[ CAS No. 76205-19-1 ] {[proInfo.proName]}

Name: 76205-19-1|1-(4-Chlorophenyl)-1H-pyrazol-3-ol|98%
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SKU: A173662
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Quality Control of [ 76205-19-1 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 76205-19-1 ]

SDS Specification

Alternatived Products of [ 76205-19-1 ]

Product Details of [ 76205-19-1 ]

CAS No. :	76205-19-1	MDL No. :	MFCD08459260
Formula :	C₉H₇ClN₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	DRENHOMDLNJDOG-UHFFFAOYSA-N
M.W :	194.62	Pubchem ID :	11356026
Synonyms :

Calculated chemistry of [ 76205-19-1 ] Expand+

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	11
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	50.6
TPSA :	38.05 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.71 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.09
Log Po/w (XLOGP3) :	2.5
Log Po/w (WLOGP) :	2.23
Log Po/w (MLOGP) :	2.1
Log Po/w (SILICOS-IT) :	1.65
Consensus Log Po/w :	2.11

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.18
Solubility :	0.128 mg/ml ; 0.000658 mol/l
Class :	Soluble
Log S (Ali) :	-2.94
Solubility :	0.221 mg/ml ; 0.00114 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.97
Solubility :	0.208 mg/ml ; 0.00107 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.64

Safety of [ 76205-19-1 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 76205-19-1 ]

* 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.

Downstream synthetic route of [ 76205-19-1 ]

[ 76205-19-1 ] Synthesis Path-Downstream 1~109

1
[ 76205-19-1 ]
[ 162225-07-2 ]
[ 235441-18-6 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; potassium tert-butylate; dimethyl sulfoxide; In cyclohexane; ethyl acetate; tert-butyl alcohol;	1a. Methyl [2-(1-(4-chlorophenyl)-3-pyrazolyloxy)pyridin-3-yl]glyoxylate At 60° C., 4.7 g (42 mmol) of potassium tert-butoxide were added a little at a time to a solution of 7.4 g (38.1 mmol) of <strong>[76205-19-1]1-(4-chlorophenyl)-3-hydroxypyrazole</strong> in 15 ml of tert-butanol. The mixture was stirred at this temperature for 1 hour and the solvent was then removed under reduced pressure. The residue was dissolved in 25 ml of abs. dimethyl sulfoxide, and a solution of 8.0 g (38.1 mmol) of methyl (2-chloropyridin-3-yl)glyoxylate in 10 ml of abs. dimethyl sulfoxide was then added at such a rate that the temperature did not exceed 30° C. After 30 minutes at room temperature, 50 ml of 0.5 N HCl were added and the reaction mixture was extracted repeatedly with ethyl acetate. The combined organic phases were washed with water and dried over sodium sulfate. The solvent was subsequently removed under reduced pressure. The resulting residue was purified by silica gel column chromatography using cyclohexane/ethyl acetate (10:1) as eluant. 5.5 g (40percent) of the title compound were obtained as a clear oil.

Reference： [1]Patent: US6362192,2002,B1

2
[ 76205-19-1 ]
[ 206198-90-5 ]
(ortho-[1-{4-chlorophenyl}-pyrazol-3-yl-oxymethyl]-phenyl)(5,6-dihydro-[1,4,2]dioxazin-3-yl)methanone O-methyl oxime [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N-methyl-acetamide; water;	Example 3 Synthesis of (ortho-[1-{4-chlorophenyl}-pyrazol-3-yl-oxymethyl]- phenyl)(5,6-dihydro-[1,4,2]dioxazin-3-yl)methanone O-methyl oxime A solution of 0.97 g of <strong>[76205-19-1]1-(para-chlorophenyl)-3-hydroxypyrazole</strong> in 20 ml of anhydrous dimethylformamide (DMF) was admixed with 0.13 g of sodium hydride and then stirred at 20-25 ° C. for approximately one hour. 1.34 g of the oxime from Example 2 were then added and the mixture was stirred at 60° C. for approximately three hours and then at 20-25° C. for approximately 14 hours. 300 ml of water were added and the mixture was then extracted with methyl tert-butyl ether (MTBE). The combined organic phases were washed with water and dried, and the solvent was then removed. The residue was chromatographed over silica gel (cyclohexane/ethyl acetate mixture [1:1]), giving 1.15 g of the title compound as a light-beige amorphous powder of m.p. 56-59° C. IR [cm-1]: 1546, 1502, 1480, 1464, 1358, 1093, 1054, 998, 935, 906.

Reference： [1]Patent: US6451790,2002,B1

3
[ 6119-12-6 ]
[ 71-48-7 ]
[ 76205-19-1 ]

Yield	Reaction Conditions	Operation in experiment
	In potassium hydroxide;	13. Preparation of 1-(4-chlorophenyl)-3-hydroxypyrazole using pure oxygen with Co(II) catalysis 900 g of a 6.9percent strength solution of 1-(4-chlorophenyl)-pyrazolidin-3-one in 5percent strength potassium hydroxide solution were admixed with 600 mg of cobalt(II) acetate and oxygen was passed into the solution at room temperature via a capillary in such a manner that it was just completely absorbed. After approximately 30 min, the reaction was complete according to HPLC monitoring, the temperature having increased to 40° C. 908 g of a solution were obtained which had a 1-(4-chlorophenyl)-3-hydroxypyrazole content of 6.7percent.

Reference： [1]Patent: US6040458,2000,A

4
[ 6119-12-6 ]
[ 76205-19-1 ]

Yield	Reaction Conditions	Operation in experiment
99.7%	With iron(III) chloride; acetic acid; at 50℃; for 4h;	First, 60 g of acetic acid was added to the apparatus,19.66 g (0.1 mol) of 1- (4-chlorophenyl) pyrazolidin-3-one was added with stirring,0.0162 g (0.0001 mol) of ferric chloride, and the temperature was raised to 50 C,4h after removing most of the solvent, add water, stirring, a large number of product precipitation,With sodium hydroxide solution to adjust the pH value to 7, continue stirring 0.5h,The yield was 99.7% and the content was 99.6% (LC), which was obtained by filtration to obtain 19.4 g of 1- (4-chlorophenyl) -3-pyrazolol.
91.2%	With dipotassium peroxodisulfate; sulfuric acid; In acetonitrile; for 6h;Reflux;	With a mechanical stir,Reflux condenser and a thermometer in a 250 ml four-necked reaction flask were charged with 19.6 g (0.1 mol)1- (4-chlorophenyl) pyrazolidin-3-one and 100 ml of acetonitrile,After stirring and dissolving,2 g (0.02 mol) of concentrated sulfuric acid and 32.4 g were added(0.12 mil) potassium persulfate,In 30-80 C (the optimum temperature of 75-80 C) heating reflux 6h,Most of the solvent B is distilled offNitrile,Cooled by adding 50 ml of water,With hydrochloric acid to adjust the pH to 1,Filtered and dried to obtain 17.7 g of product,Yield 91.2%.
84.2%	With hydrogenchloride; sodium nitrite; In water; for 3h;Inert atmosphere; Cooling with ice;	Under a nitrogen atmosphere, 0.80 g of 1-(4- chlorophenyl)pyrazolidin-3-one, 1.03 g of concentrated hydrochloric acid, and 3.0 g of water were mixed and ice-cooled. To this mixture, an aqueous solution prepared by dissolving 565.8 mg of sodium nitrite in 1.14 g of water was added dropwise. The obtained mixture was stirred with ice-cooling for 3 hours, water was added, and then the solid was collected by filtration. The obtained solid was washed with water and then hexane, followed by drying to give 0.80 g of 4-chlorophenyl-1H-pyrazol-3-ol (content: 83.3 wt %). Yield: 84.1%.

	With potassium hydroxide; potassium hexacyanoferrate(III); In water;	6. Preparation of 1-(4-chlorophenyl)-3-hydroxypyrazole using air with potassium hexacyanoferrate(III) catalysis 98.3 g of 1-(4-chlorophenyl)pyrazolidin-3-one were dissolved in a mixture of 641.3 g of water and 33.75 g of potassium hydroxide and 0.98 g of potassium hexacyanoferrate(III) were added. The mixture was heated to 80 C., passing in a vigorous air stream through a capillary, and was then further oxidized at this temperature. After cooling, the mixture was acidified to pH 2 with concentrated sulfuric acid. The solid separating off was filtered off with suction, washed with water and diisopropyl ether and dried. 76 g of a light-brown solid remained.
	With acetic acid; In water;	8. Preparation of 1-(4-chlorophenyl)-3-hydroxypyrazole using pure oxygen without catalysis under pressure The solution of 9.75 g of 1-(4-chlorophenyl)pyrazolidin-3-one in 150 g of water was charged into a 300 ml autoclave. Oxygen at 15 bar was then forced in; the mixture was heated to 50 C. and allowed to stand for six hours at this temperature. The mixture was cooled and adjusted to a pH of 5 by adding acetic acid. The solid which precipitated out was filtered off with suction, digested in water for 30 minutes at 60 C., and again filtered off with suction and dried. 9.4 g of the product remained as colorless powder having a content of 95.4%.
	In potassium hydroxide;	12. Preparation of 1-(4-chlorophenyl)-3-hydroxypyrazole using pure oxygen without catalysis 850 g of a 7.4% strength solution of 1-(4-chlorophenyl)-pyrazolidin-3-one in 5% strength potassium hydroxide solution were heated to 60 C. oxygen was introduced into the solution via a capillary in such a manner that it was just completely absorbed. After approximately 90 min, the reaction was complete according to monitoring by HPLC. 855 g of a solution were obtained which had a 1-(4-chlorophenyl)-3-hydroxypyrazole content of 7.3%.

Reference： [1]Patent: CN106008350,2016,A .Location in patent: Paragraph 0010; 0011
[2]Journal of Agricultural and Food Chemistry,2019
[3]Patent: CN104211641,2016,B .Location in patent: Paragraph 0052-0054
[4]Patent: US2017/8853,2017,A1 .Location in patent: Paragraph 0037; 0038; 0039; 0040; 0042; 0044; 0045
[5]Organic and Biomolecular Chemistry,2011,vol. 9,p. 1443 - 1453
[6]European Journal of Organic Chemistry,2011,p. 5323 - 5330
[7]Patent: US6040458,2000,A
[8]Patent: US6040458,2000,A
[9]Patent: US6040458,2000,A
[10]Bulletin of the Korean Chemical Society,2010,vol. 31,p. 3341 - 3347
[11]Journal of Chemical Research,2015,vol. 39,p. 594 - 600
[12]Heterocyclic Communications,2018,vol. 24,p. 165 - 169

5
[ 205178-82-1 ]
[ 922-67-8 ]
[ 76205-19-1 ]

Yield	Reaction Conditions	Operation in experiment
	In potassium tert-butylate; water; tert-butyl alcohol;	1.b 1-(4-Chlorophenyl)-3-hydroxypyrazole A solution of 57.5 g of 4-chlorophenylhydrazine hydrosulfate in 1,000 ml of tert-butanol was first treated in portions with 100.8 g of potassium tert-butoxide and then (after stirring for 10 min) in the course of 45 min at 45° C.-50° C. with a solution of 27.7 g of methyl propiolate in 90 ml of tertbutanol. After 1 h at boiling point, the mixture was allowed to cool and the solvent was removed under reduced pressure. The residue thus obtained was dissolved in 1,200 ml of water. The aqueous phase was first washed with methylene chloride and then acidified, the product being deposited as a solid. 47.6 g of the title compound were obtained, m.p.: 185°-187° C.

Reference： [1]Patent: US5707936,1998,A

6
[ 76205-19-1 ]
[ 1284183-66-9 ]

Reference： [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 1443 - 1453

7
[ 76205-19-1 ]
[ 1284183-67-0 ]

Reference： [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 1443 - 1453

8
[ 76205-19-1 ]
[ 1284183-69-2 ]

Reference： [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 1443 - 1453

9
[ 76205-19-1 ]
[ 1284183-62-5 ]
[ 1284183-64-7 ]

Reference： [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 1443 - 1453

10
[ 1073-70-7 ]
[ 76205-19-1 ]

Reference： [1]Organic and Biomolecular Chemistry,2011,vol. 9,p. 1443 - 1453
[2]European Journal of Organic Chemistry,2011,p. 5323 - 5330
[3]Bulletin of the Korean Chemical Society,2010,vol. 31,p. 3341 - 3347
[4]Journal of Chemical Research,2015,vol. 39,p. 594 - 600
[5]Journal of Agricultural and Food Chemistry,2019

11
[ 76205-19-1 ]
[ 1334322-60-9 ]
[ 175013-18-0 ]

Yield	Reaction Conditions	Operation in experiment
74%	With potassium carbonate; In N,N-dimethyl-formamide; at 50℃;	Example 12; /S/-{2-[/S/'-(4-chloro-phenyl)-pyrazol-3'-oxymethyl]-phenyl}-A/-methoxy-carbamic acid methyl ester; A/-Carbomethoxy-A/-methoxy-(2-chloromethyl)-aniline (0.20 g, 0.87 mmol), 1 -(4-chloro- phenyl)-3-hydroxypyrrazole (0.17 g, 0.87 mmol) and K2CO3 were suspended in DMF (10 ml). The reaction mixture was stirred at 50 °C overnight. Thin layer chromatography control showed complete consumption of both starting materials. The suspension was diluted with tert-butyl methyl ether (100 ml), extracted four times with water and dried over MgSC . The crude product could be optionally purified by column chromatography on S1O2 to give the desired product (0.25 g, 0.64 mmol, 74percent yield). Alternatively, the product could be purified by recrystallization from ethanol/hbO (3:1 (v/v)).
74%	With potassium carbonate; In N,N-dimethyl-formamide; at 50℃;	Example 12N-{2-[N'-(4-chloro-phenyl)-pyrazol-3'-oxymethyl]-phenyl}-N-methoxy-carbamic acid methyl esterN-Carbomethoxy-N-methoxy-(2-chloromethyl)-aniline (0.20 g, 0.87 mmol), 1-(4-chloro-phenyl)-3-hydroxypyrrazole (0.17 g, 0.87 mmol) and K2CO3 were suspended in DMF (10 ml). The reaction mixture was stirred at 50° C. overnight. Thin layer chromatography control showed complete consumption of both starting materials. The suspension was diluted with tert-butyl methyl ether (100 ml), extracted four times with water and dried over MgSO4. The crude product could be optionally purified by column chromatography on SiO2 to give the desired product (0.25 g, 0.64 mmol, 74percent yield). Alternatively, the product could be purified by recrystallization from ethanol/H2O (3:1 (v/v)).

Reference： [1]Patent: WO2011/113884,2011,A1 .Location in patent: Page/Page column 35
[2]Patent: US2013/5986,2013,A1 .Location in patent: Page/Page column 14

12
[ 76205-19-1 ]
[ 76205-20-4 ]

Yield	Reaction Conditions	Operation in experiment
85%	With thionyl chloride; N,N-dimethyl-formamide;Reflux;	General procedure: A mixture of SOCl2 (5 mL), Ia?Id (1.0 mmol), and a catalytic amount of DMF (0.1 mmol) wereheated under reflux for about 4 h (monitored by TLC), then excess SOCl2 was evaporated and H2O(200 mL) was added with good stirring. The precipitate that formed was filtered off, washed with H2O, andthen purified by a silica-gel column chromatography (petroleum ether/EtOAc = 5:1) to afford IIa?IId.

Reference： [1]European Journal of Organic Chemistry,2011,p. 5323 - 5330
[2]Molecules,2014,vol. 19,p. 8140 - 8150

13
[ 76205-19-1 ]
[ 1257339-28-8 ]
[ 1257338-98-9 ]

Reference： [1]Bulletin of the Korean Chemical Society,2010,vol. 31,p. 3341 - 3347

14
[ 106-47-8 ]
[ 76205-19-1 ]

Reference： [1]Bulletin of the Korean Chemical Society,2010,vol. 31,p. 3341 - 3347
[2]Journal of Chemical Research,2015,vol. 39,p. 594 - 600

15
[ 3240-94-6 ]
[ 76205-19-1 ]
[ 1392758-90-5 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 8211 - 8224,14

16
[ 1073-69-4 ]
[ 623-47-2 ]
[ 76205-19-1 ]

Reference： [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 8211 - 8224,14

17
[ 76205-19-1 ]
[ 78-95-5 ]
[ 1445342-06-2 ]

Yield	Reaction Conditions	Operation in experiment
		5.50 g (28.3 mmol) 1 -(4-chlorophenyl)pyrazol-3-ol, 3.91 g (28.3 mmol) potassium carbonate and 50 mg sodium iodide in 30 ml DMF have been stirred for 5 min at ambient temperature. Then 2.62 g (28.3 mmol) chloroacetone have been added dropwise while stirring which was continued at 60°C for 5 h. The mixture was poured into excess 10 percent aqueous lithium chloride solution and extracted with ethyl acetate three times. The combined extracts have been washed with 10 percent lithium chloride solution twice and dried with sodium sulfate. After removal of the solvent in vacuo the crude product has been purified by chromatography on silica. Yield 6.5 g. The product was used for the next step.
		Ex. 4a 1-[1-(4-Chlorophenyl)pyrazol-3-yl]oxypropan-2-one (11) 5.50 g (28.3 mmol) 1-(4-chlorophenyl)pyrazol-3-ol, 3.91 g (28.3 mmol) potassium carbonate and 50 mg sodium iodide in 30 ml DMF have been stirred for 5 min at ambient temperature. Then 2.62 g (28.3 mmol) chloroacetone have been added dropwise while stirring which was continued at 60° C. for 5 h. The mixture was poured into excess 10percent aqueous lithium chloride solution and extracted with ethyl acetate three times. The combined extracts have been washed with 10percent lithium chloride solution twice and dried with sodium sulfate. After removal of the solvent in vacuo the crude product has been purified by chromatography on silica. Yield 6.5 g. The product was used for the next step.

Reference： [1]Patent: WO2013/92224,2013,A1 .Location in patent: Page/Page column 62; 63
[2]Patent: US2014/323305,2014,A1 .Location in patent: Paragraph 0308

18
[ 76205-19-1 ]
cis-[3-methyloxiran-2-yl]methanol [ No CAS ]
(±)-1-(4-chlorophenyl)-3-[[(2R,3S)-3-methyloxiran-2-yl]methoxy]pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22.5 g		To 28.3 g (107.9 mmol) triphenylphosphine and 15. Og (127.7 mmol) cis-3- methyloxiran-2-yl]methanol (15) from the preceding experiment in 400 ml THF have been added with stirring at -75°C 22.9 g (1 13.0 mmol) azodicarbonic acid diisopropyl ester. The mixture has been stirred at this temperature for 5 min. Then 20.0 g (102.8 mmol) 1 -(4-chlorophenyl)-3-hydroxypyrazole have been added with stirring at - 70°C. The mixture was allowed to warm up to ambient temperature and stirred for about 1 d. After removal of the solvents in vacuo the crude product was stirred with 200 ml of diisopropylether from which 42 g of a solid substance have been collected and further purified by chromatography on 330 g silica with MTBE/heptane. Yield 22.5 g (82percent)
22.5 g		Ex. 5b Racemic 1-(4-chlorophenyl)-3-[[(2R,3S)-3-methyloxiran-2-yl]methoxy]pyrazole (16) To 28.3 g (107.9 mmol) triphenylphosphine and 15.0 g (127.7 mmol) cis-3-methyloxiran-2-yl]methanol (15) from the preceding experiment in 400 ml THF have been added with stirring at -75° C. 22.9 g (113.0 mmol) azodicarbonic acid diisopropyl ester. The mixture has been stirred at this temperature for 5 min. Then 20.0 g (102.8 mmol) <strong>[76205-19-1]1-(4-chlorophenyl)-3-hydroxypyrazole</strong> have been added with stirring at -70° C. The mixture was allowed to warm up to ambient temperature and stirred for about 1d. After removal of the solvents in vacuo the crude product was stirred with 200 ml of diisopropylether from which 42 g of a solid substance have been collected and further purified by chromatography on 330 g silica with MTBE/heptane. Yield 22.5 g (82percent).

Reference： [1]Patent: WO2013/92224,2013,A1 .Location in patent: Page/Page column 64; 65
[2]Patent: US2014/323305,2014,A1 .Location in patent: Paragraph 0314

19
[ 76205-19-1 ]
[ 850354-34-6 ]
[ 1445341-96-7 ]

Yield	Reaction Conditions	Operation in experiment
75%		To 8.09 g (30.8 mmol) triphenylphosphine in 200 ml THF have been added with stirring at -75°C 6.23 g (30.8 mmol) azodicarbonic acid diisopropyl ester. The mixture has been stirred at this temperature for 5 min. Then 10.39 g (28.8 mmol) (Z)-3-tributyl-stannanyl-but-2-en-1-ol have been added dropwise and stirred for 5 min at -75°C. After addition of 4.00 g (20.6 mmol) 1 -(4-chlorophenyl)-3-hydroxypyrazole at -75°C a red suspension was formed. The mixture was allowed to warm up to ambient temperature and stirred for 3 d. After removal of the solvents in vacuo 29 g oil have been collected and purified by chromatography on 120 g silica with MTBE/heptane. Yield 8.3 g (75percent) oil. delta = 0.85 (m); 0.95 (m); 1.30 (m); 1 .50 m); 2.00 (s); 4.65 (d); 5.90 (d); 6.43 (t); 7.35 (d); 7.52 (d); 7.68 (d).
75%		Ex. 1b 1-(4-Chloro-phenyl)-3-((Z)-3-tributylstannanyl-but-2-enyloxy)-1H-pyrazole (5) To 8.09 g (30.8 mmol) triphenylphosphine in 200 ml THF have been added with stirring at -75° C. 6.23 g (30.8 mmol) azodicarbonic acid diisopropyl ester. The mixture has been stirred at this temperature for 5 min. Then 10.39 g (28.8 mmol) (Z)-3-tributylstannanyl-but-2-en-1-ol have been added dropwise and stirred for 5 min at -75° C. After addition of 4.00 g (20.6 mmol) <strong>[76205-19-1]1-(4-chlorophenyl)-3-hydroxypyrazole</strong> at -75° C. a red suspension was formed. The mixture was allowed to warm up to ambient temperature and stirred for 3 d. After removal of the solvents in vacuo 29 g oil have been collected and purified by chromatography on 120 g silica with MTBE/heptane. Yield 8.3 g (75percent) oil. delta=0.85 (m); 0.95 (m); 1.30 (m); 1.50 m); 2.00 (s); 4.65 (d); 5.90 (d); 6.43 (t); 7.35 (d); 7.52 (d); 7.68 (d).

Reference： [1]Patent: WO2013/92224,2013,A1 .Location in patent: Page/Page column 61
[2]Patent: US2014/323305,2014,A1 .Location in patent: Paragraph 0299

20
[ 76205-19-1 ]
C₁₇H₁₈ClN₃O₄ [ No CAS ]

Reference： [1]Patent: WO2013/92224,2013,A1

21
[ 76205-19-1 ]
[ 1445333-46-9 ]

Reference： [1]Patent: WO2013/92224,2013,A1

22
[ 76205-19-1 ]
1-(2-(bromomethyl)-3-fluorophenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-fluorophenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1 .Location in patent: Page/Page column 784; 785

23
[ 76205-19-1 ]
1-(2-(bromomethyl)-3-chlorophenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-chlorophenyl)-4-methyl-1,4-dihydrotetrazole-5-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.61 g	With potassium carbonate; In acetonitrile; for 4h;Reflux;	A mixture of 1-(2-bromomethyl-3-chlorophenyl)-4-methyl-1,4-dihydrotetrazole-5-one (described in Reference Preparation example 3) 1.21 g, <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazole-3-ol</strong> 0.78 g, potassium carbonate 0.66 g and acetonitrile 30 mL was stirred with heating under reflux for four hours. To the reaction mixture after standing to cool was added water, and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-chlorophenyl)-4-methyl-1,4-dihydrotetrazole-5-one (hereinafter referred to as Present tetrazolinone compound 1) 0.61 g. _,;Present tetrazolinone Compound 1 1H-NMR (CDCl3) delta(ppm): 7.64 (1H, d, J=2.7 Hz), 7.62-7.60 (1H, m), 7.53-7.49 (2H, m), 7.45 (1H, t, J=8.0 Hz), 7.39-7.35 (3H, m), 5.80 (1H, d, J=2.7 Hz), 5.54 (2H, s), 3.61 (3H, s).
1.61 g	With potassium carbonate; In acetonitrile; for 4h;Reflux;	Preparation Example 1 A mixture of 1-(2-bromomethyl-3-chlorophenyl)-4-methyl-1,4-dihydrotetrazole-5-one (described in Reference Preparation example 3) 1.21 g, <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazole-3-ol</strong> 0.78 g, potassium carbonate 0.66 g and acetonitrile 30 mL was stirred with heating under reflux for four hours. To the reaction mixture after standing to cool was added water, and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-chlorophenyl)-4-methyl-1,4-dihydrotetrazole-5-one (hereinafter referred to as Present tetrazolinone compound 1) 0.61 g. Present Tetrazolinone Compound 1 1H-NMR (CDCl3) delta (ppm): 7.64 (1H, d, J=2.7 Hz), 7.62-7.60 (1H, m), 7.53-7.49 (2H, m), 7.45 (1H, t, J=8.0 Hz), 7.39-7.35 (3H, m), 5.80 (1H, d, J=2.7 Hz), 5.54 (2H, s), 3.61 (3H, s).
0.61 g	With potassium carbonate; In acetonitrile; for 4h;Reflux;	A mixture of 1-(2-bromomethyl-3-chlorophenyl)-4-methyl-1,4-dihydrotetrazole-5-one (described in Reference Preparation example 3) 1.21 g, <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazole-3-ol</strong> 0.78 g, potassium carbonate 0.66 g and acetonitrile 30 mL was stirred with heating under reflux for four hours. To the reaction mixture after standing to cool was added water, and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl)-3-chlorophenyl)-4-methyl-1,4-dihydrotetrazole-5-one (hereinafter referred to as Present tetrazolinone compound 1) 0.61 g.

0.61 g	With potassium carbonate; In acetonitrile; for 4h;Reflux;	Reference Synthesis Example 3 according 1- (2-bromomethyl-3-chlorophenyl) -4-methyl-1,4-dihydro-tetrazol-5-one 1.21 g, 1- (4- chlorophenyl) -1H pyrazol-3-ol 0.78 g, heated to reflux and potassium carbonate 0.66 g and acetonitrile 30 mL was stirred for 4 hours. By adding water to the reaction mixture bangraeng, followed by extracting with ethyl acetate. To the organic layer was washed with water and a saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. By applying the resulting residue to silica gel column chromatography to give 1- (2 - [1- (4-chlorophenyl) -1H- pyrazol-3-yl] oxy} methyl-3-chlorophenyl) -4 methyl-1,4-dihydro-tetrazol-5-one (hereinafter referred to as the present compound tetra BBIT 1) to obtain 0.61 g.
0.61 g	With potassium carbonate; In acetonitrile; for 4h;Reflux;	A mixture of 1-(2-bromomethyl-3-chlorophenyl)-4-methyl-1,4-dihydrotetrazole-5-one (described in Reference Preparation example 3) 1.21 g, <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazole-3-ol</strong> 0.78 g, potassium carbonate 0.66 g and acetonitrile 30 mL was stirred with heating under reflux for four hours. To the reaction mixture after standing to cool was added water, and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-chlorophenyl)-4-methyl-1,4-dihydrotetrazole-5-one (hereinafter referred to as Present tetrazolinone compound 1) 0.61 g.
0.61 g	With potassium carbonate; In acetonitrile; for 4h;Reflux;	A mixture of 1-(2-bromomethyl-3-chlorophenyl)-4-methyl-1,4-dihydrotetrazole-5-one (described in Reference Preparation example 3) 1.21 g, <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazole-3-ol</strong> 0.78 g, potassium carbonate 0.66 g and acetonitrile 30 mL was stirred with heating under reflux for four hours. To the reaction mixture after standing to cool was added water, and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-chlorophenyl)-4-methyl-1,4-dihydrotetrazole-5-one (hereinafter referred to as Present tetrazolinone compound 1) 0.61 g. (0193) Present Tetrazolinone Compound 1 (0194) 1H-NMR (CDCl3) delta(ppm): 7.64 (1H, d, J=2.7 Hz), 7.62-7.60 (1H, m), 7.53-7.49 (2H, m), 7.45 (1H, t, J=8.0 Hz), 7.39-7.35 (3H, m), 5.80 (1H, d, J=2.7 Hz), 5.54 (2H, s), 3.61 (3H, s).

Reference： [1]Patent: WO2013/162072,2013,A1 .Location in patent: Page/Page column 786; 787
[2]Patent: US2016/165890,2016,A1 .Location in patent: Paragraph 0220; 0221; 0222
[3]Patent: US2016/157488,2016,A1 .Location in patent: Paragraph 0192; 0193; 0194
[4]Patent: KR2016/33208,2016,A .Location in patent: Paragraph 0231 - 0235
[5]Patent: KR2016/33206,2016,A .Location in patent: Paragraph 0267-0275
[6]Patent: KR2016/33207,2016,A .Location in patent: Paragraph 0236-0240
[7]Patent: US2016/150788,2016,A1 .Location in patent: Paragraph 0192-0194

24
[ 76205-19-1 ]
1-(2-(bromomethyl)-3-bromophenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-bromophenyl)-4-methyl-1,4-dihydrotetrazole-5-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
24.6 g	With potassium carbonate; In acetonitrile; for 4h;Reflux;	A mixture of 1-(2-bromomethyl-3-bromophenyl)-4-methyl-1,4-dihydrotetrazole-5-one (described in Reference Preparation Example 6) 18.5 g, <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazole-3-ol</strong> 10.4 g, potassium carbonate 8.8 g and acetonitrile 400 mL was stirred with heating under reflux for four hours. To the reaction mixtures after standing to cool was added water and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-bromophenyl)-4-methyl-1,4-dihydrotetrazole-5-one (hereinafter referred to as Present tetrazolinone compound 2) 24.6 g.
24.6 g	With potassium carbonate; In acetonitrile; for 4h;Reflux;	Preparation Example 2 A mixture of 1-(2-bromomethyl-3-bromophenyl)-4-methyl-1,4-dihydrotetrazole-5-one (described in Reference Preparation Example 6) 18.5 g, <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazole-3-ol</strong> 10.4 g, potassium carbonate 8.8 g and acetonitrile 400 mL was stirred with heating under reflux for four hours. To the reaction mixtures after standing to cool was added water and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-bromophenyl)-4-methyl-1,4-dihydrotetrazole-5-one (hereinafter referred to as Present tetrazolinone compound 2) 24.6 g.
24.6 g	With potassium carbonate; In acetonitrile; for 4h;Reflux;	A mixture of 1-(2-bromomethyl-3-bromophenyl)-4-methyl-1,4-dihydrotetrazole-5-one (described in Reference Preparation Example 6) 18.5 g, <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazole-3-ol</strong> 10.4 g, potassium carbonate 8.8 g and acetonitrile 400 mL was stirred with heating under reflux for four hours. To the reaction mixtures after standing to cool was added water and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-[1-(4-chiorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-bromophenyl)-4-methy1-1,4-dihydrotetrazole-5-one (hereinafter referred to as Present tetrazolinone compound 2) 24.6 g.

24.6 g	With potassium carbonate; In acetonitrile; for 4h;Reflux;	Note described in Synthesis Example 6 1- (2-bromomethyl-3-bromo-phenyl) -4-methyl-1,4-dihydro-tetrazol-5-one 18.5 g, 1- (4- chlorophenyl) - 1H- pyrazol-3-ol 10.4 g, was stirred for 4 hours heating under reflux a mixture of potassium carbonate and 8.8 g of acetonitrile and 400 mL. By adding water to the reaction mixture bangraeng, followed by extracting with ethyl acetate.To the organic layer was washed with water and a saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. By applying the resulting residue to silica gel column chromatography to give 1- (2 - [1- (4-chlorophenyl) -1H- pyrazol-3-yl] oxy} methyl-3-bromophenyl) -4 -methyl-1,4-dihydro-tetrazol-5-one (hereinafter referred to as the tetra BBIT compound 2) was obtained 24.6 g.
24.6 g	With potassium carbonate; In acetonitrile; for 4h;Reflux;	A mixture of 1-(2-bromomethyl-3-bromophenyl)-4-methyl-1,4-dihydrotetrazole-5-one (described in Reference Preparation Example 6) 18.5 g, <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazole-3-ol</strong> 10.4 g, potassium carbonate 8.8 g and acetonitrile 400 mL was stirred with heating under reflux for four hours. To the reaction mixtures after standing to cool was added water and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-bromophenyl)-4-methyl-1,4-dihydrotetrazole-5-one (hereinafter referred to as Present tetrazolinone compound 2) 24.6 g.
24.6 g	With potassium carbonate; In acetonitrile; for 4h;Reflux;	A mixture of 1-(2-bromomethyl-3-bromophenyl)-4-methyl-1,4-dihydrotetrazole-5-one (described in Reference Preparation Example 6) 18.5 g, <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazole-3-ol</strong> 10.4 g, potassium carbonate 8.8 g and acetonitrile 400 mL was stirred with heating under reflux for four hours. To the reaction mixtures after standing to cool was added water and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-bromophenyl)-4-methyl-1,4-dihydrotetrazole-5-one thereinafter referred to as Present tetrazolinone compound 2) 24.6 g. (0196) Present Tetrazolinone Compound 2 (0197) 1H-NMR (CDCl3) delta(ppm): 7.81-7.79 (1H, m), 7.65 (1H, d, J=2.4 Hz), 7.54-7.50 (2H, m), 7.42-7.35 (4H, m), 5.81 (1H, d, J=2.4 Hz), 5.53 (2H, s), 3.60 (3H, s).

Reference： [1]Patent: WO2013/162072,2013,A1 .Location in patent: Page/Page column 791
[2]Patent: US2016/165890,2016,A1 .Location in patent: Paragraph 0223; 0224; 0225
[3]Patent: US2016/157488,2016,A1 .Location in patent: Paragraph 0195; 0196; 0197
[4]Patent: KR2016/33208,2016,A .Location in patent: Paragraph 0236 - 0240
[5]Patent: KR2016/33206,2016,A .Location in patent: Paragraph 0276-0283
[6]Patent: KR2016/33207,2016,A .Location in patent: Paragraph 0241-0245
[7]Patent: US2016/150788,2016,A1 .Location in patent: Paragraph 0195-0197

25
[ 76205-19-1 ]
1-(2-(bromomethyl)-3-iodophenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-iodophenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1 .Location in patent: Page/Page column 793; 794

26
[ 76205-19-1 ]
1-(2-(bromomethyl)-3-methoxyphenyl)-4-methyl-1,4-dihydro-5H-tetrazole-5-one [ No CAS ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-methoxyphenyl)-4-methyl-1,4-dihydrotetrazole-5-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.97 g	With potassium carbonate; In acetonitrile; for 4h;Reflux;	A mixture of 1-(2-bromomethyl-3-methoxyphenyl)-4-methyl-1,4-dihydrotetrazole-5-one (described in Reference Preparation Exmaple 9) 1.20 g, <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazole-3-ol</strong> 0.78 g, potassium carbonate 0.66 g, and acetonitrile 30 mL was stirred with heating under reflux for four hours. To the reaction mixtures after standing to cool was added water and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-methoxyphenyl)-4-methyl-1,4-dihydrotetrazole-5-one (hereinafter referred to as Present tetrazolinone compound 5) 0.97 g. Present tetrazolinone Compound 5 1H-NMR (CDCl3) delta(ppm): 7.63 (1H, d, J=2.7 Hz), 7.53-7.49 (2H, m), 7.46 (1H, dd, J=8.5, 8.0 Hz), 7.38-7.34 (2H, m), 7.08 (1H, d, J=8.5 Hz), 7.04 (1H, d, J=8.0 Hz), 5.80 (1H, d, J=2.7 Hz), 5.43 (2H, s), 3.92 (3H, s), 3.57 (3H, s).
0.97 g	With potassium carbonate; In acetonitrile; for 4h;Reflux;	Preparation Example 5 A mixture of 1-(2-bromomethyl-3-methoxyphenyl)-4-methyl-1,4-dihydrotetrazole-5-one (described in Reference Preparation Example 9) 1.20 g, <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazole-3-ol</strong> 0.78 g, potassium carbonate 0.66 g, and acetonitrile 30 mL was stirred with heating under reflux for four hours. To the reaction mixtures after standing to cool was added water and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-methoxyphenyl)-4-methyl-1,4-dihydrotetrazole-5-one (hereinafter referred to as Present tetrazolinone compound 5) 0.97 g. Present Tetrazolinone Compound 5 1H-NMR (CDCl3) delta (ppm): 7.63 (1H, d, J=2.7 Hz), 7.53-7.49 (2H, m), 7.46 (1H, dd, J=8.5, 8.0 Hz), 7.38-7.34 (2H, m), 7.08 (1H, d, J=8.5 Hz), 7.04 (1H, d, J=8.0 Hz), 5.80 (1H, d, J=2.7 Hz), 5.43 (2H, s), 3.92 (3H, s), 3.57 (3H, s)
0.97 g	With potassium carbonate; In acetonitrile; for 4h;Reflux;	A mixture of 1-(2-bromomethyl-3-methoxyphenyl)-4-methyl-1,4-dihydrotetrazole-5-one (described in Reference Preparation Exmaple 9) 1.20 g, <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazole-3-ol</strong> 0.78 g, potassium carbonate 0.66 g, and acetonitrile 30 mL was stirred with heating under reflux for four hours. To the reaction mixtures after standing to cool was added water and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-methoxyphenyl)-4-methyl-1,4-dihydrotetrazole-5-one (hereinafter referred to as Present tetrazolinone compound 5) 0.97 g.

0.97 g	With potassium carbonate; In acetonitrile; for 4h;Reflux;	Note described in Synthesis Example 9 1- (2-bromomethyl-3-methoxy-phenyl) -4-methyl-1,4-dihydro-tetrazol-5-one 1.20 g, 1- (4- chlorophenyl) - 1H- pyrazol-3-ol 0.78 g, was stirred for 4 hours heating under reflux a mixture of potassium carbonate and 0.66 g of acetonitrile and 30 mL.By adding water to the reaction mixture bangraeng, followed by extracting with ethyl acetate.To the organic layer was washed with water and a saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure.By applying the resulting residue to silica gel column chromatography to give 1- (2 - [1- (4-chlorophenyl) -1H- pyrazol-3-yl] oxy} methyl-3-methoxyphenyl) -4 -methyl-1,4-dihydro-tetrazol-5-one (hereinafter referred to as the tetra BBIT compound 5) was obtained 0.97 g.
0.97 g	With potassium carbonate; In acetonitrile; for 4h;Reflux;	A mixture of 1-(2-bromomethyl-3-methoxyphenyl)-4-methyl-1,4-dihydrotetrazole-5-one (described in Reference Preparation Example 9) 1.20 g, <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazole-3-ol</strong> 0.78 g, potassium carbonate 0.66 g, and acetonitrile 30 mL was stirred with heating under reflux for four hours. To the reaction mixtures after standing to cool was added water and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-methoxyphenyl)-4-methyl-1,4-dihydrotetrazole-5-one (hereinafter referred to as Present tetrazolinone compound 5) 0.97 g.
0.97 g	With potassium carbonate; In acetonitrile; for 4h;Reflux;	A mixture of 1-(2-bromomethyl-3-methoxyphenyl)-4-methyl-1,4-dihydrotetrazole-5-one (described in Reference Preparation Example 9) 1.20 g, i-(4-chlorophenyl)-1H-pyrazole-3-ol 0.78 g, potassium carbonate 0.66 g, and acetonitrile 30 mL was stirred with heating under reflux for four hours. To the reaction mixtures after standing to cool was added water and the mixtures were extracted with ethyl acetate. The organic layers were washed with water and saturated saline, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to a silica gel column chromatography to give 1-(2-{([1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-methoxyphenyl)-4-methyl-1,4-dihydrotetrazole-5-one (hereinafter referred to as Present tetrazolinone compound 5) 0.97 g. (0205) Present Tetrazolinone Compound 5 (0206) 1H-NMR (CDCl3) delta(ppm): 7.63 (1H, d, J=2.7 Hz), 7.53-7.49 (2H, m), 7.46 (1H, dd, J=8.5, 8.0 Hz), 7.38-7.34 (2H, m), 7.08 (1H, d, J=8.5 Hz), 7.04 (1H, d, J=8.0 Hz), 5.80 (1H, d, J=2.7 Hz), 5.43 (2H, s), 3.92 (3H, s), 3.57 (3H, s).

Reference： [1]Patent: WO2013/162072,2013,A1 .Location in patent: Page/Page column 811
[2]Patent: US2016/165890,2016,A1 .Location in patent: Paragraph 0232; 0233; 0234
[3]Patent: US2016/157488,2016,A1 .Location in patent: Paragraph 0204; 0205; 0206
[4]Patent: KR2016/33208,2016,A .Location in patent: Paragraph 0251 - 0255
[5]Patent: KR2016/33206,2016,A .Location in patent: Paragraph 0302-0310
[6]Patent: KR2016/33207,2016,A .Location in patent: Paragraph 0256-0260
[7]Patent: US2016/150788,2016,A1 .Location in patent: Paragraph 0204-0206

27
[ 76205-19-1 ]
1-(2-(bromomethyl)-3-(trifluoromethyl)phenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-(trifluoromethyl)phenyl)-4-methyl-1,4-dihydrotetrazol-5-thione [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1 .Location in patent: Page/Page column 817; 818

28
[ 76205-19-1 ]
1-(2-bromomethyl-3-nitrophenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-nitrophenyl)-4-methyl-1,4-dihydrotetrazol-5-thione [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1 .Location in patent: Page/Page column 815; 816

29
[ 76205-19-1 ]
1-(2-(bromomethyl)-3-(difluoromethyl)phenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-(difluoromethyl)phenyl)-4-methyl-1,4-dihydrotetrazol-5-thione [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1 .Location in patent: Page/Page column 816; 817

30
[ 76205-19-1 ]
1-(2-(bromomethyl)-3-ethoxyphenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-ethoxyphenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1 .Location in patent: Page/Page column 854

31
[ 76205-19-1 ]
1-(2-(bromomethyl)-3-(methylthio)phenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-(methylthio)phenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1 .Location in patent: Page/Page column 859; 860

32
[ 76205-19-1 ]
[ 77378-54-2 ]
3-[(2-nitro-6-methylphenyl)methoxy]-1-(4-chlorophenyl)pyrazole [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1 .Location in patent: Page/Page column 951; 952

33
[ 76205-19-1 ]
3-[(2-isocyanato-6-methylphenyl)methoxy]-1-(4-chlorophenyl)pyrazole [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1

34
[ 76205-19-1 ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-methyl)-4H-1,4-dihydrotetrazole [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1

35
[ 76205-19-1 ]
3-[(2-amino-6-methylphenyl)methoxy]-1-(4-chlorophenyl)pyrazole [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1

36
[ 76205-19-1 ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-cyanophenyl)-4-methyl-1,4-dihydrotetrazol-5-thione [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1

37
[ 76205-19-1 ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-ethylpenyl)-4-methyl-1,4-dihydroteterazole-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1
[2]Patent: US2016/157488,2016,A1
[3]Patent: KR2016/33207,2016,A
[4]Patent: US2016/150788,2016,A1

38
[ 76205-19-1 ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-cyclopropylphenyl)-4-methyl-1,4-dihydrotetrazole-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1
[2]Patent: US2016/157488,2016,A1
[3]Patent: KR2016/33208,2016,A
[4]Patent: KR2016/33206,2016,A
[5]Patent: US2016/150788,2016,A1

39
[ 76205-19-1 ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-(1-propenyl)phenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1

40
[ 76205-19-1 ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-propylphenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1

41
[ 76205-19-1 ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-(1-methylethyl)phenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1

42
[ 76205-19-1 ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-butylphenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1

43
[ 76205-19-1 ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-ethenylphenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1

44
[ 76205-19-1 ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-(2-propenyl)phenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1

45
[ 76205-19-1 ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-(1-methylethenyl)phenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1

46
[ 76205-19-1 ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-(trimethylsilanylethynyl)phenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1

47
[ 76205-19-1 ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-ethynylphenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1

48
[ 76205-19-1 ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-methylphenyl)-4-ethyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1

49
[ 76205-19-1 ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-methylphenyl)-4-(methoxymethyl)-1,4-dihydrotetrazol-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1

50
[ 76205-19-1 ]
1-(2-(bromomethyl)-3,6-dimethylphenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3,6-dimethylphenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1 .Location in patent: Page/Page column 862

51
[ 76205-19-1 ]
1-(2-(bromomethyl)-3-methyl-6-fluorophenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-methyl-6-fluorophenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1 .Location in patent: Page/Page column 875

52
[ 76205-19-1 ]
1-(2-(bromomethyl)-3-methyl-4-fluorophenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-methyl-4-fluorophenyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Reference： [1]Patent: WO2013/162072,2013,A1 .Location in patent: Page/Page column 873; 874

53
[ 922-67-8 ]
[ 1073-69-4 ]
[ 76205-19-1 ]

Reference： [1]Patent: WO2013/162072,2013,A1 .Location in patent: Page/Page column 954

54
[ 1073-69-4 ]
[ 140-88-5 ]
[ 76205-19-1 ]

Reference： [1]Molecules,2014,vol. 19,p. 8140 - 8150

55
[ 76205-19-1 ]
methyl (2E)-2-[2-([4-chloro-1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxy}methyl)phenyl]-2-(methoxyimino)acetate [ No CAS ]

Reference： [1]Molecules,2014,vol. 19,p. 8140 - 8150

56
[ 76205-19-1 ]
[ 133409-72-0 ]
(E)-methyl 2-(2-(((1-(4-chlorophenyl)-1H-pyrazol-3-yl)oxy)methyl)phenyl)-2-(methoxyimino)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%		General procedure: To a solution of Ib and IIa?IId (1.0 mmol) in acetone (30 mL) was added K2CO3 (1.5 mmol). Themixture was refluxed for 15 min and V (1.05 mmol) was added slowly. The mixture was refluxed forabout 4 h, then K2CO3 was filtered off. The solvent was evaporated under reduced pressure. Theresidue was purified by a silica-gel column chromatography (petroleum ether/EtOAc = 10:1) to affordproducts TMa?TMe.
82%	With potassium carbonate; In acetone; for 4h;Reflux;	K2CO3 (0.35 g, 2.5 mmol) was added to a solution of1-(4-chlorophenyl)-1H-pyrazol-3?ol (0.19 g, 1.0 mmol) in acetone(30 mL). Then methyl (E)-2-[2-(bromomethyl)phenyl]-2-(methoxyimino)acetate (0.3 g, 1.05 mmol) was added slowly. Themixture was refluxed for 4 h, filtered, and solvent was evaporatedunder reduced pressure. The residue was purified by flash columnchromatography (eluent: AcOEt/petroleum ether, 1 : 12 v/v) to affordpyrazole substrate 1i.
82%	With potassium carbonate; In acetone; for 5h;Reflux;	General procedure: Intermediates 1a?h (1.0 mmol) were dissolved in acetone (30 mL), and K2CO3 (2.5 mmol) and 4 (1.1 mmol) were added slowly. The reaction mixture was heated to reflux for 5h and cooled to room temperature. Then K2CO3 was filtered off and the solvent was evaporated under reduced pressure. The crude product was purified using a silica-gel column chromatography (petroleum ether/ ethyl acetate = 5:1) to afford products 5a?h.

Reference： [1]Molecules,2014,vol. 19,p. 8140 - 8150
[2]Journal of Chemical Research,2014,vol. 38,p. 658 - 661
[3]Journal of Chemical Research,2015,vol. 39,p. 594 - 600

57
[ 76205-19-1 ]
[ 133409-72-0 ]
(E)-2-(2-(((1-(4-chlorophenyl)-1H-pyrazol-3-yl)oxy)methyl)phenyl)-2-(methoxyimino)-N-methylacetamide [ No CAS ]

Reference： [1]Molecules,2014,vol. 19,p. 8140 - 8150
[2]Journal of Chemical Research,2015,vol. 39,p. 594 - 600

58
[ 76205-19-1 ]
methyl(Z,2E)-5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-4-methyl-pent-3-enoate [ No CAS ]
C₁₇H₁₈ClN₃O₄ [ No CAS ]

Reference： [1]Patent: US2014/323305,2014,A1

59
[ 76205-19-1 ]
[ 133409-72-0 ]
methyl (2E)-2-[2-([4-chloro-1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxy}methyl)phenyl]-2-(methoxyimino)acetate [ No CAS ]

Reference： [1]Helvetica Chimica Acta,2014,vol. 97,p. 1269 - 1282

60
[ 76205-19-1 ]
(Z,2E)-5-chloro-2-methoxyimino-N,3-dimethyl-pent-3-enamide [ No CAS ]
[ 1445331-27-0 ]

Yield	Reaction Conditions	Operation in experiment
51.9%	With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 23 - 60℃;	480 mg (2.4 mmol) (Z,2E)-5-chloro-2-methoxyimino-N,3-dimethyl-pent-3-enamide (see Ex. 6) and 500 mg (2.44 mmol) 1-(4-chlorophenyl)pyrazol-3-ol have been dissolved in 10 ml DMF. 680 mg (4.8 mmol) K2C03 and 20 mg KI have been added with stirring for 2 h at 60°C and then overnight at about 23 °C. The reaction mixture was diluted with water, extracted with MTBE, the combined extracts were washed with water once and dried over anhydrous Na2SO4. After re15 moval of the solvents in vacuo and the residue (0.71 g) chromatographed on silica gel usingcyclohexane-MTBE to afford a yellow oil that crystallized upon standing: 460 mg (51.9percent). mp: 126-128°C.

Reference： [1]Patent: WO2016/55404,2016,A1 .Location in patent: Page/Page column 17

61
[ 76205-19-1 ]
1-(1-tert-butyl-5-bromomethyl-1H-pyrazol-4-yl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]
1-(1-tert-butyl-5-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-1H-pyrazol-4-yl)-4-methyl-1,4-dihydro-tetrazol-5-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.06 g	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 3.5h;	1.10g of the C02A, 1.01g of <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazol-3-ol</strong> (referred to in Reference Production Example 12), 0.94g of potassium carbonate and 15mL of N, N- a mixture of dimethylformamide was stirred at 80 3.5 hours. Water was poured into the reaction mixture was cooled, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and a saturated saline solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The thus obtained residue was subjected to silica gel column chromatography to obtain 1.06g of 1-(1-tert-butyl-5-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-1H-pyrazol-4-yl)-4-methyl-1,4-dihydro-tetrazol-5-one (hereinafter referred to as present compound 1).

Reference： [1]Patent: CN105636955,2016,A .Location in patent: Paragraph 0555; 0556; 0557; 0558

62
[ 76205-19-1 ]
1-(2-bromomethylpyridin-3-yl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}pyridin-3-yl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.56 g	With potassium carbonate; In acetonitrile; for 4h;Reflux;	0.40g of the C05A, 0.29g of <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazol-3-ol</strong> (Preparation 12 mentioned in Reference Example), a mixture of potassium carbonate and 0.41g in 10mL acetonitrile It was heated under reflux for 4 hours with stirring. Water was poured into the reaction mixture was cooled, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and a saturated saline solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The thus obtained residue was subjected to silica gel column chromatography to obtain 0.56g of 1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}pyridin-3-yl)-4-methyl-1,4-dihydrotetrazol-5-one (hereinafter referred to as present compound 6).

Reference： [1]Patent: CN105636955,2016,A .Location in patent: Paragraph 0575; 0576; 0577; 0578

63
[ 76205-19-1 ]
1-(2-bromomethyl-3-thienyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]
1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-thienyl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.17 g	With potassium carbonate; In acetonitrile; for 2h;Reflux;	0.20g of the C07A, 0.14g of <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazol-3-ol</strong> (Preparation 12 mentioned in Reference Example), a mixture of potassium carbonate and 0.20g in 10mL acetonitrile It was heated under reflux for 2 hours with stirring. Water was poured into the reaction mixture was cooled, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and a saturated saline solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The thus obtained residue was subjected to silica gel column chromatography to obtain 0.17g of 1-(2-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-3-thienyl)-4-methyl-1,4-dihydrotetrazol-5-one (hereinafter referred to as the present compound 7).

Reference： [1]Patent: CN105636955,2016,A .Location in patent: Paragraph 0579; 0580; 0581; 0582

64
[ 76205-19-1 ]
1-(1-methyl-3-bromomethyl-1H-pyrazol-4-yl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]
1-(1-methyl-3-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-1H-pyrazol-4-yl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.21 g	With potassium carbonate; In acetonitrile; for 5h;Reflux;	0.25g of the C09A, 0.18g of <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazol-3-ol</strong> (Preparation 12 mentioned in Reference Example), a mixture of potassium carbonate and 0.15g in 10mL acetonitrile It was heated under reflux for 5 hours with stirring. Water was poured into the reaction mixture was cooled, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and a saturated saline solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The thus obtained residue was subjected to silica gel column chromatography to obtain 0.21g of 1-(1-methyl-3-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-1H-pyrazol-4-yl)-4-methyl-1,4-dihydrotetrazol-5-one (hereinafter referred to as present compound 10).

Reference： [1]Patent: CN105636955,2016,A .Location in patent: Paragraph 0591; 0592; 0593; 0594

65
[ 76205-19-1 ]
1-(1-methyl-5-bromomethyl-1H-pyrazol-4-yl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]
1-(1-methyl-5-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-1H-pyrazol-4-yl)-4-methyl-1,4-dihydrotetrazol-5-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.30 g	With potassium carbonate; In acetonitrile; for 5h;Reflux;	0.30g of the C12A, 0.21g of <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazol-3-ol</strong> (Preparation 12 mentioned in Reference Example), a mixture of potassium carbonate and 0.18g in 10mL acetonitrile It was heated under reflux for 5 hours with stirring. Water was poured into the reaction mixture was cooled, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and a saturated saline solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The thus obtained residue was subjected to silica gel column chromatography to obtain 0.30g of 1-(1-methyl-5-[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}-1H-pyrazol-4-yl)-4-methyl-1,4-dihydrotetrazol-5-one (hereinafter referred to as the present compound 11).

Reference： [1]Patent: CN105636955,2016,A .Location in patent: Paragraph 0595; 0596; 0597; 0598

66
[ 554-12-1 ]
[ 1073-69-4 ]
[ 76205-19-1 ]

Yield	Reaction Conditions	Operation in experiment
15.6 g		To 28.5g of 4-chlorophenyl hydrazine, 81.3g of 28percent sodium methoxide - methanol solution and 200mL of methanol, was added under ice-cooling 29.4g of methyl propionate, followed by stirring at 100 2 hours. To the reaction mixture was cooled, the mixture was added 100mL ice water and acidified with 30percent sulfuric acid, followed by stirring at 100 2 hours. Saturated saline solution was poured into the cooled reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and a saturated saline solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to give 15.6g of 1-(4-chlorophenyl)-1H-pyrazol-3-ol.

Reference： [1]Patent: CN105636955,2016,A .Location in patent: Paragraph 0671; 0672; 0673; 0674; 0675

67
[ 76205-19-1 ]
[ 612-23-7 ]
[ 220368-29-6 ]

Yield	Reaction Conditions	Operation in experiment
92.7%	With N-benzyl-N,N,N-triethylammonium chloride; sodium hydroxide; In water; acetone; at 40℃; for 3h;	Adding the container 1 - (4-chlorophenyl) - 3- the pyrazole is mellow, embodiment 5 of an organic solution of ortho-nitro benzyl chloride (organic solvent is acetone) and a phase transfer catalyst (benzyl triethyl ammonium chloride), to obtain the mixed solution; drop alkalizing under stirring, to the aqueous solution (sodium hydroxide), the reaction temperature is 40 °C, reaction time 3 hours; the reaction solution for sampling, sampling sample for detection HPLC, when the wherein the 1 - (4-chlorophenyl) - 3- the pyrazole is mellow amount is 1percent of the, stop reaction; pH of the solution is adjusted to the value 3, then by extraction, and recovering the solvent, purification after drying, obtain etheration product 2 - [(N-4-chlorophenyl) - 3- pyrazole oxygen radical methyl] nitrobenzene. In the above-mentioned process, an organic solution of ortho-nitro benzyl chloride concentration is 35percent, in the mixed solution, 1 - (4-chlorophenyl) - 3- the pyrazole is mellow, ortho-nitro benzyl chloride, alkali molar ratio of 1.0: 1.4 : 1.2; ortho-nitro benzyl chloride in organic solution with the phase transfer catalyst in the control of the mass ratio of 1 : 0.1. The embodiment can realize 2 - [(N-4-chlorophenyl) - 3- pyrazole oxygen radical methyl] nitrobenzene content 99.5percent, yield 92.7percent production effect.

Reference： [1]Patent: ,2016, .Location in patent: Paragraph 0063

68
[ 1073-70-7 ]
[ 140-88-5 ]
[ 76205-19-1 ]

Yield	Reaction Conditions	Operation in experiment
91.8%		The p-chlorophenylhydrazine hydrochloride prepared in Example 5 was transferred into a container, and 5 times the weight of the container was added to the container.Add toluene (2:1 sodium hydroxide solution and sodium carbonate), 15percent by weight of water to toluene, slowly stirring, and add the equivalent ratio of p-chlorophenylhydrazine hydrochloride. Heat to reflux and dehydrate until the water content is 160pm. heating;After cooling down to 70 ° C, based on the amount of p-chlorophenylhydrazine hydrochloride, 1.6 equivalent ratio of sodium alkoxide (sodium methoxide) was added to maintain the internal temperature at 65 ° C;In the amount of p-chlorophenylhydrazine hydrochloride, 1.8 equivalence ratio of acrylate (ethyl acrylate) was added dropwise. After 0.8 h was added dropwise, the temperature was refluxed for 1 h, and the low boiling material was distilled off until the internal temperature reached 85°C. Distillation, where the content of p-chlorophenylhydrazine was determined by HPLC at 0.4percent;The inner temperature was lowered to 60° C., 500 ml of water was added, and hydrochloric acid was added dropwise to adjust the pH to 2 and the organic phase was separated. After the aqueous phase was extracted with toluene, the organic phase was combined to obtain a toluene solution of the intermediate pyrazolone. The synthesis process involved in this embodiment includes the following sequence steps:The toluene solution prepared in Example 13 was transferred to another vessel, toluene was removed by distillation under reduced pressure, and a 1.8 equivalent ratio of alkali (2:1 KOH) was added based on the amount of p-chlorophenylhydrazine hydrochloride. Calcium hydroxide) and 8 times the weight of water, heated to 85 ° C;30percent hydrogen peroxide solution was slowly added dropwise with rapid stirring. The amount of hydrogen peroxide added was controlled to 1.1 equivalents based on the hydrochloride salt of p-chlorophenylhydrazine. After the addition was complete, the mixture was incubated for 2 hours. The reaction was stopped by HPLC when the pyrazolone content was 0.35percent.The reaction solution was allowed to come to room temperature, and the pH was adjusted to 2 by dropwise addition of hydrochloric acid, suction filtration, water washing, and drying under reduced pressure at 50°C to prepare 1-(4-chlorophenyl)-3-pyrazole alcohol with an HPLC content of 99.0. percent, yield 91.8percent.
79.2%		At room temperature, 36.16 g (99percent, 0.2 mol) of p-chlorophenylhydrazine hydrochloride was mixed with 216.96g of ethanol. Then 99.73 g (30percent, 0.44 mol) of 30 wtpercent ethanolic solution of sodium ethoxide and 24.49 g (98percent, 0.24 mol) of ethyl acrylate were added dropwise at 50 °C for 1 hour. After heating to 80 ° C, the reaction was stirred for 6 hours. After liquid-phase detection, the main raw material of p-chlorophenylhydrazine hydrochloride peak disappeared and the reaction is complete; followed by distillation under reduced pressure,Steamed to ethanol-free flow and then continue to steam 0.5h, then 145g of water was added to dissolve 5.46g (99percent, 0.02mol) of ferric chloride hexahydrate. Heating to 60 °C air (air flow rate of 70L / min) oxidation 12h to detect by liquid 1- (4-chlorophenyl) pyrazolidin-3-one peak disappears, the reaction is complete; add 50g water at 42°C , Hydrochloric acid was added dropwise to pH = 1, the temperature was lowered to 30°C , and 31.34 g of 1- (4-chlorophenyl) -3-pyrazolol was obtained by filtration with the yield of 79.2percent with 98.3percent content.

Reference： [1]Patent: CN105968048,2016,A .Location in patent: Paragraph 0072-0073; 0075-0076; 0084
[2]Patent: CN103588708,2016,B .Location in patent: Paragraph 0007; 0026; 0027

69
[ 1073-70-7 ]
[ 292638-85-8 ]
[ 76205-19-1 ]

Yield	Reaction Conditions	Operation in experiment
92%		In the p-chlorophenylhydrazine hydrochloride prepared in Example 4, 8 times by weight of toluene was added and the mixture was stirred with p-chlorobenzene.The equivalent ratio of hydrazine hydrochloride was added alkali (potassium bicarbonate), 10percent by weight of water, heated to reflux, dehydrated to a water content of 190 pm, and the heating was stopped;After the temperature was lowered, 1.05 equivalent ratio of sodium alkoxide (sodium methoxide) was added to maintain the internal temperature based on the amount of p-chlorophenylhydrazine hydrochloride.At 70°CBased on the amount of p-chlorophenylhydrazine hydrochloride, 1.5 equivalent ratio of acrylate (methyl acrylate) was added and the temperature was increased to refluxAfter distillation, distill off the low-boilers to an internal temperature of about 85 °C to stop distillation. At this time, the content of p-chlorophenylhydrazine was determined by HPLC at 0.30percent;Reduce the internal temperature to 65°C, adjust the pH to 2, separate the organic phase, extract the aqueous phase with toluene, and combine the organic phases to obtainIntermediate pyrazolone in toluene solution. The synthesis process involved in this embodiment includes the following sequence steps:After the toluene solution prepared in Example 12 was distilled under reduced pressure to remove toluene, the amount of p-chlorophenylhydrazine hydrochloride was added.Into the 1.8 equivalent ratio of alkali (2:1:1 sodium hydroxide, barium hydroxide, calcium hydroxide) and 10 times the weight of water, heated to 80 ° C;Add 30percent hydrogen peroxide solution with stirring. The amount of hydrogen peroxide solution is controlled at 1.6 when calculated as p-chlorophenylhydrazine hydrochloride.Amount, after adding, heat 1.5 hours;The reaction was stopped by HPLC when the pyrazolone content was 0.4percent;The reaction solution was cooled to room temperature, the pH was adjusted to 1.8, suction filtration, washing with water, and drying to give 1-(4-chlorophenyl)-3-Pyrazol, its HPLC content 99.2percent, yield 92.0percent.
76%		At room temperature, 36.16 g (99percent, 0.2 mol) of p-chlorophenylhydrazine hydrochloride was mixed with 198.88g of methanol. Then 90 g (30percent, 0.5 mol) of 30 wtpercent methanol solution of sodium methoxide and 35.1g (98percent, 0.4 mol) of methyl acrylate were added dropwise at 60 °C for 1 hour. After heating to 65° C, the reaction was stirred for 6 hours. After liquid-phase detection, the main raw material of p-chlorophenylhydrazine hydrochloride peak disappeared and the reaction is complete; followed by distillation under reduced pressure,Steamed to ethanol-free flow and then continue to steam 0.5h, then 145g of water was added to dissolve 5.46g (99percent, 0.02mol) of ferric chloride hexahydrate. Heating to 65 °C air (air flow rate of 70L / min) oxidation 11h to detect by liquid 1- (4-chlorophenyl) pyrazolidin-3-one peak disappears, the reaction is complete; add 50g water at 45°C , Hydrochloric acid was added dropwise to pH = 2,the temperature was lowered to 30°C , and 30.2 g of 1- (4-chlorophenyl) -3-pyrazolol was obtained by filtration with the yield of 76percent with 97.9percent content.

Reference： [1]Patent: CN105968048,2016,A .Location in patent: Paragraph 0071; 0074; 0077-0078; 0083
[2]Patent: CN103588708,2016,B .Location in patent: Paragraph 0007; 0036; 0037

70
[ 1073-70-7 ]
[ 79-06-1 ]
[ 76205-19-1 ]

Yield	Reaction Conditions	Operation in experiment
79.8%		At room temperature, 36.16 g (99percent, 0.2 mol) of p-chlorophenylhydrazine hydrochloride was mixed with 216.96g of ethanol. Then 31.6g (99percent, 0.46mol) of sodium ethoxide and 21.52 g (99percent, 0.3 mol) of acrylamide were added dropwise at 40 °C. After heating to 80 °C, the reaction was stirred for 6 hours. After liquid-phase detection, the main raw material of p-chlorophenylhydrazine hydrochloride peak disappeared and the reaction is complete; followed by distillation under reduced pressure,Steamed to ethanol-free flow and then continue to steam 0.5h, then 145g of water was added to dissolve 5.46g (99percent, 0.02mol) of ferric chloride hexahydrate. Heating to 80 °C air (air flow rate of 70L / min) oxidation 8h to detect by liquid 1- (4-chlorophenyl) pyrazolidin-3-one peak disappears, the reaction is complete; add 50g water at 50°C , Hydrochloric acid was added dropwise to pH = 1, the temperature was lowered to 30°C , and 31.39 g of 1-(4-chlorophenyl)-3-pyrazolol was obtained by filtration with the yield of 79.8percent with 98.9percent content.

Reference： [1]Patent: CN103588708,2016,B .Location in patent: Paragraph 0007; 0030; 0031

71
4-chlorophenylhydrazine hydrochloric acid salt [ No CAS ]
[ 76205-19-1 ]

Reference： [1]Patent: WO2016/113741,2016,A1

72
C₉H₉ClN₂O [ No CAS ]
[ 76205-19-1 ]

Yield	Reaction Conditions	Operation in experiment
83%	With copper(II) choride dihydrate; oxygen; In dimethyl sulfoxide; at 25 - 60℃; for 5h;	CuCl22H2O (2.5 mol percent relative to compound (II)) was added to the 1-(4-chlorophenyl)-pyrazolidin-3-one at 25-30°C. Air was moderately bubbled through the solution for 5 hours using deep-pipe. The oxidation reaction was maintained at 60°C. The flask was kept in an ice-bath in order to prevent exotherm. Once the conversion of 1-(4-chlorophenyl)-pyrazolidin-3-one to 1-(4-chlorophenyl)-3-hydroxy-1H-pyrazole of formula (III) was complete, the oxygen bubbling was stopped. Yield of 1-(4-chlorophenyl)-3 -hydroxy-1H-pyrazole: 83percent.

Reference： [1]Patent: WO2016/113741,2016,A1 .Location in patent: Page/Page column 18

73
[ 76205-19-1 ]
[ 3958-60-9 ]
[ 220368-29-6 ]

Yield	Reaction Conditions	Operation in experiment
96.5%	With tetrabutylammomium bromide; potassium hydroxide; In methanol; at 50℃; for 2h;Large scale;	(1) Condensation: 1 Add 1500 kg of methanol, 362 kg of potassium hydroxide and 10 kg of tetrabutylammonium bromide to the reaction vessel, start stirring, and increase the temperature to 50°C and then add 300 kg of 1-(4-chlorophenyl)-3- pyrazoleol, and 900kg of o-nitrobenzylbromide was added dropwise, and the reaction was carried out at 50°C for 2 hours, followed by cooling down to 15°C and centrifugation to obtain 450kg of the centrifuged solid as a crude condensate; 2). After adding 450kg of crude condensate to 500kg of methanol, wash it and cool it to 15°C filter, Filter cake at -0.08 Mpa, 60 °C drying 10 hours to give 360 kg condensation product, a purity of 98.5percent, a yield of 96.5percent;
70%	In dimethyl sulfoxide; at 25℃; for 1h;	Using the same flask as used in the preparation of 1-(4-chlorophenyl)-3- hydroxy-1H-pyrazole, a dropping funnel filled with 2-nitrobenzyl bromide of formula (IV) was connected. The ratio of 2-nitrobenzyl bromide to the <strong>[76205-19-1]1-(4-chlorophenyl)-3-hydroxy-1H-pyrazole</strong> present in the flask 1.7: 1 While being kept at a temperature of 25°C, the solution of 2-nitrobenzyl bromide was dropped into the flask at a rate of 0.5 ml/minute. After all of the 2-nitrobenzyl bromide was added to the flask, the reaction was mixed for 1 hour, until all of the <strong>[76205-19-1]1-(4-chlorophenyl)-3-hydroxy-1H-pyrazole</strong> was consumed. A small amount of NaOH 15percent was then added to the solution and the solution was then stirred for 30 minutes at 30°C. A small amount of H2O was added to the mixture in order to precipitate the crude product. The crude product was recrystallized using MCB. The product was dried in a vacuum oven at 25 mbar at 70°C. Yield of 1-(4-chlorophenyl)-3-[(2-nitrophenyl)methoxy]-1H-pyrazole: 70percent with a purity of 99.1percent.
	With sodium hydroxide; In water; at 48℃; for 1.6h;	First of all, to the condensation kettle containing o-nitrobenzyl bromobenzene solution into the solid1- (4-chlorophenyl) -3-pyrazole alcohol, wherein 1- (4-chlorophenyl) -3-pyrazole alcohol andNitrobenzyl bromide molar ratio of 1: 1.7; then heated to 48 ° C dropwise aqueous sodium hydroxide solution,The concentration of sodium hydroxide aqueous solution is 20percent; and then after the completion of the dropwise addition to cool to room temperature,And then incubated 1.6h crystallized, centrifuged; and then into the centrifuge after the solid was refined into refined kettle; and then into the above refining kettle methanol was heated to 49 ° C reflux 5 hours;Then then the aforementioned refining kettle material was cooled to room temperature, and then incubated 1.8h crystallization,Centrifuged; Finally, the centrifuged solid was dried to obtain pure product2 - [(N-4-chlorophenyl) -1H-pyrazol-3-yloxymethyl] nitrobenzene.Which before adding the catalyst and DMF in the condensation reactor before heating, pass into the oxygen,The temperature was raised to 50 dropping sodium hydroxide solution, the reaction time was 20h.

362 kg	With 1-bromo-butane; sodium hydroxide; at 80 - 82℃; for 2h;pH >= 13;Green chemistry; Large scale;	In the second step, in the 5m3 reactor, the initial raw material is 350 kg of p-chloroaniline, which is subjected to salt formation, diazotization, acidification, extraction, cyclization and oxidation.After the reaction of 1-(4-chlorophenyl)pyrazol-3-one to 1-(4-chlorophenyl)-3-pyrazolol,When 1-(4-chlorophenyl)pyrazol-3-one <2percent, liquid chromatography analysis at this time:P-chlorophenylhydrazine hydrochloride: 1.562percent;1-(4-chlorophenyl)pyrazol-3-one: 0.687percent;1-(4-Chlorophenyl)-3-pyrazolol: 95.832percent; high boiler (aldehyde): 1.919percent.All the o-nitrobenzyl bromide prepared in the above batch is put into the 1-(4-chlorophenyl)-3-pyrazolol solution, and an appropriate amount of sodium hydroxide solution is added to adjust the pH to 13 or more;Then, 0.2 kg of 4-butyl bromide catalyst with a purity of 99percent was added to the reaction vessel, and the temperature was raised to 80 ° C to 82 ° C, and the temperature was kept for 2 hours.Liquid chromatography analysis of 1-(4-chlorophenyl)-3-pyrazol <1percent was acceptable, stood still for 1 hour, layered, and cooled to 3 °C. In the third step, the lower layer was centrifuged and dried in a dryer to obtain 362 kg of 2-{(N-4-chlorophenyl)-3-pyrazoloxymethyl}nitrobenzene.Chromatographic purity:p-Chlorobenzoquinone hydrochloride: 0.315percent; 1-(4-chlorophenyl)pyrazol-3-one 0.112percent; o-nitrobenzyl bromide: 0.124percent,1-(4-Chlorophenyl)-3-pyrazol: 0.673percent; 2-{(N-4-chlorophenyl)-3-pyrazoloxymethyl}nitrobenzene:98.124percent. High boiler (aldehyde): 0.652percent.
	With potassium carbonate; In acetone; for 3h;Reflux;	1-(4-chlorophenyl)-3-pyrazol,Acetone and potassium carbonate are added to the reaction flask,After heating to reflux, a solution of o-nitrobenzyl bromide in acetone is added dropwise.After the completion of the dropwise addition, the reflux reaction is carried out for at least 3 hours.The acetone was concentrated and removed, and then methanol was refluxed for at least 20 min, cooled to room temperature, allowed to stand for at least 30 min, and filtered.Obtaining 2-[(N-p-chlorophenyl)-3-pyrazoloxymethyl]nitrobenzene for use;

Reference： [1]Patent: CN107935932,2018,A .Location in patent: Paragraph 0037; 0038; 0044; 0045; 0051; 0052
[2]Patent: WO2016/113741,2016,A1 .Location in patent: Page/Page column 17
[3]Patent: CN106883178,2017,A .Location in patent: Paragraph 0027; 0028; 0029; 0030; 0031; 0032; 0033-0043
[4]Patent: CN108218779,2018,A .Location in patent: Paragraph 0012; 0013
[5]Patent: CN109438354,2019,A .Location in patent: Paragraph 0019; 0045; 0066-0067

74
[ 151827-83-7 ]
[ 76205-19-1 ]
[ 175013-18-0 ]

Yield	Reaction Conditions	Operation in experiment
83%	With potassium carbonate; In N,N-dimethyl-formamide; acetone; for 7h;Reflux;	(5) Dissolving methyl N-methoxy-N- (2-bromomethylphenyl) carbamate with DMF as solvent0.12 mol of 1- (4-chlorophenyl) -pyrazolol, 0.15 mol of K2CO3 and acetone were placed in a reactor. After the temperature was raised to reflux, a solution of 0.1 mol of N-methoxy-N-2-bromomethylphenylcarbamate solution was refluxed for 7 hours. After filtration and drying, the solid material was completely dissolved by stirring with anhydrous methanol, and then cooled and crystallized to obtain a light The yellow solid is the target product pyraclostrobin. The purity of the product pyraclostrobin prepared by the above method was 89.1percent and the yield was 83percent

Reference： [1]Patent: CN106008347,2016,A .Location in patent: Paragraph 0027; 0033; 0034

75
[ 76205-19-1 ]
[ 88-73-3 ]
[ 220368-29-6 ]

Yield	Reaction Conditions	Operation in experiment
93%	With tetrabutylammomium bromide; sodium hydroxide; In 1,2-dichloro-ethane; chlorobenzene; at 50℃; for 4h;	A solution of 1- (4-chlorophenyl) -3-pyrazolol prepared in Example 22 in o-nitrochlorobenzyl prepared in Example 30 was added to a container (the organic solvent was a mass ratio 2: 1: 1 mixture of dichloroethane, chlorobenzene and acetone) and a phase transfer catalyst (tetrabutylammonium bromide) to obtain a mixed solution; dropping an aqueous solution of an alkali (sodium hydroxide) , The reaction temperature was 50 ° C and the reaction time was 4 hours. The reaction solution was sampled and the sample was detected by HPLC. When the amount of 1-(4-chlorophenyl) -3-pyrazolol was 0.5percent, the reaction was stopped 2 - [(N-4-chlorophenyl) -3-pyrazolyloxymethyl] nitrobenzene was obtained after adjusting the pH value of the solution to 3 and then extracting, recovering the solvent and purifying and drying.In the above process, the organic solution concentration of o-nitrochlorobenzyl chloride was 25percent, and the molar ratio of 1- (4-chlorophenyl) -3-pyrazolol, o-nitrochlorobenzyl chloride and base in the mixed solution was 1.0: 1.2: 1.2. The mass ratio of o-nitrochlorobenzyl chloride to the phase transfer catalyst in the organic solution was controlled at 1: 0.15.In this example, the production effect of 2-[(N-4-chlorophenyl)-3-pyrazolyloxymethyl]-1-nitrobenzene with 99.3percent content and 93.0percent yield was achieved

Reference： [1]Patent: CN106008348,2016,A .Location in patent: Paragraph 0137

76
4-chlorophenylhydrazine hydrochloric acid salt [ No CAS ]
[ 140-88-5 ]
[ 76205-19-1 ]

Yield	Reaction Conditions	Operation in experiment
91.8%		(2.1) The p-chlorophenylhydrazine hydrochloride obtained in Example 5 was transferred into a vessel, to which 5 times by weight of toluene was added, and the mixture was slowly added with a base such as p-chlorophenylhydrazine hydrochloride in an equivalent ratio (2: 1 solution of sodium hydroxide and sodium carbonate), 15percent by weight of water, heated to reflux, dehydration to water content of 160pm, stop heating; (2.2) After cooling to 70 ° C, 1.6 equivalents of sodium alkoxide (sodium methoxide) was added in an amount of p-chlorophenylhydrazine hydrochloride to maintain the internal temperature at 65 ° C;(2.3) to the amount of p-chlorophenyl hydrazine hydrochloride, dropping 1.8 equivalents of acrylate (ethyl acrylate), 0.8h drop is completed, the temperature reflux 1h, the distillation off the low boiling temperature to 85 about to stop the distillation, this time by HPLC detection of p-chlorophenyl hydrazine content of 0.4percent; (2.4) to the internal temperature to 60 ° C, add 500ml of water, dropping hydrochloric acid to adjust the pH value of 2, the separation of organic phase, the aqueous phase extracted with toluene, the organic phase, the intermediate pyrazolone toluene solution. (3.1) The toluene solution prepared in Example 13 was transferred to another vessel, toluene was removed by distillation under reduced pressure, and 1.8 equivalents of the base was added in an amount of p-chlorophenylhydrazine hydrochloride(2: 1 potassium hydroxide and calcium hydroxide) and 8 times the weight of water, heated to 85 ° C; (3.2) fast stirring slowly dropping 30percent hydrogen peroxide to chlorphenyl phenylhydrazine hydrochloride, the amount of hydrogen peroxide added to control the 1.1 equivalent, after the completion of the drop, the insulation 2 hours; (3.3) Stop the reaction when the pyrazolone content of 0.35percent was detected by HPLC;(3.4) The reaction solution was cooled to room temperature, hydrochloric acid was added dropwise to adjust the pH to 2, and the mixture was filtered, washed with water and dried at 50 ° C under reduced pressure to give 1- (4-chlorophenyl) -3-pyrazolol The HPLC content was 99.0percent and the yield was 91.8percent.

Reference： [1]Patent: CN106008348,2016,A .Location in patent: Paragraph 0091; 0100

77
[ 106-39-8 ]
[ 76205-19-1 ]

Reference： [1]Patent: CN106008348,2016,A
[2]Patent: CN106008348,2016,A

78
4-chlorophenylhydrazine hydrochloric acid salt [ No CAS ]
[ 292638-85-8 ]
[ 76205-19-1 ]

Yield	Reaction Conditions	Operation in experiment
92%		(2.1) 8-fold weight of toluene was added to the p-chlorophenylhydrazine hydrochloride obtained in Example 4, and a base (potassium hydrogencarbonate) was added in an equivalent amount of p-chlorophenylhydrazine hydrochloride under stirring,10percent by weight of water, heated to reflux, dehydrated to a water content of 190pm, stop heating; (2.2) after cooling to chlorobenzene hydrochloride terms of the amount of alcohol was added 1.05 equivalent ratio of sodium (sodium methylate), maintaining the internal temperature at 70 ; (2.3) To the amount of p-chlorophenylhydrazine hydrochloride, 1.5 equivalents of acrylic acid ester (methyl acrylate) was added, the temperature was refluxed, the low boiling substance was distilled off to an internal temperature of about 85 ° C, The content of p - chlorophenylhydrazine was 0.30percent by HPLC. (2.4). The pH was adjusted to 2 and the organic phase was separated. The aqueous phase was extracted with toluene and the organic phase was combined to obtain a toluene solution of the intermediate pyrazolone. Example 20(3.1) Toluene solution was (3.1) obtained in Example 12 was distilled under reduced pressure to remove toluene, chlorobenzene hydrochloride in terms of the amount. Added 1.8 equivalent ratio of alkali (2: 1: 1 sodium hydroxide, barium hydroxide, calcium hydroxide) and 10 times the weight of water, heated to 80 ; (3.2) with stirring was added 30percent hydrogen peroxide, p-chlorophenyl hydrazine hydrochloride to count, control the amount of hydrogen peroxide added in 1.6 equiv., After completion of the addition, 1.5 hours incubation; (3.3) Stop the reaction when the pyrazolone content of 0.4percent was detected by HPLC;(3.4) The reaction solution was cooled down to room temperature, adjusted to a pH of 1.8, filtered off, washed with water and dried to give 1- (4-chlorophenyl) -3-pyrazolol having an HPLC content of 99.2percent, yield of 92.0percent.

Reference： [1]Patent: CN106008348,2016,A .Location in patent: Paragraph 0090; 0099

79
[ 76205-19-1 ]
[ 3958-60-9 ]
1-(4-chlorophenyl)-3-[2-(nitrophenyl)methoxy]-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92.3%	With tetrabutylammomium bromide; potassium hydroxide; at 80 - 85℃; for 1.5h;	In a stirrer,thermometer,Reflux condenser and dropping funnel in a four-neck reaction flask,Add 19.5g (0.1piomicron1)3-hydroxy-ox- (p-chlorophenyl) pyrazole alcohol,5percent potassium hydroxide 134 g (0.12 mol) and 0.5 gTetrabutylammonium bromide, the reactants were heated to 80 ° C,At this temperature,Add o-nitrobenzyl bromide23.7 g (0.1 lmol),Dropping time is about 0.5h,Drop finished,Continue stirring at 80-85 ° C for 1.5 h.After cooling, the reaction is cooled to below 5 ° C,filter,The filter cake was washed with ethanol,Dried to give 30.4 g of a white solid,Yield 92.3percent.

Reference： [1]Patent: CN104211641,2016,B .Location in patent: Paragraph 0055-0057

80
[ 1073-69-4 ]
[ 76205-19-1 ]

Reference： [1]Patent: CN104211641,2016,B

81
[ 76205-19-1 ]
N-[3-([1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl)phenyl]hydroxylamine [ No CAS ]

Reference： [1]Patent: CN104211641,2016,B

82
[ 76205-19-1 ]
N-hydroxy-N-2-([N'-(p-chlorophenyl)pyrazole-3'-oxomethyl]phenyl)formic acid methyl ester [ No CAS ]

Reference： [1]Patent: CN104211641,2016,B

83
[ 76205-19-1 ]
C₁₉H₁₈ClN₃O₄ [ No CAS ]

Reference： [1]Patent: CN104211641,2016,B

84
[ 76205-19-1 ]
1-{2-(bromomethyl)-3-methylphenyl}-4-methyl-1,4-dihydro-5H-tetrazol-5-one [ No CAS ]
C₂₀H₁₈ClN₅O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88.3%	With potassium carbonate; In 5,5-dimethyl-1,3-cyclohexadiene; acetone; at 55℃; for 7h;Inert atmosphere;	Under a nitrogen atmosphere,124.4 g of potassium carbonate,And 254.9 g of acetone were mixed and heated to 55 ° C.,A solution of the compound (9) in xylene(A solution obtained by mixing 0.413 mol of the compound (9) and 135.3 g of xylene)And 0.470 mol of the compound (8)It was added simultaneously over 5 hours,And the mixture was stirred for 2 hours.Analysis of the obtained reaction mixture by high performance liquid chromatography revealed that the ratio of the compound (1) to the compound (10) was 31: 1,The combined yield of both compounds was 97.8percent. After addition of xylene to the reaction mixture, acetone was distilled off and washed with water at 80 ° C.further,After washing with aqueous sodium hydroxide solution and water,Water was removed from the organic layer by refluxing dehydration.The xylene solution of the obtained compound (1) (2.3 parts by weight based on 1 part by weight of the compound (1)Using amount part of xylene) was gradually cooled,After adding 255.3 g of n-heptane dropwise,By further gradual cooling,Crystals were precipitated.Under cooling,The resulting slurry was filtered,After washing with a mixed solvent of xylene and n-heptane,By drying,150.5 g of compound (1) was obtained.The yield calculated from the high performance liquid chromatography internal standard method was 88.3percent.

Reference： [1]Patent: JP2016/113426,2016,A .Location in patent: Paragraph 0031

85
[ 76205-19-1 ]
[ 478919-56-1 ]

Yield	Reaction Conditions	Operation in experiment
	With tetraphosphorus decasulfide; In 5,5-dimethyl-1,3-cyclohexadiene; at 150℃; for 24h;	A mixture of 3 g <strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazol-3-ol</strong> (produced in accordance with WO 2013/162072 A), 10.3 g of di-phosphorus pentasulfide, and 100 ml of xylene was stirred at 150° C. for 24 hours. The reaction mixture was concentrated under reduced pressure. The residue thus obtained was diluted with ethyl acetate and then filtered through silica gel. The filtrate was concentrated under reduced pressure to obtain 1.17 g of a crude product containing 1-(4-chlorophenyl)-1H-pyrazole-3-thiole.

Reference： [1]Patent: US2017/118983,2017,A1 .Location in patent: Paragraph 0138

86
[ 76205-19-1 ]
C₂₀H₁₅ClN₄O₃ [ No CAS ]

Reference： [1]Patent: CN107540664,2018,A
[2]Journal of Agricultural and Food Chemistry,2019

87
[ 1193-21-1 ]
[ 76205-19-1 ]
4-chloro-6-((1-(4-chlorophenyl)-1H-pyrazol-3-yl)-oxy)pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83.7%	With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 4h;	<strong>[76205-19-1]1-(4-chlorophenyl)-1H-pyrazol-3-ol</strong> (19.45 g, 0.1 mol) was used. Potassium carbonate (27.6 g, 0.2 mol), 250 mL of N,N-dimethylformamide added to the reaction flask, Stir at room temperature To the above solution was added 4,6-dichloropyrimidine (14.9 g, 0.1 mol). The reaction was heated to 100C for about 4 hours, and the solution gradually turned yellow during the reaction. After the completion of the TLC monitoring reaction, join Ethyl acetate and water were extracted, and the organic phase was dried over anhydrous magnesium sulfate, filtered, and dissolved under reduced pressure. Column chromatography of the residue gave a pale yellow solid (25.7 g, 0.084 mol), yield: 83.7%

Reference： [1]Journal of Agricultural and Food Chemistry,2019
[2]Patent: CN107540664,2018,A .Location in patent: Paragraph 0495-0498

88
[ 76205-19-1 ]
[ 220898-42-0 ]

Reference： [1]Patent: CN107935932,2018,A
[2]Patent: CN109438354,2019,A

89
[ 76205-19-1 ]
N-hydroxy-2-[(N-p-chlorophenyl)-3-pyrazolyloxymethyl]phenylcarbamic acid methyl ester [ No CAS ]

Reference： [1]Patent: CN107935932,2018,A
[2]Patent: CN109438354,2019,A

90
[ 76205-19-1 ]
[ 175013-18-0 ]

Reference： [1]Patent: CN107935932,2018,A
[2]Patent: CN109438354,2019,A

91
[ 76205-19-1 ]
[ 535-11-5 ]
ethyl 2-(1-(4-chlorophenyl)-3-pyrazolyloxy)propionate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 5h;	General procedure: The mixture of ethyl 2-bromopropanoate (11.00, 60.0 mmol), B/B? (9.93 g, 50.0 mmol) and potassium carbonate (5.60 g, 40.0 mmol) in N,N-dimethylformamide (DMF; 100 mL) was stirred at 100 C for about 5 h. After completion of the reaction (TLC), the reaction mixture was filtered. The filtrate was evaporated in vacuum to remove DMF and the residue was dissolved in ethyl acetate (50 mL). The organic phase was washed with water (20 mL), evaporated, and the crude product was further purified by recrystallization from ethanol to obtain D1: 12.06 g, yield 81.0%. White solid, m.p. 77-79 C. 1H NMR (300 MHz, CDCl3, 25 C, TMS): delta (ppm) 7.69 (d, J=3.0 Hz, 1H, pyrazol-5-H), 7.48 (d, J=8.7 Hz, 2H, 4-Cl-Ph-2,6-2H), 7.33 (d, J=8.7 Hz, 2H, 4-Cl-Ph-3,5-2H), 5.88 (d, J=2.7 Hz, 1H, pyrazol-4-H), 5.14 (q, J=6.9 Hz, 1H, CH), 4.23 (q, J=7.2 Hz, 2H, CH2), 1.63 (d, J=6.9 Hz, 3H, CH3), 1.26 (t, J=7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3, 25 C, TMS): delta (ppm) 172.1, 163.0, 138.4, 130.4, 129.2, 127.6, 118.5, 94.5, 72.9, 61.0, 17.9, 14.1; MS (ESI+) Calcd for C14H15ClN2O3 (M+H)+, m/z 295.08, found, 295.1; Anal. Calcd for C14H15ClN2O3: C, 57.05, H, 5.13, N, 9.50, found, C, 57.00, H, 5.12, N, 9.52%.
81%	With potassium carbonate; In N,N-dimethyl-formamide; at 90 - 100℃; for 5h;	1-(4-chlorophenyl)-3-pyrazol9.9g (60mmol),Ethyl 2-bromopropionate11.0 g (60 mmol),Potassium carbonate 5.6g (40mmol)And 100 ml of N,N-dimethylformamide was put into a 250 mL three-neck bottle.The temperature was raised to 90 to 100 C and maintained for 5 hours.Thin layer chromatography (TLC) followed the progress of the reaction (n-hexane / ethyl acetate = 4:1). After the conversion of 1-(4-chlorophenyl)-3-pyrazol was completed, the material was filtered to remove the salt, and the filter cake was washed with 20 ml of fresh N,N-dimethylformamide. The filtrate was combined, and the solvent was removed by evaporation under reduced pressure. The residue was washed with 50 g of ethyl acetate and 20 g of water, and the oil phase was distilled under reduced pressure to remove solvent. The residue was recrystallized from ethanol,A solid of 12.0 g was obtained in a yield of 81.0% (based on 1-(4-chlorophenyl)-3-pyrazol).
81%	With potassium carbonate; In N,N-dimethyl-formamide; at 90 - 100℃; for 5h;	9.93 g (50 mmol) of <strong>[76205-19-1]1-(4-chlorophenyl)-3-pyrazolyl-ol</strong>, 11.00 g (60 mmol) of ethyl 2-bromopropionate, 5.60 g (40 mol) of potassium carbonate, and100 ml of N,N-dimethylformamide was placed in a 250 mL three-necked flask, and the temperature was raised to 90 to 100 C for 5 hours. Thin layer chromatography (TLC) followed the progress of the reaction (n-hexane / ethyl acetate = 4:1). After the conversion of <strong>[76205-19-1]1-(4-chlorophenyl)-3-pyrazolyl-ol</strong> was completed, the material was filtered to remove the salt and the filter cake was washed with 20 ml of fresh N,N-dimethylformamide. The filtrate was combined, and the solvent was removed by evaporation under reduced pressure. The residue was dissolved in 50 mL of ethyl acetate, washed with water, an oil phase was distilled under reduced pressure. The residue was recrystallized from ethanol to give a white solid 12.06 g. Yield 81.0% (based on <strong>[76205-19-1]1-(4-chlorophenyl)-3-pyrazolyl-ol</strong>).

Reference： [1]Chinese Chemical Letters,2018,vol. 29,p. 915 - 918
[2]Patent: CN109867628,2019,A .Location in patent: Paragraph 0360-0362
[3]Patent: CN109867665,2019,A .Location in patent: Paragraph 0129-0131

92
[ 76205-19-1 ]
[ 105-36-2 ]
ethyl 2-((1-(4-chlorophenyl)-1H-pyrazol-3-yl)oxy)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84.6%	With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 5h;	General procedure: The mixture of ethyl 2-bromopropanoate (11.00, 60.0 mmol), B/B? (9.93 g, 50.0 mmol) and potassium carbonate (5.60 g, 40.0 mmol) in N,N-dimethylformamide (DMF; 100 mL) was stirred at 100° C for about 5 h. After completion of the reaction (TLC), the reaction mixture was filtered. The filtrate was evaporated in vacuum to remove DMF and the residue was dissolved in ethyl acetate (50 mL). The organic phase was washed with water (20 mL), evaporated, and the crude product was further purified by recrystallization from ethanol to obtain D1