert-butyl-3-[18F]fluoro)benzylcarboxamido-4-chloro-3-ethyl-1-methylpyrazoline Synthesis of 5-N-(4-tert-butyl-3-[18F]fluoro)benzylcarboxamido-4-chloro-3-ethyl-1-methylpyrazoline To a stirred mixture of 3-ethyl-1-methylpyrazole-5-carboxylic acid (50 umole), dicyclohexylcarbodiimide (DCC, 50 umole, delivered as an aliquot from a stock solution in dichloromethane), hydroxybenzotriazole (HOBt, 60 umole) in methylene chloride (200 uL), is added a solution of 4-tert-butyl-3-[18F]fluorobenzylamine (prepared above) in dichloromethane (100 uL). The mixture is stirred at room temperature for ten minutes at room temperature, concentrated and dissolved in acetonitrile-water (1:4, 3 mL). The mixture is passed through a silica gel cartridge (pre-loaded Waters Light C-18 Sep-Pak) to load the sample. The cartridge is rinsed with water and eluted with CH3CN (2 mL). The acetonitrile is evaporated and the residue is purified via HPLC to afford pure carrier-free 5-N-(4-tert-butyl-3-[18F]fluoro)benzylcarboxamido-4-chloro-3-ethyl-1-methylpyrazoline.

Reference： [1]Current Patent Assignee: LANTHEUS MI HOLDINGS INC - US2005/191238, 2005, A1 Location in patent: Page/Page column 49

3
[ 127892-62-0 ]
[ 3091-32-5 ]
[ 355005-38-8 ]

Yield	Reaction Conditions	Operation in experiment
36%	With potassium hydroxide In toluene byproducts: KCl; under dry Ar, 1 equiv. of KOH and pyrazole-compd. were stirred in toluene for 4 h at room temp., 1 equiv. of Sn-compd. was added, stirring overnight at room temp.; solvent was removed in vac., solid was recrystd. from CH2Cl2/petroleum ether (1:3, v/v), dried in vac., elem. anal.;

Reference： [1]Li, Jinshan; Zhao, Guofeng; Xiong, Chuanhui; Ma, Yongqiang [Synthesis and Reactivity in Inorganic and Metal-Organic Chemistry, 2001, vol. 31, # 1, p. 85 - 93]

4
[ 127892-62-0 ]
[ 639-58-7 ]
[ 355005-35-5 ]

Yield	Reaction Conditions	Operation in experiment
83.8%	With potassium hydroxide In toluene byproducts: KCl; under dry Ar, 1 equiv. of KOH and pyrazole-compd. were stirred in toluene for 4 h at room temp., 1 equiv. of Sn-compd. was added, stirring overnight at room temp.; solvent was removed in vac., solid was recrystd. from CH2Cl2/petroleum ether (1:3, v/v), dried in vac., elem. anal.;

Reference： [1]Li, Jinshan; Zhao, Guofeng; Xiong, Chuanhui; Ma, Yongqiang [Synthesis and Reactivity in Inorganic and Metal-Organic Chemistry, 2001, vol. 31, # 1, p. 85 - 93]

5
[ 127892-62-0 ]
[ 129560-00-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	With dichloro sulfoxide In toluene for 4.08333h; Reflux;	1.1 Synthesis of 4-chloro-3-ethyl-1-methylpyrazole-5-formyl chloride To 250mLThe reaction flask was added4-chloro-3-ethyl-1-methylpyrazole-5-carboxylic acid 18.85 g (0.1 mol)100 g of toluene was added,Stir for 5min,23.8 g (0.2 mol) of thionyl chloride was added dropwise,Slowly heat up to reflux.Reflux reaction 4h,The toluene and excess thionyl chloride were removed by distillation under reduced pressure,Obtained 20.70 g of a reddish brown oil in 100% yield
99%	With dichloro sulfoxide In toluene at 80℃; for 3h;	1.1 Toluene as a solvent,Compound G and 0.03 mol (3.57 g)Thionyl chloride is added to the reaction flask,Reaction at 80 ° C for 3 h,TLC tracking reaction is complete,Rotary to remove toluene,Compound IIIa 5.11g,The yield was 99%.
93.8%	With dichloro sulfoxide; N,N-dimethyl-formamide In toluene at 20 - 60℃; for 7h;

90%	With dichloro sulfoxide; N,N-dimethyl-formamide In 1,2-dichloro-ethane for 5h; Reflux;	10.1 The first step reaction: Preparation of 4-chloro-3-ethyl-1hydro-pyrazole-4-acid chloride: At room temperature, add 4-chloro-3-ethyl-1hydro-pyrazole-4-carboxylic acid (1.88g, 0.01mol), dichloroethane (20ml) and N, N-dimethylformamide (0.05 g) Add to a three-necked flask, and add dichlorosulfoxide (2.02 g, 0.02 mol) to the above mixture dropwise. Heat to reflux for 5 hours. The heating was stopped and the solvent and residual dichlorosulfoxide were removed under reduced pressure to obtain 1.86 g of product with a yield of 90%.
	With dichloro sulfoxide
	With dichloro sulfoxide for 1h; Reflux;
	With dichloro sulfoxide at 76℃; for 7h; Inert atmosphere;
	With dichloro sulfoxide for 4h; Reflux;
	With dichloro sulfoxide for 1h; Reflux;
35 g	With phosgene In 1,2-dichloro-ethane for 6h; Reflux;	1.1 (1) Synthesis of 1-methyl-3-ethyl-4-chloro-5-pyridinecarbonyl chloride To a 250 mL reaction flask was added 30.0 g (0.156 mol) of the compound of formula II and 60 mL of dichloroethane, dropwise with stirringA solution of 23.0 g (0.078 mol) of triphosgene (i.e., solid phosgene) and 60 mL of dichloroethane was added and the mixture was heated to refluxThe reaction mixture was cooled for 6 hours, and the solvent was removed to give 35 g of Compound III as an oil.
	With dichloro sulfoxide In 1,2-dichloro-ethane for 4h; Reflux;
	With dichloro sulfoxide Reflux;	1 With a magnetic stirrer,1-methyl-3-ethyl-4-chloro-5-pyrazolecarboxylic acid (1.88 g, 10 mmol) was added to a three-Thionyl chloride (15 mL),Heated to reflux for 4-6 hr,Remove the organic solvent after the standby.
	With dichloro sulfoxide In toluene for 1h; Reflux;	A 100 ml round bottom flask was added N-methyl-3-ethyl-4-chloropyrazoleic acid (0.02 mol, 3.77 g)SOCl2 (0.12 mol, 16.2 g) was stirred at reflux for 1 h,Evaporation of excess SOCl2 was added to 10 ml of toluene.
	With dichloro sulfoxide In 1,2-dichloro-ethane for 2h; Reflux;	Synthesis of 1,3-dimethyl-1H-pyrazole acyl chloride (4a) and its analogues (4b-p) General procedure: 3a (0.01 mol) and thionyl chloride (2.95 g, 0.025 mol) were successively added to 15 ml 1,2-dichloroethane. After 2 h under reflux, the solvent was removed under reduced pressure. 4a was obtained and without further purification and calculating the yield, next reaction was carried out immediately. The analogues 4b-p were prepared in a similar procedure.
	With dichloro sulfoxide for 2h; Reflux;	General Procedure for the Synthesis of Compound 6a~6n 4-chloro-3-ethyl-1-methyl-1H-pyrazole-5-carboxylic acid was synthesized according to reference [17]. To a solution of SOCl2 (10 mL), 4-chloro-3-ethyl-1-methyl-1H-pyrazole-5-carboxylic acid (10 mmol) was added in batches, then the mixture was refluxed for 2h to give the acyl chloride.
	With dichloro sulfoxide In 1,2-dichloro-ethane; N,N-dimethyl-formamide for 3h; Reflux;	General procedure: Pyrazole acid 9a-k (3 mmol) and thionyl chloride (7.5 mmol)were successively added to 20 mL 1,2-dichloroethane, the mixturewere stirred under reflux for 3 h and then concentrated underreduced pressure, the crude products were added in drops into asolution of 5′a-f (5a-h) (3 mmol) and trimethylamine (6 mmol) inTHF (15 mL).The reaction mixturewas stirred under the 0 C for thenight. After reaction the mixture was poured in Na2CO3 solutionand aqueous phase was extracted with ethyl acetate (2 20 mL).The combined organic phase was washed with saturated salt water(2 20 mL), dried over anhydrous Na2SO4, and concentrated underreduced pressure and the residue was purified by silica gel columnchromatography
15.8 g	With dichloro sulfoxide In 1,2-dichloro-ethane at 35℃; Reflux;	1 1-methyl-3-ethyl-4-chloropyrazole-5-carbonyl chloride 1-methyl-3-ethyl-4-chloropyrazole-5-carboxylic acid(100 mmol), thionyl chloride (150 mmol) and 1,2-dichloroethane (100 mL) at 35 °C to system reflux temperature Reaction 3 -After 5 hours, the solvent was removed to give 15.8 g of the title compound.
	With dichloro sulfoxide Reflux;	1.1 1) Synthesis of 4-chloro-3-ethyl-1-methyl-5-pyrazolecarbonyl chloride 2.3 g (12.0 mmol) of 4-chloro-3-ethyl-1-methyl-5-pyrazolecarboxylic acid was added to a 100 ml one-mouth reaction flask.20 ml of thionyl chloride, then heated to reflux,Until the solid disappears completely, continue to reflux for 2 to 3 hours.Rotary steamerThe solvent was dehydrated, dissolved in a small amount of methyl tert-butyl ether, and then spun dry, and the excess thionyl chloride was removed as much as possible. Of courseAfter adding a certain amount of methyl tert-butyl ether, it was dissolved and used for the next step.
	With dichloro sulfoxide In toluene Reflux;	1.3 (3) Synthesis of 4-chloro-3-ethyl-1-methyl-1H-pyrazole-5-carbonyl chloride In a 250 mL three-necked flask, add 0.03 mol (5.65 g) of 4-chloro-3-ethyl-1-methyl-1H-pyrazole-5-carboxylic acid,Add 50mL toluene as solvent.Weigh 0.045mol (5.35g) in thionyl chloride pressure-equalizing dropping funnel,Then 50mL of toluene was added for dilution.Was heated to reflux with stirring was slowly added dropwise thionyl chloride diluent.During the reaction, the TLC method was used for tracking detection.After the reaction is completed, the reaction product is rotovaped under reduced pressure to remove the solvent,The product 4-chloro-3-ethyl-1-methyl-1H-pyrazole-5-carbonyl chloride,Used for the next reaction.
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃;
	With dichloro sulfoxide; N,N-dimethyl-formamide for 6h; Reflux;
	With dichloro sulfoxide for 5h; Reflux;	4-Chloro-3-ethyl-1-methyl-1H-pyrazole-5-carbonylchloride (5) A mixture of 4-chloro-3-ethyl-1-methyl-1H-pyrazole-5-carboxylic acid (4) (18.8 g, 0.1 mol) and SOCl2 (50 mL) was refluxed for 5 h. After the reaction was completed, the excess SOCl2 was removed. The residue 4-chloro-3-ethyl-1-methyl-1H-pyrazole-5-carbonyl chloride (5) was without further purification used directly for next step.
	With dichloro sulfoxide Reflux;	3.2.7. Methyl 3-(5-(4-Chloro-3-ethyl-1-methyl-1H-pyrazol-5-yl)-1,2,4-oxadiazol-3-yl)benzoate 12 The solution of intermediate 7 (0.94 g, 5.00 mmol) and thionyl chloride (10 mL)was added to a three-necked fask and refluxed. Afterwards, the solvent was removedto give 4-chloro-3-ethyl-1-methyl-1H-pyrazole-5-carbonyl chloride. Then, the mixture of intermediate 11 (0.97 g, 5.00 mmol), triethylamine (1.20 g, 12.00 mmol) and toluene (100 mL)was stirred at 0 °C for 2 h. The newly prepared 4-chloro-3-ethyl-1-methyl-1H-pyrazole-5-carbonyl chloride was added dropwise to react at 0 °C for 3 h, then heated to reflux for 2 h. The mixture was washed with water (150 mL) and a saturated sodium chloride solution, successively. Finally,the organic layer was dried with Na2SO4 and the solvent was removed to give 1.45 g product.
7.53 g	With sulfuryl dichloride In chloroform Reflux;	9 Example 9 Preparation of intermediate 12 represented by formula (12). In a 100 mL three-necked flask, 0.94 g (5.00 mmol) of intermediate 7 prepared by Example 5, 10 mL of thionyl chloride were added, and the reaction was heated to reflux. TLC monitoring of the raw material point basically disappeared, and the thionyl chloride was removed by rotary evaporation to obtain 4- Chloro-3-ethyl-1-methyl-1H-pyrazole-5-carbonyl chloride is for later use,Into a 250 mL three-necked flask, add 110.97 g (5.00 mmol) of the intermediate prepared in Example 8, 1.2 g (12.00 mmol) of triethylamine, 100 mL of anhydrous toluene, control the temperature to 0°C, stir and react for 2 h, then add dropwise The prepared 4-chloro-3-ethyl-1-methyl-1H-pyrazole-5-carbonyl chloride was continuously stirred for 3 hours at 0 °C, then heated to 113 °C for reflux reaction, and the progress of the reaction was monitored by TLC, and the reaction was completed in about 2 hours , the reaction solution was washed with 150 mL of distilled water, then washed with saturated aqueous sodium chloride solution, and the organic phase was dried by adding anhydrous sodium sulfate,Rotary evaporation, desolvation and drying were carried out to obtain 1.45 g of product with a yield of 83.8%.

Reference： [1]Current Patent Assignee: QINGDAO UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN105153037, 2017, B Location in patent: Paragraph 0017-0020
[2]Current Patent Assignee: QINGDAO UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN109320506, 2019, A Location in patent: Paragraph 0017; 0018; 0019; 0023
[3]Location in patent: experimental part Fang, Zhi-Yong; Jiang, Hong; Ye, Xiao-Dong [E-Journal of Chemistry, 2012, vol. 9, # 1, p. 211 - 218]
[4]Current Patent Assignee: WEIFANG SINO AGRI UNION CHEMICAL - CN110903279, 2020, A Location in patent: Paragraph 0299-0302
[5]Location in patent: scheme or table Zhang, Changjun; Dang, Yanqiu; Jiang, Lin; Wang, Liyin [Journal of Chemical Crystallography, 2009, vol. 39, # 11, p. 838 - 841]
[6]Location in patent: experimental part Song, Hongjian; Liu, Yuxiu; Xiong, Lixia; Li, Yongqiang; Yang, Na; Wang, Qingmin [Journal of Agricultural and Food Chemistry, 2012, vol. 60, # 6, p. 1470 - 1479]
[7]Location in patent: experimental part Yang, Tingting; Gao, Guohua [ARKIVOC, 2012, vol. 2012, # 6, p. 304 - 316]
[8]Location in patent: scheme or table Zhang, Da Qiang; Xu, Gao Fei; Fan, Zhi Jin; Wang, Dao Quan; Yang, Xin Ling; Yuan, De Kai [Chinese Chemical Letters, 2012, vol. 23, # 6, p. 669 - 672]
[9]Song, Hongjian; Liu, Yuxiu; Xiong, Lixia; Li, Yongqiang; Yang, Na; Wang, Qingmin [Journal of Agricultural and Food Chemistry, 2013, vol. 61, # 37, p. 8730 - 8736]
[10]Current Patent Assignee: ZHEJIANG BOSHIDA CROP SCIENCE AND TECH; ZHEJIANG BOSST CROP TECH - CN105777639, 2016, A Location in patent: Paragraph 0025; 0026; 0027
[11]Huang, Danling; Huang, Mingzhi; Liu, Aiping; Liu, Xingping; Liu, Weidong; Chen, Xiaoyang; Xue, Hansong; Sun, Jiong; Yin, Dulin; Wang, Xiaoguang [Journal of Heterocyclic Chemistry, 2017, vol. 54, # 2, p. 1121 - 1128]
[12]Current Patent Assignee: HUNAN HAILI CHEMICAL INDUSTRY COMPANY LIMITED - CN104788378, 2017, B Location in patent: Paragraph 0042; 0044; 0045
[13]Current Patent Assignee: YIFAN BIOTECHNOLOGY GROUP - CN104193681, 2017, B Location in patent: Paragraph 0033
[14]Huang, Danling; Huang, Mingzhi; Liu, Weidong; Liu, Aiping; Liu, Xingping; Chen, Xiaoyang; Pei, Hui; Sun, Jiong; Yin, Dulin; Wang, Xiaoguang [Chemical Papers, 2017, vol. 71, # 11, p. 2053 - 2061]
[15]He, Hai-Qin; Liu, Xing-Hai; Weng, Jian-Quan; Tan, Cheng-Xia [Letters in drug design and discovery, 2017, vol. 14, # 2, p. 195 - 200]
[16]Yan, Zhongzhong; Liu, Aiping; Huang, Mingzhi; Liu, Minhua; Pei, Hui; Huang, Lu; Yi, Haibo; Liu, Weidong; Hu, Aixi [European Journal of Medicinal Chemistry, 2018, vol. 149, p. 170 - 181]
[17]Current Patent Assignee: HUNAN CHEMICAL INDUSTRY INST - CN108117518, 2018, A Location in patent: Paragraph 0103; 0105
[18]Current Patent Assignee: HUNAN XINCHANGSHAN AGRICULTURAL DEV - CN109516956, 2019, A Location in patent: Paragraph 0044-0047
[19]Current Patent Assignee: QINGDAO UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN111187214, 2020, A Location in patent: Paragraph 0021; 0028-0030
[20]Balletti, Matteo; De Pedro Beato, Eduardo; Mazzarella, Daniele; Melchiorre, Paolo [Chemical Science, 2020, vol. 11, # 24, p. 6312 - 6324]
[21]Ning, Lei; Li, Hengzhao; Lai, Zemin; Szostak, Michal; Chen, Xingyue; Dong, Yanhong; Jin, Shuhui; An, Jie [Journal of Organic Chemistry, 2021, vol. 86, # 3, p. 2907 - 2916]
[22]Kang, Sheng-Jie; Zhao, Wen; Tan, Cheng-Xia; Weng, Jian-Quan; Peng, Wei-Li; Liu, Xing-Hai [Indian Journal of Heterocyclic Chemistry, 2021, vol. 31, # 1, p. 51 - 56]
[23]Tu, Min-Ting; Shao, Ying-Ying; Yang, Sen; Sun, Bin-Long; Wang, Ying-Ying; Tan, Cheng-Xia; Wang, Xue-Dong [Molecules, 2022, vol. 27, # 15]
[24]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - CN114920734, 2022, A Location in patent: Paragraph 0048-0049

6
[ 124800-34-6 ]
[ 127892-62-0 ]

Yield	Reaction Conditions	Operation in experiment
84%	Stage #1: ethyl 4-chloro-3-ethyl-1-methyl-1H-pyrazole-5-carboxylate With sodium hydroxide In ethanol for 3h; Reflux; Stage #2: With sulfuric acid
80%	With lithium hydroxide monohydrate; potassium hydroxide In ethanol	1.1 Dissolved with ethanol,Hydrolysis of 15% aqueous potassium hydroxide solution,The pH was then adjusted with hydrochloric acid until a solid precipitated.Filtering,Obtained solid compound G,Drying 3.69g,The yield was 80%.
	Stage #1: ethyl 4-chloro-3-ethyl-1-methyl-1H-pyrazole-5-carboxylate With lithium hydroxide monohydrate; sodium hydroxide In methanol for 4h; Reflux; Stage #2: In methanol Acidic conditions;

	With sodium hydroxide In lithium hydroxide monohydrate at 80℃; for 4h;
	With sodium hydroxide In lithium hydroxide monohydrate at 80℃; for 4h;	Synthesis of 1, 3-dimethyl-1H-pyrazole carboxylic acid (3a) and its analogues (3b-p) General procedure: 2a (0.05 mol) was added to a stirred mixture of NaOH (6.0 g, 0.15 mol) and water (100 mL). After 4 h under 80 °C, the mixture was poured into ice water and the pH was adjusted to acidic. Then 10 % HCl was slowly added to the solutions until a large amount of solids precipitated. After filtration, the solids were dried; 4.6 g (92 % purity) white solid (3a) was obtained. Yield 60 %; GC-MS (EI, 70Ev) (m/z 140 (M+). 3b-p were synthesized in a similar procedure.
	With sodium hydroxide In lithium hydroxide monohydrate at 80℃; for 4h;
	Stage #1: ethyl 4-chloro-3-ethyl-1-methyl-1H-pyrazole-5-carboxylate With sodium hydroxide Stage #2: With hydrogenchloride In lithium hydroxide monohydrate
	Stage #1: ethyl 4-chloro-3-ethyl-1-methyl-1H-pyrazole-5-carboxylate With sodium hydroxide In ethanol for 1h; Reflux; Stage #2: With hydrogenchloride	3.2.5. Intermediate 7 To a three-necked flask, we added compound 6 (2.10 g 0.01 mol) and ethanol (30 mL), then stirred it to dissolve it completely. Subsequently, NaOH (5 mL, 30%) was added to reflux for 1 h. The solvent was removed and then the pH was adjusted to 2-3 with HCl to precipitate a white solid. The crude product was recrystallized in ethanol and water to afford the pure product.
	With lithium hydroxide monohydrate; sodium hydroxide In ethanol for 1h; Reflux;	5 Example 5 Preparation of intermediate 7 represented by formula (7). 2.10 g (0.01 mol) of compound 6 prepared in Example 4 was added to a 100 mL three-necked flask, 30 mL of absolute ethanol was dissolved, 5 mL of 30% aqueous sodium hydroxide solution was added, and the reaction was refluxed. TLC tracked and monitored the reaction process. After about 1 h, the ethanol was removed by rotary evaporation, 20 mL of water was added, the pH of the system was adjusted to 2 with hydrochloric acid, and a white solid was precipitated, which was recrystallized with ethanol and water, which was intermediate 7.

Reference： [1]Location in patent: experimental part Song, Hongjian; Liu, Yuxiu; Xiong, Lixia; Li, Yongqiang; Yang, Na; Wang, Qingmin [Journal of Agricultural and Food Chemistry, 2012, vol. 60, # 6, p. 1470 - 1479]
[2]Current Patent Assignee: QINGDAO UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN109320506, 2019, A Location in patent: Paragraph 0017; 0018; 0019; 0022
[3]Location in patent: scheme or table Zhang, Da Qiang; Xu, Gao Fei; Fan, Zhi Jin; Wang, Dao Quan; Yang, Xin Ling; Yuan, De Kai [Chinese Chemical Letters, 2012, vol. 23, # 6, p. 669 - 672]
[4]Huang, Danling; Huang, Mingzhi; Liu, Aiping; Liu, Xingping; Liu, Weidong; Chen, Xiaoyang; Xue, Hansong; Sun, Jiong; Yin, Dulin; Wang, Xiaoguang [Journal of Heterocyclic Chemistry, 2017, vol. 54, # 2, p. 1121 - 1128]
[5]Huang, Danling; Huang, Mingzhi; Liu, Weidong; Liu, Aiping; Liu, Xingping; Chen, Xiaoyang; Pei, Hui; Sun, Jiong; Yin, Dulin; Wang, Xiaoguang [Chemical Papers, 2017, vol. 71, # 11, p. 2053 - 2061]
[6]Yan, Zhongzhong; Liu, Aiping; Huang, Mingzhi; Liu, Minhua; Pei, Hui; Huang, Lu; Yi, Haibo; Liu, Weidong; Hu, Aixi [European Journal of Medicinal Chemistry, 2018, vol. 149, p. 170 - 181]
[7]Kang, Sheng-Jie; Zhao, Wen; Tan, Cheng-Xia; Weng, Jian-Quan; Peng, Wei-Li; Liu, Xing-Hai [Indian Journal of Heterocyclic Chemistry, 2021, vol. 31, # 1, p. 51 - 56]
[8]Tu, Min-Ting; Shao, Ying-Ying; Yang, Sen; Sun, Bin-Long; Wang, Ying-Ying; Tan, Cheng-Xia; Wang, Xue-Dong [Molecules, 2022, vol. 27, # 15]
[9]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - CN114920734, 2022, A Location in patent: Paragraph 0040-0041

7
[ 128537-26-8 ]
[ 127892-62-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sulfuryl dichloride / toluene / 2 h / 100 °C 2.1: sodium hydroxide / ethanol / 3 h / Reflux 2.2: pH 2
	Multi-step reaction with 2 steps 1: dichloro sulfoxide / 1,2-dichloro-ethane / 2 h / 5 °C / Reflux 2: sodium hydroxide / lithium hydroxide monohydrate / 4 h / 80 °C
	Multi-step reaction with 2 steps 1: dichloro sulfoxide / ethyl acetate 2: lithium hydroxide monohydrate; potassium hydroxide / ethanol

	Multi-step reaction with 2 steps 1: dichloro sulfoxide 2: sodium hydroxide
	Multi-step reaction with 2 steps 1: sulfuryl dichloride / chloroform / 2 h / 40 - 60 °C 2: sodium hydroxide / ethanol / 1 h / Reflux
	Multi-step reaction with 2 steps 1: sulfuryl dichloride / chloroform / 2.5 h / 40 - 60 °C 2: lithium hydroxide monohydrate; sodium hydroxide / ethanol / 1 h / Reflux

Reference： [1]Song, Hongjian; Liu, Yuxiu; Xiong, Lixia; Li, Yongqiang; Yang, Na; Wang, Qingmin [Journal of Agricultural and Food Chemistry, 2012, vol. 60, # 6, p. 1470 - 1479]
[2]Huang, Danling; Huang, Mingzhi; Liu, Weidong; Liu, Aiping; Liu, Xingping; Chen, Xiaoyang; Pei, Hui; Sun, Jiong; Yin, Dulin; Wang, Xiaoguang [Chemical Papers, 2017, vol. 71, # 11, p. 2053 - 2061]
[3]Current Patent Assignee: QINGDAO UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN109320506, 2019, A
[4]Kang, Sheng-Jie; Zhao, Wen; Tan, Cheng-Xia; Weng, Jian-Quan; Peng, Wei-Li; Liu, Xing-Hai [Indian Journal of Heterocyclic Chemistry, 2021, vol. 31, # 1, p. 51 - 56]
[5]Tu, Min-Ting; Shao, Ying-Ying; Yang, Sen; Sun, Bin-Long; Wang, Ying-Ying; Tan, Cheng-Xia; Wang, Xue-Dong [Molecules, 2022, vol. 27, # 15]
[6]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - CN114920734, 2022, A

8
[ 13246-52-1 ]
[ 127892-62-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: hydrazine hydrate monohydrate; glacial acetic acid / 5 h / 80 °C 2.1: anhydrous sodium carbonate / dichloromethane / 5 h / 40 - 80 °C 3.1: sulfuryl dichloride / toluene / 2 h / 100 °C 4.1: sodium hydroxide / ethanol / 3 h / Reflux 4.2: pH 2
	Multi-step reaction with 3 steps 1: ethanol / 2 h / -5 °C 2: dichloro sulfoxide / 1,2-dichloro-ethane / 2 h / 5 °C / Reflux 3: sodium hydroxide / lithium hydroxide monohydrate / 4 h / 80 °C
	Multi-step reaction with 4 steps 1: hydrazine hydrate monohydrate / dichloromethane / 20 °C 2: dichloromethane / 80 °C 3: dichloro sulfoxide / ethyl acetate 4: lithium hydroxide monohydrate; potassium hydroxide / ethanol

	Multi-step reaction with 3 steps 1: 0 °C 2: dichloro sulfoxide 3: sodium hydroxide
	Multi-step reaction with 4 steps 1: hydrazine hydrate monohydrate / ethanol / 4 h / 0 °C 2: chloroform / 3 h / 35 - 50 °C 3: sulfuryl dichloride / chloroform / 2 h / 40 - 60 °C 4: sodium hydroxide / ethanol / 1 h / Reflux
	Multi-step reaction with 4 steps 1: hydrazine hydrate monohydrate / ethanol / 4 h / Cooling with ice 2: chloroform / 3.5 h / 35 - 50 °C 3: sulfuryl dichloride / chloroform / 2.5 h / 40 - 60 °C 4: lithium hydroxide monohydrate; sodium hydroxide / ethanol / 1 h / Reflux

Reference： [1]Song, Hongjian; Liu, Yuxiu; Xiong, Lixia; Li, Yongqiang; Yang, Na; Wang, Qingmin [Journal of Agricultural and Food Chemistry, 2012, vol. 60, # 6, p. 1470 - 1479]
[2]Huang, Danling; Huang, Mingzhi; Liu, Weidong; Liu, Aiping; Liu, Xingping; Chen, Xiaoyang; Pei, Hui; Sun, Jiong; Yin, Dulin; Wang, Xiaoguang [Chemical Papers, 2017, vol. 71, # 11, p. 2053 - 2061]
[3]Current Patent Assignee: QINGDAO UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN109320506, 2019, A
[4]Kang, Sheng-Jie; Zhao, Wen; Tan, Cheng-Xia; Weng, Jian-Quan; Peng, Wei-Li; Liu, Xing-Hai [Indian Journal of Heterocyclic Chemistry, 2021, vol. 31, # 1, p. 51 - 56]
[5]Tu, Min-Ting; Shao, Ying-Ying; Yang, Sen; Sun, Bin-Long; Wang, Ying-Ying; Tan, Cheng-Xia; Wang, Xue-Dong [Molecules, 2022, vol. 27, # 15]
[6]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - CN114920734, 2022, A

9
[ 26308-40-7 ]
[ 127892-62-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: anhydrous sodium carbonate / dichloromethane / 5 h / 40 - 80 °C 2.1: sulfuryl dichloride / toluene / 2 h / 100 °C 3.1: sodium hydroxide / ethanol / 3 h / Reflux 3.2: pH 2
	Multi-step reaction with 3 steps 1.1: sulfuryl dichloride / chloroform / 4 h / 0 °C / Reflux 2.1: potassium carbonate / propan-2-one / 10 h / 50 °C 3.1: lithium hydroxide monohydrate; sodium hydroxide / methanol / 4 h / Reflux 3.2: pH 2 / Acidic conditions
	Multi-step reaction with 3 steps 1: dichloromethane / 80 °C 2: dichloro sulfoxide / ethyl acetate 3: lithium hydroxide monohydrate; potassium hydroxide / ethanol

	Multi-step reaction with 3 steps 1: chloroform / 3 h / 35 - 50 °C 2: sulfuryl dichloride / chloroform / 2 h / 40 - 60 °C 3: sodium hydroxide / ethanol / 1 h / Reflux
	Multi-step reaction with 3 steps 1: chloroform / 3.5 h / 35 - 50 °C 2: sulfuryl dichloride / chloroform / 2.5 h / 40 - 60 °C 3: lithium hydroxide monohydrate; sodium hydroxide / ethanol / 1 h / Reflux

Reference： [1]Song, Hongjian; Liu, Yuxiu; Xiong, Lixia; Li, Yongqiang; Yang, Na; Wang, Qingmin [Journal of Agricultural and Food Chemistry, 2012, vol. 60, # 6, p. 1470 - 1479]
[2]Zhang, Da Qiang; Xu, Gao Fei; Fan, Zhi Jin; Wang, Dao Quan; Yang, Xin Ling; Yuan, De Kai [Chinese Chemical Letters, 2012, vol. 23, # 6, p. 669 - 672]
[3]Current Patent Assignee: QINGDAO UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN109320506, 2019, A
[4]Tu, Min-Ting; Shao, Ying-Ying; Yang, Sen; Sun, Bin-Long; Wang, Ying-Ying; Tan, Cheng-Xia; Wang, Xue-Dong [Molecules, 2022, vol. 27, # 15]
[5]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - CN114920734, 2022, A

10
[ 127892-62-0 ]
[ 1547032-01-8 ]

Yield	Reaction Conditions	Operation in experiment
83.1%	With silica gel; pyridinium chlorochromate In dichloromethane at 0 - 20℃;	7 1-methyl-3-ethyl-4-chloropyrazol-5-yl-formaldehyde according to the examples6 Preparation of 1-methyl-3-ethyl-4-chloropyridine5-yl-methanol.In a three-necked round bottom flask with a magnetic carrier1-methyl-3-ethyl-4-chloropyrazol-5-yl-methanol(3.48 g, 20 mmol),Dichloromethane (DCM, 50 mL),Silica gel (15g, 200-300 mesh),Cooled to 0-5 ° C,Slowly add PCC (6.45 g, 30 mmol).After joining,Natural warming to room temperature,Reaction overnight.After removal of the organic solvent, the column chromatography was 2.86 g of pure compound,Yield 83.1%

Reference： [1]Current Patent Assignee: HUNAN HAILI CHEMICAL INDUSTRY COMPANY LIMITED - CN104788378, 2017, B Location in patent: Paragraph 0075; 0076; 0077; 0078

11
[ 67-56-1 ]
[ 127892-62-0 ]
[ 128537-31-5 ]

Yield	Reaction Conditions	Operation in experiment
92%	In dimethyl sulfoxide for 8h; Reflux;	1.1 (1) synthesis of compound II To the 250 ml flask is added in three 18.85g (0.1 µM) 4 - chloro -3 - ethyl -1 - methyl - 1H - pyrazole -5 - carboxylic acid, 100 ml methanol, under the ice-bath adds by drops 17.85g (0.15 µM) thionyl chloride, stirring and heating to reflux, the stirring reaction 8h. Thin layer chromatography tracking response, the raw materials point disappears, stopping the reaction. The crude product is distilled under reduced pressure to remove the solvent to obtain 18.63g, yield 92%.

Reference： [1]Current Patent Assignee: QINGDAO UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN105037329, 2017, B Location in patent: Paragraph 0029; 0030; 0031; 0032

12
[ 127892-62-0 ]
[ 2688-84-8 ]
[ 2141416-47-7 ]

Yield	Reaction Conditions	Operation in experiment
64%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane for 3h;	1 Example 1Preparation method of diphenyl ether structure containing 5-pyrazole amide compound: 4-Chloro-3-ethyl-1-methyl-1H-pyrazole-5-carboxylic acid(1.50 g, 7.9 mmol), 2-phenoxyaniline (1.47 g, 7.9 mmol) were dissolved in 80 mL of dichloromethane,Et3N (1.60 g, 15.8 mmol) was added followed by EDCI (1.82 g, 9.5 mmol) and HOBt (1.29 g, 9.5 mmol). The reaction was complete for 3.0 h. The reaction was complete by TLC and diluted with dichloromethane (20 mL) 3 times, 50mL saturated brine to wash once,The aqueous layer was extracted with dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate, stripped of the solvent and the crude product was isolated by column chromatography.Obtained 1.8g reddish brown liquid, yield: 64%.

Reference： [1]Current Patent Assignee: Yang Zihui; Tian Hao; Xu Dan; Yi Shuai - CN107235905, 2017, A Location in patent: Paragraph 0029; 0030; 0031

13
[ 127892-62-0 ]
[ 89152-86-3 ]
[ 2097507-60-1 ]