89402-43-7|5-Chloro-2,3-difluoropyridine| Ambeed

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Structure of 5-Chloro-2,3-difluoropyridine
CAS No.: 89402-43-7

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Quality Control of [ 89402-43-7 ] Purity: 96% SDS Specification

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Product Details of [ 89402-43-7 ]

CAS No. :	89402-43-7
Formula :	C₅H₂ClF₂N
M.W :	149.53
SMILES Code :	C1=C(C=C(C(=N1)F)F)Cl
MDL No. :	MFCD04039314
InChI Key :	PERMDYZFNQIKBL-UHFFFAOYSA-N
Pubchem ID :	2783248

Safety of [ 89402-43-7 ]

GHS Pictogram:
Signal Word:	Danger
Hazard Statements:	H225-H302-H412
Precautionary Statements:	P273
Class:	3
UN#:	1993
Packing Group:	Ⅲ

Computational Chemistry of [ 89402-43-7 ] Show Less

Physicochemical Properties

Num. heavy atoms	9
Num. arom. heavy atoms	6
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	3.0
Num. H-bond donors	0.0
Molar Refractivity	29.16
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	12.89 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.68
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	2.01
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.85
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	1.95
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	2.91
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.28

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.53
Solubility	0.445 mg/ml ; 0.00297 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-1.91
Solubility	1.85 mg/ml ; 0.0124 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-3.18
Solubility	0.0988 mg/ml ; 0.000661 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.79 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	2.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	1.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.77

Application In Synthesis of [ 89402-43-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 89402-43-7 ]
Downstream synthetic route of [ 89402-43-7 ]

[ 89402-43-7 ] Synthesis Path-Upstream 1~1

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[ 514797-99-0 ]

References: [1] Chemistry - A European Journal, 2005, vol. 11, # 6, p. 1903 - 1910.
[2] European Journal of Organic Chemistry, 2002, # 24, p. 4174 - 4180.

[ 89402-43-7 ] Synthesis Path-Downstream 1~13

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[ 89402-43-7 ]
[ 207994-08-9 ]

References: [1]European Journal of Organic Chemistry,2002,p. 4174 - 4180.
[2]European Journal of Organic Chemistry,2002,p. 4174 - 4180.

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Yield	Reaction Conditions	Operation in experiment
85.94%	With ammonia; at 120℃; for 24h;Autoclave;	5-chloro-2,3-difluoro-pyridine (100g, 0.669mol) and ammonia (1.125L, 8.025mol) added to the autoclave.After the reaction 120 sealed 24h, the reaction was complete, the cooling pale yellow solid precipitation, filtration, the filter cake was washed with water, and the filtrate was extracted with ethyl acetate, and the combined organic layer was dried over anhydrous sodium sulfate, the organic phase was distilled off under reduced pressure, with beating a small amount of petroleum ether, filtration, and precipitation cake cake obtained will be collected at the same time to give the compound 2-amino-3-fluoro-5-chloropyridine 84.22g, yield 85.94%.
76%	With ammonia; In water; at 150℃; for 1h;Microwave irradiation;Product distribution / selectivity;	Example 4Preparation of 6-chloro-1-(pentan-3-yl)-1H-imidazo[4,5-b]pyridin-2-ol; Example 4(a) 5-chloro-3-fluoropyridin-2-amine: To a 20 mL microwave vial equipped with a stir bar was added 5-chloro-2,3-difluoropyridine (2.0 g, 41 mmol). Ammonium hydroxide (ca 12 mL) was then added and the mixture was stirred until homogeneous. The solution was capped and heated in the microwave reactor at 150 C. for three 20 minute increments until a white solid precipitated out of solution. The white solid was filtered, washed with water, and dried to afford 2-amino-5-chloro-3-fluoropyridine (1.5 g, 76% yield), characterized by 1H NMR (d6-DMSO).
73%	With ammonia; In water; at 165℃; for 3h;Product distribution / selectivity;	Example 5(a) 5-Chloro-3-fluoropyridin-2-amine.; To a stainless steel high pressure reactor was added 5-chloro-2,3-difluoropyridine (18.0 g) and ammonium hydroxide (65 mL). The reaction was heated to 165 C. for three hours. The reaction mixture was then cooled to room temperature and diluted with water (100 mL). The resultant solid was filtered, dried, re-dissolved in CH2Cl2, and passed through a silica gel plug to afford 12.8 g (73%) of the title compound as an off-white solid.

References: [1]Patent: CN105669539,2016,A .Location in patent: Paragraph 0058; 0059; 0060.
[2]Patent: US2008/242695,2008,A1 .Location in patent: Page/Page column 34.
[3]Patent: US2008/242695,2008,A1 .Location in patent: Page/Page column 34.

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Yield	Reaction Conditions	Operation in experiment
78%		Example 6(a) 5-Chloro-3-fluoro-2-hydroxypyridine. To a solution of NaOH (101 g, 2.5 mol) in water (500 mL) was added 5-chloro-2,3-difluoropyridine (101 g, 0.68 mol) as a liquid, and the resulting mixture was heated to reflux overnight. After cooling to room temperature, the mixture was filtered through a pad of celite and the pH was adjusted to 1 by the addition of concentrated HCl. The resulting solid was removed by filtration and dissolved in ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The title compound was obtained as a white solid (78 g, 78%) and was used without additional purification. The product was characterized by 1H NMR.
		First step A starting material (128) (35 g) and sodium hydroxide (20.6 g) were dissolved in water (300 mL), and the mixture was heated at reflux for 2.5 hours. After cooled to 0 C, concentrated hydrochloride acid (44.7 mL) was added, water (120 mL) was added, and the precipitated solid was collected by filtration to afford the crude product (129) (25.9 g). To the filtrate was added a 4 mol/L sodium hydroxide aqueous solution to make the solution neutral, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate to afford the crude product (2) (5.29 g).

References: [1]Patent: US2008/242695,2008,A1 .Location in patent: Page/Page column 36.
[2]Patent: EP2305672,2011,A1 .Location in patent: Page/Page column 88.

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[ 89402-43-7 ]
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[ 1227572-25-9 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of ethyl cyanoacetate (Aldrich) (4 g, 35.4 mmol) in anhydrous DMSO (30 mL) at 0 C. was added slowly NaH (60%, 1.42 g, 35.6 mmol). The mixture was stirred at 0 C. for 0.5 h, then 5-chloro-2,3-difluoropyridine (Combi-Blocks) (5.3 g, 35.6 mmol) was added. The reaction mixture was stirred at room temperature for 18 h. Water was added. The organic layer was separated, the aqueous layer was then extracted with ethyl acetate twice. The combined organic layers were washed with brine, dried over MgSO4, concentrated. The residue was purified by chromatography (EtOAc:hexanes=1:4, 1:1) to give (5-chloro-3-fluoro-pyridin-2-yl)-acetonitrile as a yellow gum (3.2 g, 37%).Step BTo the solution of (5-chloro-3-fluoro-pyridin-2-yl)-acetonitrile (2.8 g, 11.5 mmol) in DMSO (30 mL) was added NaCl (2 g, 34 mmol). The reaction mixture was heated at 170 C. for 2 h. The mixture was partitioned between ethyl acetate and water. Organic layer was separated, the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water, brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (EtOAc:hexanes=1:4, 1:3) to give (5-chloro-3-fluoro-pyridin-2-yl)-acetonitrile as a brown oil (0.85 g, 43%).

References: [1]Patent: US2011/118283,2011,A1 .Location in patent: Page/Page column 12.

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[ 94050-90-5 ]
[ 114420-56-3 ]

Yield	Reaction Conditions	Operation in experiment
97.1%		Adding water separately in the reaction kettle 20L, dimethyl sulfoxide 40L, sodium hydroxide to 9.5 kg (237mol), stirring, add R-2 - (P-hydroxy-phenoxy) propionic acid (optical purity 99.5%, content 99%) 18 kg (99mol), heating under stirring to the 45 C reaction 1 hour. By adding 17 kg (113.7mol) of 5-chloro -2,3-difluoro-pyridine, heating to 95 C reaction 6 hours, HPLC tracking of the reaction, when the raw material R-2 - (P-hydroxy-phenoxy) propionic acid is less than 1% of the, stop the reaction. Pressure reducing and recovering the solvent, adding residues 40L water to stir and dissolve, using 15% hydrochloric acid to adjust PH=3, separating solid under stirring, filtering, alkyne grass ester acid drying to 30 kg. Yield 97.1%, content of 99.1%, optical purity 99.2%.
91.3%		Add 15 mL of DMF to a 50 mL three-necked flask equipped with a constant pressure dropping funnel, a condenser and a thermometer.6.37g (0.035mol) R-HPPA, to be completely dissolved, add 7.26g (0.0525mol) K2CO3 particles, heat to 70-80 C stirMix for 2h, the system turns pink,4.76g (0.032mol) was then kept under constant temperature with a constant pressure dropping funnel.2,3-Difluoro-5-chloropyridine was slowly added dropwise to the reaction system, and it was dropped in about 30 minutes. Then, the temperature was raised to 90 C to keep the reaction, and the experiment was followed up by TLC, and the reaction was finished for about 8 hours. After the reaction solution is cooled to room temperature, adjust the pH of the system to 2-3 under ice bath conditions, and adjustDuring the process, a beige solid appeared and disappeared with the stirring. The ice bath was stirred for 1 hour, and there was a constant beige.The solid was precipitated, washed with water, suction filtered, dried to give 9.10 g of a beige solid, yield: 91.3%, and the purity was 97.5% by HPLC.
62%		N, N - dimethyl formamide (40 ml), (R)-2 - (4 - hydroxy-phenoxy) propionic acid (0.02 muM, 3 . 64g), potassium carbonate (0.02 muM, 2 . 76g), 75 C under stirring 0.5h after, then adding an equivalent amount of potassium carbonate, to continue stirring 0.5h. Slowly dropping 2,3-difluoro -5 - chloro pyridine (0.02 muM, 3 . 00g), after the completion of the dropping, the reaction temperature to maintain 75 C, 12h. Stop heating, cooling to room temperature, the reaction solution is poured into 100 ml ice water, dilute hydrochloric acid to adjust the pH 4 - 5, filter, a small amount of ice water washing three times, vacuum drying, be (R)-2-[4-(3-fluoro-5-chloro pyridine-2-yloxy) phenoxy] propionic acid white solid 3.86g, yield 62.0%.

62%		N, N-dimethylformamide (40 mL),(R) - (+) - 2- (4-hydroxyphenoxy) propionic acid (0.02 mol, 3.64 g)Potassium carbonate (0.02 mol, 2.76 g),After stirring at 75 C for 0.5 h,Then add the same amount of potassium carbonate,Continue stirring for 0.5 h.Slowly dropping 2,3-difluoro-5-chloropyridine (0.02 mol, 3.00 g)After dripping,The reaction temperature was maintained at 75 C,overnight.Stop heating,Cooled to room temperature,The reaction solution was poured into 200 mL of ice water,Dilute hydrochloric acid to adjust pH 4-5, filter,Washed with a small amount of ice water three times,Vacuum drying,(R) -2- [4- (3-fluoro-5-chloropyridin-2-oxy) phenoxy] propionic acid as a white solid, 3.86 g,Yield 62.0%.
62.0%		N, N-dimethylformamide (40 mL), (R) - (+) - 2- (4-hydroxyphenoxy) propionic acid (0.02 mol, 3.64 g) Potassium carbonate (0.02 mol, 2.76 g), After stirring at 75 C for 0.5 h, Then add the same amount of potassium carbonate, Continue stirring for 0.5 h. A solution of 2,3-difluoro-5-chloropyridine (0.02 mol, 3.00 g) After dripping, The reaction temperature was maintained at 75 C, overnight. Stop heating, Cooled to room temperature, The reaction solution was poured into 200 mL of ice water, Dilute hydrochloric acid to adjust pH 4-5, filter, Washed with a small amount of ice water three times, Vacuum drying, (R) -2- [4- (3-fluoro-5-chloropyridin-2-yloxy) phenoxy] propionic acid as a white solid, 3.86 g, Yield 62.0%.
62%		N, N-dimethylformamide (40 mL),(R) - (+) - 2- (4-hydroxyphenoxy) propionic acid(0.02 mol, 3.64 g),Potassium carbonate (0.02 mol, 2.76 g),Stirring at 0.5 C for 0.5 h, then add the same amount of potassium carbonate, continue stirring 0.5h.A solution of 2,3-difluoro-5-chloropyridine (0.02 mol, 3.00 g)After completion of the dropwise addition, the reaction temperature was maintained at 75 C overnight.The heating was stopped, the mixture was cooled to room temperature, and the reaction solution was poured into 200 mL of ice water,Dilute hydrochloric acid to adjust the pH 4-5, filter, washed with a small amount of ice water three times,Vacuum drying, too(R) -2- [4- (3-fluoro-5-chloropyridin-2-yloxy) phenoxy] propionic acidWhite solid 3.86 g,Yield 62.0%.
62%		N, N-dimethylformamide (40 mL),(R) - (+) - 2- (4-hydroxyphenoxy) propionic acid (0.02 mol, 3.64 g)Potassium carbonate (0.02 mol, 2.76 g),After stirring at 75 C for 0.5 h,Then add the same amount of potassium carbonate,Continue stirring for 0.5 h.A solution of 2,3-difluoro-5-chloropyridine (0.02 mol, 3.00 g)After dripping,The reaction temperature was maintained at 75 C,overnight.Stop heating,Cooled to room temperature,The reaction solution was poured into 200 mL of ice water,Dilute hydrochloric acid to adjust pH 4-5,filter,Washed with a small amount of ice water three times,Vacuum drying,(R) -2- [4- (3-fluoro-5-chloropyridin-2-yloxy) phenoxy] propionic acid as a white solid, 3.86 g,Yield 62.0%.
62%		N,N-dimethylformamide (40 mL),<strong>[94050-90-5](R)-(+)-2-(4-hydroxyphenoxy)propionic acid</strong> (0.02 mol, 3.64 g),Potassium carbonate (0.02 mol, 2.76 g),After stirring at 75 C for 0.5 h,Add the same amount of potassium carbonate,Stirring was continued for 0.5 h. Slowly add 2,3-difluoro-5-chloropyridine (0.02 mol, 3.00 g),After the completion of the dropwise addition, the reaction temperature was maintained at 75 C overnight. Stop heating and cool to room temperature. Pour the reaction solution into 200 mL of ice water.Dilute hydrochloric acid to adjust pH 4-5, filter,Wash three times with a small amount of ice water,Vacuum drying,(R)-2-[4-(3-Fluoro-5-chloropyridin-2-oxy)phenoxy]propionic acidWhite solid 3.86g,The yield was 62.0%.
62%		N, N - dimethyl formamide (40 ml), (R)-2 - (4 - hydroxy-phenoxy) propionic acid (0.02 muM, 3 . 64 g), potassium carbonate (0.02 muM, 2 . 76 g), 75 C under stirring 0.5 h after, then adding an equivalent amount of potassium carbonate, to continue stirring 0.5 h. Slowly dropping 2, 3 - difluoro -5 - chloro pyridine (0.02 muM, 3 . 00 g), after the completion of the dropping, the reaction temperature to maintain 75 C, 12 h. Stop heating, cooling to room temperature, the reaction solution is poured into 100 ml ice water, dilute hydrochloric acid to adjust the pH 4 - 5, filter, a small amount of ice water washing three times, vacuum drying, be (R)-2 - [4 - (3 - fluoro -5 - chloro pyridine -2 - yloxy) phenoxy] propionic acid white solid 3.86 g, yield 62.0%.
	With tetrabutylammomium bromide; potassium carbonate; In N,N-dimethyl-formamide; at 60 - 70℃; for 2h;	500 g of DMF was added to a 1000 mL four-necked flask, 100 g of compound A was charged,113.6 g of potassium carbonate and 5 g of tetrabutylammonium bromide, the temperature was raised to 60 C, and 120.31 g of the product was added dropwise2,3-difluoro-5-chloropyridine in 50 g of DMF in a mixed solution at a controlled temperature of 65 to 70 C,After completion of the dropwise addition, the reaction was allowed to proceed for about 2 hours, the reaction was completed,The pH was adjusted to 7 to 8 with hydrochloric acid, stirred for 1 hour, filtered, and the solid was the ether compound (Compound H) and dried.
5.92 g		(R) -2- (4- (5-chloro-3-fluoropyridin-2-yloxy)Phenoxy) propanoic acid In a reactor equipped with a magnetic stirrer,Thermometer and condenser 100mL three-necked flask was added N, N- dimethylformamide (DMF) (40mL),(R) 2- (4-hydroxyphenoxy) propionic acid (0.02 mol),After stirring to dissolve,Potassium carbonate (0.04 mol) was added portionwiseHeating to 60 ~ 80 stirring 0.5 ~ 1.0hr.2,3-Difluoro-5-chloropyridine (0.02 mol) was added dropwise,Continue stirring reaction 6 ~ 8hr.The reaction was cooled to room temperature,Poured into ice water (250 mL)To the mixture was slowly added dilute hydrochloric acid,Adjusted to pH = 4 ~ 5,filter,Washed,The title compound (5.92 g) was dried to give a white solid.
	With tetrabutylammomium bromide; potassium carbonate; In N,N-dimethyl-formamide; at 55 - 60℃; for 2h;	500 g of DMF was placed in a 1000 mL four-necked flask, and 100 g of Compound A, 113. 6 g of potassium carbonate and 5 g of tetrabutylammonium bromide were added, and the temperature was raised to 60 C. 90.3 g of Compound B was added dropwise, and the temperature was controlled at 60 to 55 C. At the end of the addition, the reaction was about 2 hours and the reaction was completed.Add to 1000g water,Adjust the pH to 7~8 with hydrochloric acid and stir for 1 hour.Filtered, the solid is etherified and dried.

References: [1]Patent: CN105418494,2016,A .Location in patent: Paragraph 0039; 0040; 0041; 0042; 0043.
[2]Patent: CN108752269,2018,A .Location in patent: Paragraph 0024; 0025.
[3]Patent: CN106632258,2017,A .Location in patent: Paragraph 0025; 0026.
[4]Patent: CN106699649,2017,A .Location in patent: Paragraph 0024; 0025; 0026.
[5]Patent: CN106632007,2017,A .Location in patent: Paragraph 0024; 0025; 0026.
[6]Patent: CN106699648,2017,A .Location in patent: Paragraph 0024; 0025; 0026.
[7]Patent: CN106632293,2017,A .Location in patent: Paragraph 0024; 0025; 0026.
[8]Patent: CN108218847,2018,A .Location in patent: Paragraph 0014-0016.
[9]Patent: CN108409654,2018,A .Location in patent: Paragraph 0014-0016.
[10]Chinese Chemical Letters,2011,vol. 22,p. 535 - 538.
[11]Patent: CN106632045,2017,A .Location in patent: Paragraph 0079; 0080.
[12]Patent: CN104277034,2017,B .Location in patent: Paragraph 0098; 0099.
[13]Patent: CN106632005,2019,B .Location in patent: Paragraph 0041; 0043; 0047; 0048.

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