[ CAS No. 2014-83-7 ] {[proInfo.proName]}

Name: 2014-83-7|2,6-Dichlorobenzyl Chloride|98%
Brand: Ambeed
SKU: A501530
Price: 9.0 USD
Availability: InStock
Rating: 93 (28 reviews)

,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

HazMat Fee +

There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

DV 2D 3D

3d Animation Molecule Structure of 2014-83-7

Structure of 2014-83-7 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 2014-83-7 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 2014-83-7 ]

SDS Specification

Alternatived Products of [ 2014-83-7 ]

Product Details of [ 2014-83-7 ]

CAS No. :	2014-83-7	MDL No. :	MFCD00000897
Formula :	C₇H₅Cl₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	LBOBESSDSGODDD-UHFFFAOYSA-N
M.W :	195.47	Pubchem ID :	74832
Synonyms :

Calculated chemistry of [ 2014-83-7 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	1
Num. H-bond acceptors :	0.0
Num. H-bond donors :	0.0
Molar Refractivity :	46.22
TPSA :	0.0 Å²

Pharmacokinetics

GI absorption :	Low
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.16 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.31
Log Po/w (XLOGP3) :	3.29
Log Po/w (WLOGP) :	3.58
Log Po/w (MLOGP) :	4.1
Log Po/w (SILICOS-IT) :	4.08
Consensus Log Po/w :	3.47

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-3.5
Solubility :	0.0614 mg/ml ; 0.000314 mol/l
Class :	Soluble
Log S (Ali) :	-2.97
Solubility :	0.212 mg/ml ; 0.00108 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.65
Solubility :	0.00434 mg/ml ; 0.0000222 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.37

Safety of [ 2014-83-7 ]

Signal Word:	Danger	Class:	8
Precautionary Statements:	P280-P305+P351+P338-P310	UN#:	3261
Hazard Statements:	H314	Packing Group:	Ⅱ
GHS Pictogram:

Application In Synthesis of [ 2014-83-7 ]

* 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 [ 2014-83-7 ]
Downstream synthetic route of [ 2014-83-7 ]

[ 2014-83-7 ] Synthesis Path-Upstream 1~4

1
[ 110-85-0 ]
[ 2014-83-7 ]
[ 102292-50-2 ]

Yield	Reaction Conditions	Operation in experiment
95.7%	for 4 h; Reflux	General procedure: Anhydrous piperazine (6.89 g, 80 mmol) was dissolved in 40 mL of freshly distilled THF. Once the piperazine was fully dissolved, 2.303 mL (20 mmol) of benzyl chloride was added dropwise. The reaction mixture was then refluxed for about 4 h until benzyl chloride disappeared, as assessed by TLC. The stirring mixture was allowed to cool, and then filtered. The filtrate was concentrated in a rotary evaporator and then diluted with EtOAc (100 mL) and water (50 mL), which was then made basic (pH>12) with a saturated 1 N NaOH aqueous solution and separated. The organic phase was washed with water (4 .x. 100 mL), brine (2 .x. 100 mL), dried over Na₂SO₄ and concentrated to yield an oil. Column chromatography (PE/EtOAc = 1:1 to EtOAc/MeOH = 5:1) afforded a pale yellow liquid.

Reference： [1] European Journal of Medicinal Chemistry, 2011, vol. 46, # 4, p. 1404 - 1414

2
[ 151-50-8 ]
[ 2014-83-7 ]
[ 3215-64-3 ]

Yield	Reaction Conditions	Operation in experiment
95%	With 18-crown-6 ether In ethanol; water for 1 - 3 h; Heating / reflux	EXAMPLE 13-(2,6-DichIoro-phenyl)-6-(2,4-difluoro-phenyIamino)-l-niethyl-pyrazolo[l,5-a]pyrimidin-2-one:Step l(2,6-DichIorophenyI)-acetonitrile: A 500 mL round-bottom flask was charged with a solution of KCN (26 g, 400.00 mmol) ,18-crown-6 (0.05 g) in water (60 ml). To this was added 1 ,3-dichloro-2- (chloromethyl)benzene (40 g, 206.24 mmol) in ethanol (300 ml). The resulting solution was allowed to stir for 1~3 hours while the temperature was maintained at reflux. The reaction progress was monitored by TLC (AcOEt: PE=I :4). The mixture was the concentrated to dryness on a rotary evaporator. The resulting residue was the transferred into a seperatory funnel, washed with water (5 x 100 mL) to afford 35.4 g (95percent) of 2-(2,6-dichlorophenyl)acetonitrile as a white solid. This product was used without further purification.

Reference： [1] Patent: WO2007/15866, 2007, A2, . Location in patent: Page/Page column 29; 31

3
[ 143-33-9 ]
[ 2014-83-7 ]
[ 3215-64-3 ]

Reference： [1] Chemische Berichte, 1975, vol. 108, p. 2448 - 2464
[2] Phytochemistry (Elsevier), 1988, vol. 27, # l, p. 51 - 72

4
[ 2014-83-7 ]
[ 6575-24-2 ]

Reference： [1] Phytochemistry (Elsevier), 1988, vol. 27, # l, p. 51 - 72
[2] Acta Chemica Scandinavica (1947-1973), 1955, vol. 9, p. 1012
[3] Chemische Berichte, 1975, vol. 108, p. 2448 - 2464

[ 2014-83-7 ] Synthesis Path-Downstream 1~88

1
[ 118-69-4 ]
[ 2014-83-7 ]

Yield	Reaction Conditions	Operation in experiment
90.3%	With copper(II) sulfide; In hexane; at 80 - 120℃; for 5h;Inert atmosphere;	The 161g2, 6 - dichloro toluene is added has been alkanes 87 g solvent after dissolving, adding copper sulfide catalyst 2.8 g, stirring, case of illumination, access chlorine, time 5 hours, to maintain the reaction temperature 80 - 120 C, reaction the exhaust gas through the water absorption, after the reaction, the reaction solution chloride washing, alkali cleaning, distillation to remove the solvent after cooling crystallization, filtering to obtain 174.5 g purity 99% of 2, 6 - [...], yield 90.3%, .
1347.04 g	With chlorine; at 80℃;UV-irradiation; Industrial scale;	Add 800 mL of raw material 2,6-dichlorotoluene to a 1000 mL self-circulating photoreactor.Using a 400W metal halide lamp with green light,The chlorine gas flow rate was 200 mL/min, and the chlorination reaction temperature in the early stage of the reaction was 80 C.When the content of 2,6-dichloromonobenzyl chloride reaches 70%,The chlorination reaction temperature was lowered to 50 C.After the reaction, 2,6-dichlorobenzylidene dichloride 1347.04 g was obtained.The content is 95.24%, 2,6-dichloromonobenzyl chloride 24.24g,The content was 1.71%, the impurity was 43.10 g, and the content was 3.05%.

Reference： [1]Patent: CN109721464,2019,A .Location in patent: Paragraph 0018-0023
[2]Journal of the American Chemical Society,1932,vol. 54,p. 647,656
[3]Journal of Organic Chemistry,1959,vol. 24,p. 536,543
[4]Patent: CN109776255,2019,A .Location in patent: Paragraph 0024-0033

2
[ 15258-73-8 ]
[ 2014-83-7 ]

Yield	Reaction Conditions	Operation in experiment
93%	With oxalyl dichloride; In dichloromethane; at 20℃;Reflux;	General procedure: To 16 (0.6 g, 0.6 mmol) was added dichloromethane (5 mL) in a round-bottom flask. After 10 min, oxalyl chlorideor oxalyl bromide was added (0.6 mmol). The reaction mixture was magnetically stirred at room temperature. Uponcessation of gas evolution, 4 was added (0.5 mmol), and the reaction mixture was heated to reflux. After thereaction was complete according to TLC analysis, the mixture was cooled to room temperature and filtered. Thesolid on the funnel was washed with dichloromethane (3 × 10 mL), and the filtrate was concentrated under reducedpressure to afford the desired product 5 in an essentially pure state based on 1H and 13C NMR spectroscopicanalyses.

Reference： [1]Beilstein Journal of Organic Chemistry,2014,vol. 10,p. 1397 - 1405
[2]Organic Letters,2018,vol. 20,p. 3061 - 3064
[3]Chemical and pharmaceutical bulletin,1967,vol. 15,p. 1990 - 1995

3
[ 143-33-9 ]
[ 2014-83-7 ]
[ 3215-64-3 ]

Reference： [1]Chemische Berichte,1975,vol. 108,p. 2448 - 2464
[2]Phytochemistry,1988,vol. 27,p. 51 - 72

4
[ 2014-83-7 ]
[ 35129-96-5 ]

Reference： [1]Angewandte Chemie - International Edition,2014,vol. 53,p. 10755 - 10758
Angew. Chem.,2014,vol. 126,p. 10931 - 10934,4
[2]ChemCatChem,2015,vol. 7,p. 226 - 227
[3]Advanced Synthesis and Catalysis,2012,vol. 354,p. 1914 - 1918
[4]Advanced Synthesis and Catalysis,2018,vol. 360,p. 1685 - 1692
[5]Acta Chemica Scandinavica (1947),1971,vol. 25,p. 3067 - 3071
[6]Organic Letters,2015,vol. 17,p. 1164 - 1167

5
[ 114-33-0 ]
[ 2014-83-7 ]
1-(2.6-Dichlorbenzyl)-3-(methylaminocarbonyl)-pyridiniumchlorid [ No CAS ]

Reference： [1]Zeitschrift fur Naturforschung, Teil B: Anorganische Chemie, Organische Chemie,1980,vol. 35,p. 1431 - 1434

6
[ 2014-83-7 ]
[ 17356-08-0 ]
[ 66279-46-7 ]

Yield	Reaction Conditions	Operation in experiment
94%	In ethanol; for 8h;Reflux;	a) Preparation of 2,6-dichlorobenzyl imidothiocarbamate hydrochloride <strong>[2014-83-7]2,6-Dichlorobenzyl chloride</strong> (19.0 g, 97 mmol) is initially charged in 200 ml of ethanol. Thiourea is added, and the mixture is stirred at reflux for 8 hours. The reaction is concentrated and the solid is triturated with tetrahydrofuran, filtered off with suction and dried. This gives 26.12 g of product (94% of theory). The salt is reacted further without any further reaction steps.

Reference： [1]Patent: US2010/255988,2010,A1 .Location in patent: Page/Page column 23
[2]Il Farmaco,1990,vol. 45,p. 617 - 630

7
[ 2014-83-7 ]
[ 87-42-3 ]
[ 70091-24-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 24h;	General procedure: 6-Chloro-9H-purine (2 g, 12.9 mmol), K2CO3 (2.2 g,14.2 mmol), and the appropriate alkyl bromide or benzyl chloride derivative (14.2 mmol) were combined in DMF (25 mL) in a 100-mL round-bottomed flask, and the resulting mixture was stirred for 24 h at room temperature. After the reaction was completed (TLC), the mixture was poured into water (50 mL), and then extracted with CH2Cl2. The combined organic extracts were washed with water, dried (MgSO4), and concentrated to dryness in vacuo. The residue was purified by chromatography on silica gel, eluting with CH2Cl2, to give compounds 1a-1q as white solids.

Reference： [1]Journal of Organic Chemistry USSR (English Translation),1989,vol. 25,p. 1611 - 1615
Zhurnal Organicheskoi Khimii,1989,vol. 25,p. 1783 - 1788
[2]Medicinal Chemistry Research,2014,vol. 23,p. 4619 - 4626

8
[ 2014-83-7 ]
[ 443-72-1 ]
[ 70091-25-7 ]

Yield	Reaction Conditions	Operation in experiment
62%	With potassium carbonate; In N,N-dimethyl acetamide;	EXAMPLE 10 In a procedure analogous to that of Example 9, by using 1.49 g of <strong>[443-72-1]6-methylaminopurine</strong>, 1.38 g of potassium carbonate, 50 ml of N,N-dimethylacetamide and 3.92 g of 2,6-dichlorobenzyl chloride, there was obtained 1.9 g of 9-(2,6-dichlorobenzyl)-<strong>[443-72-1]6-methylaminopurine</strong> as colorless needles (yield: 62%), m.p. 219-220 C. NMR spectrum of this product is identical with that of the corresponding compound synthesised in Example 2.

Reference： [1]Journal of Organic Chemistry USSR (English Translation),1989,vol. 25,p. 1611 - 1615
Zhurnal Organicheskoi Khimii,1989,vol. 25,p. 1783 - 1788
[2]Patent: US4189485,1980,A

9
[ 2014-83-7 ]
[ 443-72-1 ]
[ 125486-32-0 ]
[ 125486-34-2 ]

Reference： [1]Journal of Organic Chemistry USSR (English Translation),1989,vol. 25,p. 1611 - 1615
Zhurnal Organicheskoi Khimii,1989,vol. 25,p. 1783 - 1788

10
[ 2014-83-7 ]
[ 938-55-6 ]
[ 70091-22-4 ]
[ 125486-36-4 ]

Reference： [1]Journal of Organic Chemistry USSR (English Translation),1989,vol. 25,p. 1611 - 1615
Zhurnal Organicheskoi Khimii,1989,vol. 25,p. 1783 - 1788

11
[ 2014-83-7 ]
[ 1214-39-7 ]
[ 125486-31-9 ]

Reference： [1]Journal of Organic Chemistry USSR (English Translation),1989,vol. 25,p. 1611 - 1615
Zhurnal Organicheskoi Khimii,1989,vol. 25,p. 1783 - 1788

12
[ 2014-83-7 ]
[ 1214-39-7 ]
[ 125486-33-1 ]
[ 125486-35-3 ]

Reference： [1]Journal of Organic Chemistry USSR (English Translation),1989,vol. 25,p. 1611 - 1615
Zhurnal Organicheskoi Khimii,1989,vol. 25,p. 1783 - 1788

13
[ 487-89-8 ]
[ 2014-83-7 ]
[ 93548-80-2 ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 4307 - 4316
[2]Chemical and Pharmaceutical Bulletin,2012,vol. 60,p. 1037 - 1045
[3]Archiv der Pharmazie,2012,vol. 345,p. 812 - 821,10
[4]European Journal of Medicinal Chemistry,2012,vol. 57,p. 162 - 175

14
[ 6306-60-1 ]
[ 2014-83-7 ]
[ 59666-94-3 ]

Reference： [1]Journal of Medicinal Chemistry,1977,vol. 20,p. 1511 - 1516

15
[ 2014-83-7 ]
alkali cyanide [ No CAS ]
[ 3215-64-3 ]

Reference： [1]Ind. chim. belge Sonderband 31. Congr. int. Chim. ind. Luettich 1958 Bd. 2, S. 463,

16
[ 2014-83-7 ]
[ 68-12-2 ]
[ 20973-90-4 ]

Yield	Reaction Conditions	Operation in experiment
62%		A 200-mL three-necked flask equipped with a thermometer, a dropping funnel, a three-way stopcock, and a mechanical stirrer was purged with nitrogen. Thereto, were added 1.85 g (76 mmol) of magnesium, and 30 mL of diethyl ether. The dropping funnel was filled with a solution of 13.5 g (69 mmol) of 2,6-dichlorobenzyl chloride (produced by Tokyo Kasei K.K.) in 40 mL of diethyl ether. The solution was added dropwise into the flask by keeping the temperature of the reaction system at about 300 C. Thereafter, the reaction mixture was aged at room temperature for 30 minutes, and cooled with ice. Thereto, 6 g (82 mmol) of N,N-dimethylformamide was added dropwise. The reaction mixture was aged at room temperature for one hour, cooled with ice, and poured into 50 mL of 3N hydrochloric acid solution. The mixture was allowed to separate into phases, and the separated matter was extracted with diethyl ether. The combined organic phase was dried over anhydrous sodium sulfate. After filtration and concentration, 5 mL of methyl t-butyl ether was added to the concentration residue, and the mixture was heated to dissolve the residue. After cooling of the solution to room temperature, the deposited crystalline matter was collected by filtration to obtain 8.1 g (43 mmol) of crystalline 2,6-dichlorophenylacetaldehyde. (Yield: 62%)

Reference： [1]Tetrahedron Letters,1999,vol. 40,p. 8837 - 8840
[2]Patent: US6346621,2002,B1 .Location in patent: Page column 15

17
[ 20595-30-6 ]
[ 2014-83-7 ]
[ 271573-30-9 ]
(S)-7-(2,6-Dichloro-benzyloxy)-2-[(E)-3-(3-fluoro-phenyl)-acryloyl]-6,8-diiodo-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2000,vol. 10,p. 649 - 652

18
[ 779-89-5 ]
[ 2014-83-7 ]
[ 271573-30-9 ]
(S)-7-(2,6-Dichloro-benzyloxy)-6,8-diiodo-2-[(E)-3-(3-trifluoromethyl-phenyl)-acryloyl]-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2000,vol. 10,p. 649 - 652

19
[ 2014-83-7 ]
[ 938-55-6 ]
[ 125486-36-4 ]

Reference： [1]Chemistry of Heterocyclic Compounds,2001,vol. 37,p. 743 - 746

20
[ 37169-36-1 ]
[ 2014-83-7 ]
[ 232276-39-0 ]
2-<i>tert</i>-butoxycarbonylamino-3-[3-(2,6-dichloro-benzyloxy)-4-hydroxy-phenyl]-propionic acid methyl ester [ No CAS ]
N-(tert-butoxycarbonyl)-3,4-bis(2,6-dichlorobenzyloxy)-L-phenylalanine methyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2002,vol. 10,p. 2051 - 2066

21
[ 2014-83-7 ]
[ 55758-32-2 ]
[ 836652-81-4 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 414 - 426

22
[ 2014-83-7 ]
[ 24985-85-1 ]
[ 313951-92-7 ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 5 - 8

23
[ 2014-83-7 ]
3-(2,6-dichlorobenzyl)-1-(2-methylbenzyl)pyrrolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%		To a mixture of 1-(2-methylbenzyl)pyrrolidin-2-one obtained in Reference Example 1A (0.50 g) and tetrahydrofuran (10 mL) was added lithium diisopropylamide (tetrahydrofuran solution, 2 M, 1.32 mL) at -78C under nitrogen atmosphere, and the mixture was stirred for 10 min. A solution of alpha,2,6-trichlorotoluene (0.52 g) in tetrahydrofuran (5 mL) was added to the obtained solution, and the mixture was further stirred at -78C for 10 min, and allowed to warm to room temperature. 10% Aqueous ammonium chloride was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was subjected to silica gel column chromatography (hexane-ethyl acetate 9:1-4:1) to give the title compound (0.74 g, 80%) as a colorless solid. 1H NMR (300 MHz, CDCl3) delta ppm 1.83-1.98 (m, 2 H), 2.33 (s, 3 H), 2.91-3.12 (m, 3 H), 3.13-3.30 (m, 1 H), 3.43-3.63 (m, 1 H), 4.51 (s, 2 H), 7.04-7.14 (m, 1 H), 7.14-7.23 (m, 4 H), 7.27-7.35 (m, 2 H).

Reference： [1]Patent: EP1864971,2007,A1 .Location in patent: Page/Page column 141

24
1-cyclohexyl-3-(methylamino)pyrrolidin-2-one hydrochloride [ No CAS ]
[ 2014-83-7 ]
1-cyclohexyl-3-[N-(2,6-dichlorobenzyl)-N-methylamino]pyrrolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 20℃; for 16h;	A mixture of 1-cyclohexyl-3-(methylamino)pyrrolidin-2-one hydrochloride obtained in Example 93A (0.23 g), alpha, 2, 6-trichlorotoluene (0.22 g), potassium carbonate (0.29 g), potassium iodide (0.18 g) and N,N-dimethylformamide (10 mL) was stirred at room temperature for 16 hr. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was subjected to NH-silica gel column chromatography (hexane-ethyl acetate 9:1) to give the title compound (0.32 g, 90%) as a colorless solid. 1H NMR (300 MHz, CDCl3) delta ppm 0.97-1.21 (m, 1 H), 1.25-1.51 (m, 4 H), 1.62-1.88 (m, 5 H), 1.98-2.28 (m, 2 H), 2. 33 (s, 3 H), 3.18-3.41 (m, 2 H), 3.70 (dd, J=9.0, 7.9 Hz, 1 H), 3.90-4.05 (m, 1 H), 4.05-4.13 (m, 1 H), 4.17-4.25 (m, 1 H), 7.08-7.18 (m, 1 H), 7.27-7.33 (m, 2 H).

Reference： [1]Patent: EP1864971,2007,A1 .Location in patent: Page/Page column 172

25
[ 2014-83-7 ]
methyl 1-cyclohexyl-3-(2,6-dichlorobenzyl)-2-oxopyrrolidine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%		To a solution of methyl 1-cyclohexyl-2-oxopyrrolidine-3-carboxylate obtained in Reference Example 13A (3.0 g) in tetrahydrofuran (40 mL) was added sodium hydride (60% oil; 0.56 g) by small portions under ice-cooling. This mixture was stirred at 0C for 1 hr, alpha,2,6-trichlorotoluene (3.12 g) was added, and the reaction mixture was further stirred at room temperature for 4 hr. Saturated aqueous ammonium chloride was added to the reaction mixture under ice-cooling, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was subjected to silica gel column chromatography (hexane-ethyl acetate 4:1-7:3) to give the title compound (2.83 g, 55%) as a white solid. Recrystallization from ethyl acetate-ether gave colorless crystals (1.36 g). 1H NMR (300 MHz, CDCl3) delta ppm 1.00-1.12 (m, 1 H), 1.20-1.45 (m, 4 H), 1.64-1.87 (m, 6 H), 2.36-2.44 (m, 1 H), 2.90-2.97 (m, 1 H), 3.20-3.28 (m, 1 H), 3.72-3.99 (m, 3 H), 3.77 (s, 3 H), 7.12 (t, J=8.1 Hz, 1 H), 7.29 (d, J=7.8 Hz, 2 H).

Reference： [1]Patent: EP1864971,2007,A1 .Location in patent: Page/Page column 188-189

26
[ 194851-16-6 ]
[ 2014-83-7 ]
[ 832114-34-8 ]

Yield	Reaction Conditions	Operation in experiment
61%	With sodium hydride; In N,N-dimethyl-formamide; at 0 - 20℃; for 0.166667h;	To a solution of the compound from 6D (113 mg, 0.5 mmol) in dry DMF (2 ml) was added sodium hydride (20 mg). The solution was cooled down to 0 C. and 2,6-dichlorobenzy chloride (100 mg, 0.0) was added. Then the mixture was allowed to react at room temperature for 10 min. after adding water (4 ml), the precipitate was filtrated and washed with water and dried in air. 117 mg of desired product was obtained (yield: 61%). HPLC (4 minute gradient) tR=3.11 min; MS m/z 383.40, 385.13, 386.93 (M+H]+

Reference： [1]Patent: US2005/20590,2005,A1 .Location in patent: Page/Page column 23-24

27
[ 37169-36-1 ]
[ 2014-83-7 ]
N-(tert-butoxycarbonyl)-3,4-bis(2,6-dichlorobenzyloxy)-L-phenylalanine methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With n-Bu4NI; potassium carbonate; In N,N-dimethyl-formamide;	2) 2,6-Dichlorobenzyl chloride (1.73 g) was added to a suspension of N-(tert-butoxycarbonyl)-3,4-dihydroxy-L-phenylalanine methyl ester (2.5 g), K2CO3 (2.22 g), and n-Bu4NI (0.297 g) in DMF (15 mL) at room temperature. The mixture was stirred overnight at room temperature, diluted with water and extracted with ether. The extract was dried (MgSO4) and evaporated. The residue was purified by column chromatography (silica gel; eluent: hexanes/CH2Cl2/EtOAc, 5:5:1) to yield N-(tert-butoxycarbonyl)-3,4-bis(2,6-dichlorobenzyloxy)-L-phenylalanine methyl ester (2.0 g), ESMS: m/z 630 (MH+), N-(tert-butoxycarbonyl)-3-(2,6-dichlorobenzyloxy) -4-hydroxy-L-phenylalanine methyl ester (0.39 g), ESMS: m/z 470 (MH+), and N-(tert-butoxycarbonyl)-4-(2,6-dichlorobenzyloxy)-3-hydroxy-L-phenylalanine methyl ester (0.45 g), ESMS: m/z 470 (MH+), respectively.

Reference： [1]Patent: US6521666,2003,B1

28
[ 2014-83-7 ]
[ 17536-38-8 ]
[ 163688-35-5 ]

Yield	Reaction Conditions	Operation in experiment
68%	With NaH; In N,N-dimethyl-formamide; mineral oil;	A. 1-(2,6-Dichlorophenylmethyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid ethyl ester. A suspension of 80 mg (2 mmol) of 60% NaH/mineral oil was washed with hexane and placed in 8 mL of DMF. With ice-bath cooling, 494 mg (2 mmol) of 5-methoxy-2-methyl-1H-indole-3-acetic acid ethyl ester was added and stirred 1 hour, then 391 mg (2 mmol) of alpha,2,6-trichlorotoluene was added and stirring maintained for 1.5 hours. The mixture was diluted with water, extracted with EtOAc, the EtOAc solution washed with water/NaCl, and dried (MgSO4). The solution was concentrated at reduced pressure, and the product chromatographed on silica, eluding with 25% EtOAc/hexane to give 556 mg (68% yield) of 1-(2,6-dichlorophenylmethyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid ethyl ester, which solidified on standing, melting point, 131-133 C. Analyses: Calc'd for C21 H21 Cl2 NO3: C, 62.08; H, 5.21; N, 3.45. Found: C, 61.79; H, 5.23; N, 3.51.

Reference： [1]Patent: US5684034,1997,A

29
[ 151-50-8 ]
[ 2014-83-7 ]
[ 3215-64-3 ]

Yield	Reaction Conditions	Operation in experiment
95%	With 18-crown-6 ether; In ethanol; water; for 1 - 3h;Heating / reflux;	EXAMPLE 13-(2,6-DichIoro-phenyl)-6-(2,4-difluoro-phenyIamino)-l-niethyl-pyrazolo[l,5-a]pyrimidin-2-one:Step l(2,6-DichIorophenyI)-acetonitrile: A 500 mL round-bottom flask was charged with a solution of KCN (26 g, 400.00 mmol) ,18-crown-6 (0.05 g) in water (60 ml). To this was added 1 ,3-dichloro-2- (chloromethyl)benzene (40 g, 206.24 mmol) in ethanol (300 ml). The resulting solution was allowed to stir for 1~3 hours while the temperature was maintained at reflux. The reaction progress was monitored by TLC (AcOEt: PE=I :4). The mixture was the concentrated to dryness on a rotary evaporator. The resulting residue was the transferred into a seperatory funnel, washed with water (5 x 100 mL) to afford 35.4 g (95%) of 2-(2,6-dichlorophenyl)acetonitrile as a white solid. This product was used without further purification.

Reference： [1]Patent: WO2007/15866,2007,A2 .Location in patent: Page/Page column 29; 31

30
[ 1008474-12-1 ]
[ 2014-83-7 ]
[ 1008474-14-3 ]

Yield	Reaction Conditions	Operation in experiment
28%	With potassium tert-butylate; In tetrahydrofuran; at 55℃; for 24h;	1-(2-Phenylpropyl)-4-oxo-piperidine O-(2,6-dichloro-benzyl)-oxime (49): 1.22 g (6.25 mmol) 2,6-dichlorobenzylchloride, 1.20 g (5.0 mmol) 1-(3-phenylpropyl)piperidin-4-oxime and 0.71 g (6.25 mmol) potassium-tert-butoxide were dissolved in dry 100 mL THF and stirred for 24 h at 55C in the dark under Ar. The solvent was evaporated and the residue was diluted with 100 mL dichloromethane and 50 mL 2.0 M NaOH. The layers were separated and aqueous layer extracted with dichloromethane (2 x 80 mL). The combined organic layers were dried and evaporated to achieve a colorless solid. Yield: 0.68 g (28%). C21H24N2OCl2 (391.3 g/mol); 1H NMR (CDCl3, delta = ppm): 7. 13 - 7.04 (8 H, m, aromatic); 5.23 (2 H, s, O-CH2), 2.58 - 2.42 (8 H, m, 2-H, 3-H, 5-H, 6-H); 2.41 - 2.31 (4 H, m, Ph-CH2-CH2-CH2-N); 1.82 - 1.77 (2 H, m, Ph-CH2-CH2-CH2-N). 13C NMR (CDCl3, delta = ppm): 152.1 (-C=N), 136.1 (C-1'), 133.4 (C-1'), 130.2 (C-2', C-6'), 128.5, 128.4, 128.2 (C-2', C-3' C-5', C-6', C-3', C-5''), 125.8, 125.6 (C-4', C-4''), 57.5 (CH2-O), 53.4 (Ph-CH2-CH2-CH2-N), 52.4 (Ph-CH2-CH2-CH2-N), 40.7 (C-2, C-6), 33.6 (C-3, C-5), 31.1 (Ph-CH2-CH2-CH2-N). IR (ATR, cm-1): 3026 (=C-H); 2945 and 2812 (-CH2), 1660 (-C=N), 1563 (-C=C- arom.), 739, 705, 700, 642 (out of plane). mp. 147 C.

Reference： [1]Patent: EP2036556,2009,A1 .Location in patent: Page/Page column 12
[2]Journal of Medicinal Chemistry,2008,vol. 51,p. 238 - 250

31
[ 2014-83-7 ]
[ 51828-02-5 ]
[ 1029538-19-9 ]

Yield	Reaction Conditions	Operation in experiment
76%	With triethylamine; In acetonitrile; at 160℃; for 0.25h;Microwave irradiation;	2,4-Dichlorobenzyle bromide (72 mg, 0.30 mmol), triethylamine (33 ?L, 0.24 mmol) and 3-phenyl-6,7,8,9-tetrahydro-5H-imidazo[l,2-a]azepine (50 mg, 0.24 mmol) in 1 mL dry acetonitrile were microwave irradiated at 160 0C for 15 min. The reaction mixtures were evaporated to dryness. The dried residue was triturated with Et2? and evaporated to dryness. The residue was dissolved in H2O/MeOH 95:5, washed with Et2? (limited amounts of brine was added to the water phase) and extracted with CH2Cl2. The organic phase was dried over Na2SO4, filtrated and evaporated to dryness which gave the title compound (73 mg, 76%). 1H NMR (CDCl3) delta: 7.45-7.38 (m, 5H); 7.36-7.28 (m, 3H); 6.81 (s, IH); 5.72 (s, 2H); 4.35-4.31 (m, 2H); 3.72-3.66 (m, 2H); 2.06-1.98 (m, 2H); 1.89-1.82 (m, 2H); 1.81-1.74 (m, 2H). 13C NMR (CDCl3) delta: 150.4; 136.7; 135.0; 132.1; 130.6; 130.0; 129.3; 129.3; 128.9; 125.0; 117.0; 47.9; 47.8; 29.1; 27.0; 25.6; 23.9. Purity by LC/MS (UV/MS): 100/95.

Reference： [1]Patent: WO2008/64136,2008,A2 .Location in patent: Page/Page column 48-49

32
[ 1008474-15-4 ]
[ 2014-83-7 ]
4-[(2,6-dichloro-benzyloxyimino)-methyl]-1-(3-phenyl-propyl)-piperidinium hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%		The oxime 52 (0.7 g, 2.84 mmol) was dissolved in 40 mL abs. MeOH and potassium tert.-butoxide was added. The solution was stirred at 25 C for 3 h and the solvent was removed in vacuo. The residue was suspended in 50 mL dry acetonitrile and 0.56 g (2.84 mmol) 2,6-dichlorobenzylchloride was added. The solution was refluxed for 2 h and the solvent was removed in vacuo. Column chromatography (silica gel, eluent: EtAc/EtOH 1:1 + 0.7 % triethylamine) gave a colorless oil. This oil dissolved in 10 mL diethyl ether and 1 mL 1.0 M hydrochloric acid in methanol was added. After 12 h at 4 C a colorless solid was isolated. Yield: 0.51 g (40 %). C22H27Cl3N2O (412.5 g/mol); 1H NMR (d6-DMSO, delta ppm, J = Hz): 10.28 (1 H, br, NH+), 7 . 50 - 7.18 (9 H, HC=N, 8 H arom.), 5.23 (2 H, s, CH2-O), 3.58 - 3.38 (2 H, m, 2-Heq, 6-Heq), 3.00 - 2.80 (4 H, m, Ph-CH2-CH2-CH2-N, 2-Hax, 6-Hax), 2.61 (2 H, t, J = 7.6, Ph-CH2-CH2-CH2-N), 2.41 - 2.37 (1 H, m, 4-H), 2.00 - 1.68 (6 H, m, 3-H, 5-H, Ph-CH2-CH2-CH2-N) . 13C NMR (d6-DMSO, delta=ppm) : 153.0 (C=N), 140.5 (C-1'), 136.1 (C-2'', C-6''), 132.0 (C-1''), 131.2 (C-4''), 128.6, 128.4, 128.2 (C-2', C-3', C-5', C-6', C-3'', C-5''), 126.1 (C-4'), 69.4 (CH2-O), 55.6 (Ph-CH2-CH2-CH2-N), 50.9 (C-2, C-6), 33.8 (C-4), 32.0 (Ph-CH2-CH2-CH2-N), 26.0 (C-3, C-5), 24.8 (Ph-CH2-CH2-CH2-N+). IR (ATR, cm-1): 2910 (-CH), 2512 (NH+) 1715 (C=N), 1599 and 1563 (C=C, arom.), 1021 (C-O), 931 (N-O), 777, 767, 753 and 698 cm-1 (out of plane), Mp.: 198 C (dec).

Reference： [1]Patent: EP2036556,2009,A1 .Location in patent: Page/Page column 13

33
[ 1105713-22-1 ]
[ 2014-83-7 ]
[ 1191992-47-8 ]

Yield	Reaction Conditions	Operation in experiment
13.1%		Example P3: Preparation of S-difluoromethyl-i-methyl-I H-pyrazole^-carboxylic acid [2- (2,6-dichloro-benzyloxy)-1-methyl-ethyl1-amide (compound 1.197): To a suspension of sodium hydride 50% in oil (10mg; 0.39mmol) in dimethylformamide (3ml) sodium hydride 50% in oil (0.12g; 2.5mmol) is added 3-difluoromethyl-1-methyl-1 H- pyrazole-4-carboxylic acid (2-hydroxy-1-methyl-ethyl)-amide (90mg; 0.39mmol), prepared as described in example P4 via syringe at ambient temperature. The reaction mixture is stirred for 20 minutes at ambient temperature followed by the addition of 1 ,3-dichloro-2- <n="24"/>chloromethyl-benzene (78mg; 0.40mmol). The reaction mixture is stirred for 15 hours at ambient temperature then poured onto 1 M HCI (20ml) and extracted with ethyl acetate (2x20ml). The combined ethyl acetate layers are washed with water (20ml), brine (20ml) and then dried over Na2SO4. After removal of the solvent the residue (152mg oil) is purified by flash chromatography twice over silica gel (eluent: cyclo hexane/ethyl acetate 1 :9 followed by eluent dichloromethane/methanol 19:1 ). 20mg (13.1 % of theory) of 3- difluoromethyl-1-methyl-1 H-pyrazole-4-carboxylic acid [2-(2,6-dichloro-benzyloxy)-1-methyl- ethyl]-amide (compound 1.197) is obtained in form of an oil. 1H NMR (400MHz, CDCI3): delta 1.37-1.39(d,3H, CH3), 3.52-3.58(m,2H,CH2), 3.91 (s,3H,CH3),4.32-4.41 (m,1 H, CH), 4.59(s,2H,CH2),6.57(s,1 H, NH), 6.71-6.97(t,1 H, CHF2),7.23(dxd,1 H,Ar-H),7.36(d,1 H,Ar-H),7.42(d,1 H,Ar-H),7.88(t,1 H1Py-H). MS [M+H]+ 392/394/396.

Reference： [1]Patent: WO2009/127718,2009,A2 .Location in patent: Page/Page column 22-23

34
[ 110-85-0 ]
[ 2014-83-7 ]
[ 102292-50-2 ]

Yield	Reaction Conditions	Operation in experiment
95.7%	In tetrahydrofuran; for 4h;Reflux;	General procedure: Anhydrous piperazine (6.89 g, 80 mmol) was dissolved in 40 mL of freshly distilled THF. Once the piperazine was fully dissolved, 2.303 mL (20 mmol) of benzyl chloride was added dropwise. The reaction mixture was then refluxed for about 4 h until benzyl chloride disappeared, as assessed by TLC. The stirring mixture was allowed to cool, and then filtered. The filtrate was concentrated in a rotary evaporator and then diluted with EtOAc (100 mL) and water (50 mL), which was then made basic (pH>12) with a saturated 1 N NaOH aqueous solution and separated. The organic phase was washed with water (4 × 100 mL), brine (2 × 100 mL), dried over Na2SO4 and concentrated to yield an oil. Column chromatography (PE/EtOAc = 1:1 to EtOAc/MeOH = 5:1) afforded a pale yellow liquid.

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 1404 - 1414
[2]Bioorganic Chemistry,2019,vol. 90

35
[ 501-94-0 ]
[ 2014-83-7 ]
[ 1334930-83-4 ]

Yield	Reaction Conditions	Operation in experiment
91%	With potassium carbonate; In acetone; for 24h;Reflux;	General procedure: To a solution of 4-(2-hydroxyethyl)phenol 5 (6.9 g, 0.05 mol) and K2CO3 (10.35 g, 0.075 mol) in acetone (50 mL), 4a-c (0.05 mol) was added. The suspension was stirred vigorously, and heated to reflux for 24 h. On cooling the reaction mixture down to room temperature, the suspension was concentrated and diluted with water (200 mL) and then extracted with EtOAc (2 × 100 mL). The organic layers was washed with 10% NaOH solution, dried with Na2SO4 and then concentrated in vacuo to afford 6a-c.

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3551 - 3563

36
[ 120-47-8 ]
[ 2014-83-7 ]
[ 149288-99-3 ]

Yield	Reaction Conditions	Operation in experiment
92.2%	With potassium carbonate; In acetone; for 24h;Reflux;	To a solution of ethyl 4-hydroxybenzoate 12 (5.81 g, 0.035 mol) and K2CO3 (9.6 g, 0.07 mol) in acetone (80 mL), 3 (6.86 g, 0.035 mol) was added. The suspension was stirred vigorously, and heated to reflux for 24 h. On cooling the reaction mixture down to room temperature, the suspension was concentrated and diluted with water (100 mL) and then extracted with AcOEt (2 × 100 mL). The organic layers was washed with 10% NaOH solution (100 mL), dried with Na2SO4 and then concentrated in vacuo to afford 13 as a white solid (10.52 g, 92.20%). Mp 84-85 C. 1H-NMR (300 MHz, CDCl3): delta 1.36-1.40 (t, J = 7.2 Hz, 3H, CH3), 4.32-4.39 (q, J = 7.2 Hz, 2H, CH2), 5.32 (s, 2H, CH2), 7.02-7.05 (d, J = 8.7 Hz, 2H, Ar), 7.23-7.28 (t, J = 7.2 Hz, 1H, Ar), 7.36-7.38 (d, J = 7.2 Hz, 2H, Ar), 8.02-8.04 (d, J = 8.7 Hz, 2H, Ar); EI-MS (m/z): 324 (M)+.
		A mixture of 4-hydroxybenzoic acid ethyl ester (3.00 g,18.1 mmol), KOH (1.52 g, 27.1 mmol) and 40 mL of acetonitrilewas heated to reflux for 0.5h. Alkyl bromide or benzylchloride derivative (21.6 mmol) was added drop-wise to themixture. The mixture was heated under reflux for 3 h afterthe completion of reaction, the mixture was poured into 100mL of water. Aqueous layer was extracted with dichloromethane(30 mL 3). The organic layer was separated, driedover anhydrous MgSO4 and then evaporated to obtain thecrude product.

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 49,p. 164 - 171
[2]Letters in drug design and discovery,2014,vol. 11,p. 628 - 635

37
[ 103-90-2 ]
[ 2014-83-7 ]
[ 903294-07-5 ]

Yield	Reaction Conditions	Operation in experiment
92.2%	With potassium carbonate; In acetone; for 24h;Reflux;	To a solution of 4-acetamino phenol 22 (4.9 g, 0.03 mol) and K2CO3 (8.28 g, 0.06 mol) in acetone (80 mL), 3 (6.46 g, 0.033 mol) was added. The mixture was stirred vigorously, and heated to reflux for 24 h. On cooling the reaction mixture down to room temperature, the mixture was concentrated and diluted with water (100 mL) and then extracted with EtOAc (2 × 100 mL). The organic layers was washed with 10% NaOH solution (100 mL), dried with Na2SO4 and then concentrated in vacuo to afford 23 (10.52 g, 92.20%) as a white solid. m.p. 185-187 C. EI-MS (m/z): 309 (M)+.

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 49,p. 164 - 171

38
[ 2014-83-7 ]
[ 99-93-4 ]
[ 695157-31-4 ]

Yield	Reaction Conditions	Operation in experiment
99.3%	With potassium carbonate; In acetone; for 24h;Reflux;	To a solution of 1-(4-hydroxyphenyl)ethanone 4 (6.8 g, 0.05 mol) and K2CO3 (13.8 g, 0.1 mol) in acetone (100 mL), 2.6-dichlorobenzyl chloride 3 (10.78 g, 0.055 mol) was added. The mixture was stirred vigorously, and heated to reflux for 24 h. On cooling the reaction mixture to room temperature without down, the mixture was concentrated and diluted with water (100 mL) and then extracted with AcOEt (2 × 50 mL). The organic layer was washed with 10% NaOH solution (50 mL), dried with Na2SO4 and then concentrated in vacuo to afford 1-(4-(2,6-dichlorobenzyloxy)phenyl)ethanone 5 (14.65 g, 99.3%) as a white solid. m.p.130-132 C. 1H-NMR (300 MHz, CDCl3):delta 2.51 (3H, s, CH3), 5.28 (2H, s, CH2), 6.99 (2H, d, J = 8.7 Hz, ArH), 7.22 (1H, m, ArH), 7.32 (2H, d, J = 7.5 Hz, ArH), 7.91 (2H, d, J = 8.7 Hz, ArH). EI-MS (m/z): 294 (M)+.

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 49,p. 164 - 171
[2]Molecular Diversity,2019

39
[ 2014-83-7 ]
[ 24155-42-8 ]
isoconazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%		To a suspension of 60% dispersion of NaHin mineral oil (0.25 g, 7.5 mmol) in dry 1,4-dioxane (15 mL) atroom temperature under a nitrogen atmosphere was added dropwisea solution of 13 (1.28 g, 5 mmol) in 1,4-dioxane (20 mL).The reaction mixture was refluxed for 1 h. 1,3-Dichloro-2-(chloromethyl)benzene 14 (1 g, 5 mmol) was added dropwise and refluxedfor 2.5 h. Solvent was removed in vacuum, and after thatthe reaction was quenched with water (100 mL). The aqueous solutionwas extracted with ethyl acetate (3x50 mL), the organicphases were combined, dried over anhydrous Na2SO4, and filtered.The solvent was removed by distillation under reduced pressure,giving a crude reaction mixture that was purified followed by crystallizationfrom acetone to give 1.45 g of ester 10. Yield: 70%. M.p.115-116 C.A solution of base 10 (1.2 g, 2.8 mmol) in acetone (5 mL) wastreated with concentrated (86%) HNO3 (5 mL) followed by stirringfor 12 h. The white solid 15 was filtered and dried over P2O5 in vacuumdesiccator. Yield 1.35 g, 98%. M.p. 203-204 C. IR (KBr, cm 1):1381 (w), 1380 (w), 1510 (m), 1150 (m), 810 (s), 720 (s). 1H NMR(DMSO-d6, ppm): d = 4.40-4.50 (m, 2 H, 1CH), 4.62 (d, J = 10.8 Hz, 2H, -OCH2), 5.12-5.20 (m, 1 H, 2CH), 7.30-7.42 (m, 3 H, phenyl of 2-(2,6-dichlorobenzyloxy)), 7.48-7.59 (m, 2 H, 5CH, 6CH), 7.60 (s, 2 H,4CH, 5CH of the imidazole ring), 7.72 (s, 1 H, 3CH) 9.04 (s, 1 H, 2CHof the imidazole ring), 14.6 (s, 1 H, HNO3). 13C NMR (DMSO-d6,ppm): d = 138.10 (1C), 137.79 (13C), 135.35 (6C), 133.12 (14C, 7C),131.88 (10C), 131.22 (2C), 130.00 (16C), 129.41 (7C), 128.21 (8C),128.16 (15C, 18C) 127.13 (11C), 125.18 (9C), 118.29 (3C), 74.31(5C), 71.80 (12C), 50.99 (4C). Anal. Calc. for C18H15Cl4N3O4(479.14): C, 45.12; H, 3.16; N, 8.77; Found C, 45.40; H, 3.15%.

Reference： [1]Polyhedron,2013,vol. 52,p. 106 - 114

40
[ 75-15-0 ]
[ 28830-22-0 ]
[ 2014-83-7 ]
[ 1476040-02-4 ]

Yield	Reaction Conditions	Operation in experiment
80%		General procedure: To a stirred solution of tris(trimethylsilyl)methyllithium (1 mmol) in THF, carbon disulfide (1.2 mmol) in 2 ml THF was added at -46 C (cyclohexanone/N2) under argon atmosphere. The mixture is stirred for 5min and then benzyl halide (1 mmol) (for compound 8, 0.5mmol of 1,4-bis(iodomethyl)benzene) is added at this temperature and the stirring is maintained (-46 C?0 C) to end of the reaction that followed by TLC. The mixture is poured into water and extracted with CH2Cl2. The organic layer was washed with water, dried with Na2SO4 and filtered. The solvent was evaporated and the residue was purified by preparative TLC on silica gel using n-hexane as eluent to give the product.

Reference： [1]Journal of Organometallic Chemistry,2013,vol. 745-746,p. 214 - 218

41
[ 2014-83-7 ]
[ 2948-92-7 ]
1-(2,6-dichlorobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole dihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34%		General procedure: 1-(4-Chlorobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole dihydrochloride (1). Under an atmosphere of nitrogen, compound 36 (250 mg, 1.24 mmol, 1 equiv) was dissolved in freshly distilled warm tetrahydrofuran (THF) (2.5 mL), then cooled to 0 C. To this solution was added 60% NaH in oil (100 mg, 60 mg pure, 2.48 mmol, 2 equiv) and the mixture stirred at 0 C for 5 min. 4-Chlorobenzyl bromide (255 mg, 1.24 mmol, 1 equiv) was added followed by the addition of tetra-n-butylammonium bromide (23 mg, 0.07 mmol, 6 mol %). The mixture was stirred at rt overnight, then diluted with a solution of water (2 drops) in THF (5 mL). The solution was filtered through Celite, and the Celite was washed with THF (50 mL) and then EtOAc (50 mL). The filtrate was concentrated and the remaining residue purified by flash column chromatography on silica gel (EtOAc) to give the free base (195 mg) as an oil (Rf = 0.46, EtOAc). To a solution of the free base in MeOH (2 mL) was added a solution of 37% aqueous HCl (158 mg, 1.60 mmol, 2.7 equiv) in MeOH (2 mL). The mixture was concentrated, Et2O (5 mL) was added, and the mixture concentrated again. High-vacuum drying gave the product (242 mg, 0.61 mmol, 49%) as a white solid

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 6788 - 6795

42
[ 1564274-98-1 ]
[ 2014-83-7 ]
[ 1564274-93-6 ]

Yield	Reaction Conditions	Operation in experiment
65%		General procedure: Sodium methylate (5 mmol, 0.27 g) and 6-(4H-1,2,4-triazol-4-yl)-3,4-dihydroquinolin-2(1H)-one (4) (5 mmol, 1.1 g) were dissolvedin acetonitrile (50 mL) and refluxed for 1 h. Then the appropriate alkyl bromide or benzyl chloride (6 mmol) was added to the mixture. The reaction mixture was heated at reflux temperature for 2-4 h. After removing half of the solvent, 100 mL ofwater was poured into the flask and the precipitate formed was filtered, which was recrystallized in ethanol (or mix of ether and dichloromethane) to produce a white solid. The yield, melting pointand spectral data of each compound were given below.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 73,p. 217 - 224

43
[ 2014-83-7 ]
N,N'-methylene-di(2-amino-5-mercapto-1,3,4-thiadiazole) [ No CAS ]
[ 1516888-72-4 ]

Yield	Reaction Conditions	Operation in experiment
58%	With potassium hydroxide; In ethanol; at 20 - 50℃; for 8h;	General procedure: To a stirred solution of intermediate 2 (0.28 g, 1 mmol) in 20 mL 0.1mol/L potassium hydroxide solution, substituted benzyl chloride (2 mmol) in ethanol (2 mL) was slowly added at room temperature. The mixture was stirred and heated at 50 C for 8 h. The solvent was removed and the residue was purified by chromatography on silica gel (ethyl acetate/petroleum ether = v/v 1:1) to give the desired compound 3a to 3o.

Reference： [1]Phosphorus, Sulfur and Silicon and the Related Elements,2014,vol. 189,p. 134 - 142

44
[ 2014-83-7 ]
[ 128564-78-3 ]
[ 1621102-48-4 ]

Yield	Reaction Conditions	Operation in experiment
89%	In acetonitrile; at 60 - 70℃;	General procedure: To a mixture of (E)-3-(pyridin-4-ylmethylene)indolin-2-one (2,1 mmol) in dry acetonitrile (5 mL), proper benzyl bromide or chloride (1.5 mmol) was added and the mixture was stirred at 60-70 C for 6-24 h. Then, the mixture was cooled and the precipitated solid was filtrated off and washed with diethyl ether or n-hexane. The product was recrystallized from ethanol-water (1:1) to give pure compounds 3a-u.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 84,p. 375 - 381

45
[ 5597-50-2 ]
[ 2014-83-7 ]
methyl 3-(4-(2,6-dichlorobenzyloxy)-phenyl)propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89.8%	With potassium carbonate; In acetone; for 24h;Reflux;	To a solution of methyl 3-(4-hydroxyphenyl)propanoate2 (18 g, 0.1 mol) and K2CO3 (20.7 g, 0.15 mol) in acetone(200 mL), 2, 6-dichlorobenzyl chloride 1 (19.6 g, 0.1 mol)was added. The mixture was stirred vigorously, and heated to reflux for 24 h. On cooling the reaction mixture down to room temperature, the mixture was concentrated and diluted with water (200 mL) and then extracted with AcOEt (2 x 100mL). The organic layers were washed with 10% NaOH solution,dried with Na2SO4 and then concentrated in vacuo to afford 3 (30.45 g, 89.8%) as a yellow oil. 1H-NMR (300MHz, CDCl3): 2.58-2.63 (2H, t, J = 7.5 Hz, J = 8.1 Hz, -CH2), 2.88-2.93 (2H, t, J = 7.5 Hz, J=8.1 Hz, -CH2), 3.66(3H, s, -CH3), 5.23 (2H, s, -CH2), 6.93-6.96 (2H, d, J = 8.7Hz, AA?BB?, Ar-H), 7.11-7.12 (2H, d, J = 6.6 Hz, Ar-H),7.19-7.22 (1H, t, J = 6.6 Hz, Ar-H), 7.32-7.35 (2H, d,J = 8.7Hz, AA?BB?, Ar-H) ppm. EI-MS (m/z) 338 (M)+.

Reference： [1]Letters in drug design and discovery,2015,vol. 12,p. 29 - 37

46
[ 2014-83-7 ]
[ 7746-27-2 ]
6-bromo-1-(2,6-dichlorobenzyl)-3-methyl-1H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10.4 g	With potassium carbonate; In N,N-dimethyl-formamide; at 1 - 40℃; for 20h;	(1) Synthesis of 6-bromo-1-(2,6-dichlorobenzyl)-3-methyl-1H-indazole [1-1] (hereinafter referred to as a compound [1-1]) To a solution of <strong>[7746-27-2]6-bromo-3-methyl-1H-indazole</strong> (9.57 g), which was obtained by the method described in the document (JP 2009-528363 W), in N,N-dimethylformamide (100 mL), were added potassium carbonate (12.6 g) and 2,6-dichlorobenzyl chloride (9.79 g) and the mixture was stirred at room temperature for 20 hours. The reaction mixture was quenched with water, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the titled compound (10.4 g) as a white solid. 1H-NMR (400 MHz, CDCl3) delta: 7.55 (1H, s), 7.47 (1H, d, J = 8.5 Hz), 7.38 (2H, d, J = 8.1 Hz), 7.25 (1H, d, J = 5.9 Hz), 7.22-7.20 (1H, m), 5.66 (2H, s), 2.50 (3H, s).

Reference： [1]Patent: EP2878594,2015,A1 .Location in patent: Paragraph 0373-0376

47
[ 3111-37-3 ]
[ 2014-83-7 ]
C₁₆H₁₃BrCl₂O₃ [ No CAS ]

Reference： [1]Archiv der Pharmazie,2015,vol. 348,p. 463 - 474

48
[ 2014-83-7 ]
[ 29490-19-5 ]
2-[(2,6-dichlorobenzyl)thio]-5-methyl-1,3,4-thiadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With triethylamine; In chloroform; at 20℃;Inert atmosphere;	10.5 ml (75.6 mmoles) of triethylamine were added dropwise at room temperature to a suspension under nitrogen atmosphere of lOg (75.6 mmoles) of 5-methyl-1,3,4-thiadiazole-2-thiol in 40 ml of chloroform; 14.8g (75.6 mmoles) of 1,3-dichloro-2-(chloromethyl)benzene, dissolved in 10 ml of chloroform were then added.Finally, additional 15.7 ml (0.11 moles) oftriethylamine were added dropwise.The mixture was left under stirring at room temperature for a night. After control in GC-MS and LCMS, the mixture was diluted with water and the phases were then separated; the aqueous phase was re-extracted twice with dichloromethane. The organic phases joinedtogether, were washed with water and a saturated solution of sodium chloride.After anhydrification on sodium sulfate, filtration and evaporation of the solvent at reduced pressure,19.8 g (68.0 mmoles) of the desired product wereobtained, as a yellow oil. Yield 90.0% LC-MS [M+H] =292.

Reference： [1]Patent: WO2016/42435,2016,A1 .Location in patent: Page/Page column 20

49
[ 2014-83-7 ]
[ 637-44-5 ]
2,6-dichlorobenzyl 3-phenylpropiolate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With copper(l) iodide; caesium carbonate; acetonitrile; at 60℃; for 24h;	General procedure: A mixture of benzyl halide (0.4 mmol), alkynoic acid (0.6 mmol), Cs2CO3 (2 equiv), CuI (10 mol%), and CH3CN (2 mL) in a tube was stirred in air at 60 C for 24 h. After that the mixture was poured into ethyl acetate, then washed with water, extracted with ethyl acetate, dried by anhydrous Na2SO4, then filtered and evaporated under vacuum, the residue was purified by flash column chromatography (petroleum ether or petroleum ether/ethyl acetate) to afford the corresponding coupling products. The characterization of the corresponding products was shown in Supporting Materials.

Reference： [1]Catalysis Letters,2016,vol. 146,p. 886 - 892

50
ethyl 3-((3-trityl-5-(tritylamino)-3H-[1,2,3]triazolo[4,5-b]pyridin-7-yl)thio)propanoate [ No CAS ]
[ 2014-83-7 ]
7-((2,6-dichlorobenzyl)thio)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%		[00187] KOtBu (12 mg, 0.11 mmol) was added to a solution of Intermediate 3 (40 mg, 0.05 3 mmol) in THF (1 mL). After stirring for 1 h, 1 ,3-dichloro-2-(chloromethyl)benzene(10 mg, 0.053 mmol) was added to the reaction mixture. The reaction mixture was stirred for 3 h. DCM (1 mL), TFA (2 mL) and triethysilane (0.048 mL, 0.030 mmol) were added to the reaction mixture and stirred for 20 mm at rt. The mixture was concentrated and purified by preparatory HPLC to yield Example 11(13 mg, 0.040 mmol, 75% yield). MS (ESI) 326.1 (M+H)+. ?H NMR (500 MHz, DMSO-d6) oe 7.57 (d, J8.0 Hz, 2H), 7.48 -7.37 (m, 1H), 6.61 (br. s., 1H), 4.71 (s, 2H).

Reference： [1]Patent: WO2016/40419,2016,A1 .Location in patent: Paragraph 00187

51
(4R,5R)-5-[(1S)-2-(benzyloxy)-1-hydroxyethyl]-4-vinyldihydrofuran-2(3H)-one [ No CAS ]
[ 2014-83-7 ]
(4S,5R)-5-{(1R)-2-(benzyloxy)-1-[(2,6-dichlorobenzyl)oxy]ethyl}-4-vinyldihydrofuran-2(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With tetra-(n-butyl)ammonium iodide; silver(l) oxide; In N,N-dimethyl-formamide; for 48h;Inert atmosphere; Darkness;	To a stirred solution of alcohol 42 (1.2 g, 4.58 mmol) in anhyd DMF (10 mL) were added Ag2O (1.8 g, 6.87 mmol), TBAI (3.38 g, 9.16 mmol), and 2,6-dichlorobenzyl chloride (1.78 g, 9.16 mmol) under an inert atmosphere, and the mixture was stirred for 48 h in darkness. When the reaction was complete, the mixture was filtered through Celite and extracted with EtOAc (30 mL) and cool H2O (15 mL). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure, and the residue was purified by column chromatography (hexanes-EtOAc, 9:1) to provide give a colorless oil; yield: 1.35 g (70%); molecular formula: C22H22Cl2O4; Rf = 0.5 (hexanes-EtOAc, 8:2). 1H NMR (400 MHz, CDCl3): delta = 7.38-7.30 (m, 7 H), 7.21 (dd, J = 8.67, 7.40 Hz, 1 H), 5.71 (dt, J = 17.10, 10.16, 8.37 Hz, 1 H), 5.09-4.95 (m, 2H), 4.83 (d, J = 10.50 Hz, 1 H), 4.62-4.53 (m, 2 H), 4.40 (dd, J = 6.80, 1.60 Hz, 1 H), 3.88 (dd, J = 8.82, 4.85 Hz, 1 H), 3.75-3.67 (m, 2 H), 3.17 (m, 1 H), 2.77 (dd, J = 17.60, 9.00 Hz, 1 H), 2.37 (dd, J = 17.60, 9.00 Hz, 2 H). 13C NMR (100 MHz, CDCl3): 176.0, 137.8, 136.8, 136.6, 132.9, 130.3, 128.5, 128.4, 127.8, 117.4, 83.4, 76.1, 73.6, 69.1, 67.1, 40.7, 34.9. MS (ES+): m/z = 437.6 [M + 17].

Reference： [1]Synthesis,2016,vol. 48,p. 1663 - 1683

52
[ 76894-56-9 ]
[ 2014-83-7 ]
1-(2,6-dichlorobenzyl)-3-[2-(4H-1,2,4-triazol-4-yl)ethyl]-1H-indole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With sodium hydride; In N,N-dimethyl-formamide; at 0℃; for 0.5h;	General procedure: To a solution of Compound 3 (2.1 g, 10 mmol) in DMF (30 ml) was added haloalkane (11 mmol) and NaH (1.66 g,12 mmol). After the reaction mixture was stirred at 0 C for 0.5 h, the mixture was added into 50 mL of ice-water and filtered to obtain a light white solid. Finally, they can be purified by chromatography on silica eluting with a gradient of methanol/dichloromethane (1:30) to give the compound 4a-t as solid.

Reference： [1]Letters in drug design and discovery,2016,vol. 13,p. 833 - 839

53
[ 2014-83-7 ]
[ 824-79-3 ]
1-(2,6-dichlorobenzyl)-2-(4-methylphenyl)disulfide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%		The 2,6-dichloro-yl benzyl chloride (195.5mg, 1.0mmol, 5.0equiv. ) And Na 2 S 2 O 3 · 5H 2 O (248.2mg, 1.0mmol, 5.0equiv. After) was added to the reaction tube, followed by addition of the reaction solvent of ethanol / water (0.25mL / 0.5mL), and stirred at a reaction temperature of 100 C for 2 hours. Then the reaction system was cooled, the solvent was removed under reduced pressure, followed by addition of p-toluene-sulfinate (35.6mg, 0.2mmol, 1.0equiv.), And then the reaction solvent was added 1,4-dioxane (1.0mL ), followed by stirring at a reaction temperature of 110 C for 11 hours. The reaction mixture was cooled to room temperature, then added DDQ (27.2mg, 0.12mmol, 0.6equiv.), At normal temperature for 4 hours post-treatment. Finally, the solvent was removed under reduced pressure The reaction solution, after column chromatography to give the product 12 (polar eluent: petroleum ether). Yield: Yield: 74%

Reference： [1]Patent: CN104387303,2016,B .Location in patent: Paragraph 0128-0131

54
[ 20277-69-4 ]
[ 2014-83-7 ]
1-(2,6-dichlorobenzyl)-2-methyldisulfide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%		The 3-trifluoromethyl benzyl chloride (195.5mg, 1.0mmol, 5.0equiv. ) And Na 2 S 2 O 3 · 5H 2 O (248.2mg, 1.0mmol, 5.0equiv. After) was added to the reaction tube, followed by addition of the reaction solvent of ethanol / water (0.25mL / 0.5mL), and stirred at a reaction temperature of 100 C for 2 hours. Then the reaction system was cooled, the solvent was removed under reduced pressure, followed by addition of sodium methylsulfinyl salt (20.5mg, 0.2mmol, 1.0equiv.), And then the reaction solvent was added 1,4-dioxane (1.0 mL), and stirred at a reaction temperature of 110 C for 11 hours. The reaction solution was cooled to room temperature. Was then added DDQ (27.2mg, 0.12mmol, 0.6equiv.), Stirred at room temperature for 4 hours, and finally the solvent was removed under reduced pressure to the reaction solution, after column chromatography to give the product 35 (polar eluent: ether stone ). Yield: 53%

Reference： [1]Patent: CN104387303,2016,B .Location in patent: Paragraph 0204-0207

55
5,6-dihydro[1,2,4]triazolo[3,4-a]isoquinolin-9-ol [ No CAS ]
[ 2014-83-7 ]
9-[(2,6-dichlorobenzyl)oxy]-5,6-dihydro[1,2,4]triazolo[3,4-a]isoquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59.8%	With sodium hydride; In N,N-dimethyl-formamide; at 20℃;	General procedure: Compound 4b (0.2 g, 1.1 mmol) was dissolved in anhydrous DMF (2 mL), alkyl bromide, or benzylchloride derivatives (1.2 mmol) and NaH (0.15 g, 6.4 mmol) were added into this solution and stirredat a room temperature for 0.5-2 h. The mixture was poured into ice water, and then filtered, washedand dried. The compound (4c-t) was isolated and purified by silica gel column chromatography usingCH2Cl2/CH3OH (100:1) as the eluent.

Reference： [1]Molecules,2016,vol. 21

56
[ 124-38-9 ]
[ 2014-83-7 ]
[ 536-74-3 ]
2,6-dichlorobenzyl 3-phenylpropiolate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With caesium carbonate; silver(I) iodide; In acetonitrile; at 40℃; under 760.051 Torr; for 48h;Schlenk technique;	General procedure: In a typical procedure, a 50 mL Schlenk tube was charged withalkyne 1 (1.0 mmol), benzyl halide 2 (1.1 mmol), AgI (0.02 mmol),Cs2CO3 (1.5 mmol) and anhydrous CH3CN (5 mL). CO2 (99.999%,balloon) were then introduced into the reaction mixture understirring. After stirring at 40 C for 48 h, the reaction mixture wascooled to room temperature, ltered and evaporated in vacuo. Theresulting residue was then puried by column chromatography onsilica gel (eluent: petroleum ether: ethyl acetate 20:1) to affordthe corresponding products 3aa-3aq.

Reference： [1]Tetrahedron,2017,vol. 73,p. 900 - 906

57
[ 2014-83-7 ]
[ 10387-40-3 ]
SS-(2,6-dichlorobenzyl)acetyl dithioester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%		Under a nitrogen atmosphere,TolSO2SNa (5 mmol, 1.051 g, 1 equiv.) Was added to the flask,Dichlorobenzyl chloride (6 mmol, 1.173 g, 1.2 equiv.),TBAI (0.25 mmol, 92.4 mg, 5 mol%)And MeCN (20 mL),The reaction system was reacted at 50 for 10 h,Adding silica gel,After removal of the solvent under reduced pressure,Column chromatography to obtain thiosulfonate compound.The resulting thiosulfonate compound (3 mmol, 1 equiv, 1.04 g) was added to the flask,KSAc (3.9 mmol,1.3 equiv, 445 mg)And DCM (20 mL),The reaction system was reacted at room temperature for 6 hours. After the TLC detection reaction was completed, the solvent was removed under reduced pressure,Column chromatography gave product 2i (777 mg, 96%).(Eluent polarity: PE: EA 50: 1).

Reference： [1]Patent: CN106278965,2017,A .Location in patent: Paragraph 0114; 0115; 0116; 0117

58
[ 2014-83-7 ]
[ 1074-82-4 ]
2-(2,6-dichlorobenzyl)isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	In N,N-dimethyl-formamide; at 120℃;Inert atmosphere;	Procedure A: A mixture of appropriate benzyl halide (1 mmol) and potassium phthalimide (1 mmol) in DMF (1.5 mL) was heated at 120 C under nitrogen for 2-3 h. The product was thenprecipitated out by addition of water (5 mL) to the mixture. The solids were filtered and washed with water. The solids were dried under vacuum to give the pure compound. If the product was not pure, it was purified by recrystallization from ethanol; Compound 1 was prepared from 2,6- dichlorobenzyl bromide and potassium phthalimide using general Procedure A. Yield = 67%, offwhite solid. ?H NIVIR (400 MHz, CDC13) 7.84 - 7.77 (m, 2H), 7.74 - 7.66 (m, 2H), 7.33 (d, J=8.0 Hz, 2H), 7.19 (dd, J= 8.5, 7.6 Hz, 1H), 5.14 (s, 2H). ?3C NIVIR (101 1VIHz, CDC13) 167.68 (s), 136.63 (s), 134.16 (s), 131.97 (s), 130.85 (s), 129.74 (s), 128.59 (s), 123.46 (s), 38.38 (s).

Reference： [1]Patent: WO2017/49409,2017,A1 .Location in patent: Page/Page column 213; 214; 215; 216; 217

59
1-(4-chlorophenyl)-2-[(5-[4-(2-methoxyphenyl)piperazin-1-yl]methyl}-4-phenyl-4H-1,2,4-triazol-3-yl)thio]ethanol [ No CAS ]
[ 2014-83-7 ]
1-[5-({2-(4-chlorophenyl)-2-[(2,6-dichlorobenzyl)oxy]ethyl}thio)-4-phenyl-4H-1,2,4-triazol-3-yl]methyl}-4-(2-methoxyphenyl)piperazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%		General procedure: Method 2: NaH (1mmol) was added the solution of the corresponding compound 9 or 12 (1mmol) in THF (10mL) and the mixture was irradiated in monomode microwave reactor in closed vessel with pressure control at 100C and 100W, for 10min. Then, the corresponding substituted benzylchloride (3mmol) was added into it and irradiation was continued for 45minute (for 10a-i) or 50min (for 13a-c) at 125C, 150 Watt. Solvent was evaporated under reduced pressure, and the obtained oily product was extracted with 15mL of ethyl acetate three times in the presence of K2CO3. The organic layer was dried on Na2SO4. After the removal of solvents at a reduced pressure, an oily product formed which was purified by column chromatography (n-hexane/ethyl acetate) on silica gel.

Reference： [1]Chinese Chemical Letters,2017,vol. 28,p. 995 - 1005

60
1-(4-chlorophenyl)-2-[(4-ethyl-5-[4-(2-methoxyphenyl)piperazin-1-yl]methyl}-4H-1,2,4-triazol-3-yl)thio]ethanol [ No CAS ]
[ 2014-83-7 ]
1-[5-({2-(4-chlorophenyl)-2-[(2,6-dichlorobenzyl)oxy]ethyl}thio)-4-ethyl-4H-1,2,4-triazol-3-yl]methyl}-4-(2-methoxyphenyl)piperazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%		General procedure: Method 2: NaH (1mmol) was added the solution of the corresponding compound 9 or 12 (1mmol) in THF (10mL) and the mixture was irradiated in monomode microwave reactor in closed vessel with pressure control at 100C and 100W, for 10min. Then, the corresponding substituted benzylchloride (3mmol) was added into it and irradiation was continued for 45minute (for 10a-i) or 50min (for 13a-c) at 125C, 150 Watt. Solvent was evaporated under reduced pressure, and the obtained oily product was extracted with 15mL of ethyl acetate three times in the presence of K2CO3. The organic layer was dried on Na2SO4. After the removal of solvents at a reduced pressure, an oily product formed which was purified by column chromatography (n-hexane/ethyl acetate) on silica gel.

Reference： [1]Chinese Chemical Letters,2017,vol. 28,p. 995 - 1005

61
2-[(4-benzyl-5-[4-(2-methoxyphenyl)piperazin-1-yl]methyl}-4H-1,2,4-triazol-3-yl)thio]-1-(4-chlorophenyl)ethanol [ No CAS ]
[ 2014-83-7 ]
1-[4-benzyl-5-({2-(4-chlorophenyl)-2-[(2,6-dichlorobenzyl)oxy]ethyl}thio)-4H-1,2,4-triazol-3-yl]methyl}-4-(2-methoxyphenyl)piperazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%		General procedure: Method 2: NaH (1mmol) was added the solution of the corresponding compound 9 or 12 (1mmol) in THF (10mL) and the mixture was irradiated in monomode microwave reactor in closed vessel with pressure control at 100C and 100W, for 10min. Then, the corresponding substituted benzylchloride (3mmol) was added into it and irradiation was continued for 45minute (for 10a-i) or 50min (for 13a-c) at 125C, 150 Watt. Solvent was evaporated under reduced pressure, and the obtained oily product was extracted with 15mL of ethyl acetate three times in the presence of K2CO3. The organic layer was dried on Na2SO4. After the removal of solvents at a reduced pressure, an oily product formed which was purified by column chromatography (n-hexane/ethyl acetate) on silica gel.

Reference： [1]Chinese Chemical Letters,2017,vol. 28,p. 995 - 1005

62
4-benzyl-2-[2-(4-chlorophenyl)-2-hydroxyethyl]-5-[4-(2-methoxyphenyl)piperazin-1-yl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one [ No CAS ]
[ 2014-83-7 ]
4-benzyl-2-{2-(4-chlorophenyl)-2-[(2,6-dichlorobenzyl)oxy]ethyl}-5-[4-(2-methoxyphenyl)piperazin-1-yl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%		General procedure: Method 2: NaH (1mmol) was added the solution of the corresponding compound 9 or 12 (1mmol) in THF (10mL) and the mixture was irradiated in monomode microwave reactor in closed vessel with pressure control at 100C and 100W, for 10min. Then, the corresponding substituted benzylchloride (3mmol) was added into it and irradiation was continued for 45minute (for 10a-i) or 50min (for 13a-c) at 125C, 150 Watt. Solvent was evaporated under reduced pressure, and the obtained oily product was extracted with 15mL of ethyl acetate three times in the presence of K2CO3. The organic layer was dried on Na2SO4. After the removal of solvents at a reduced pressure, an oily product formed which was purified by column chromatography (n-hexane/ethyl acetate) on silica gel.

Reference： [1]Chinese Chemical Letters,2017,vol. 28,p. 995 - 1005

63
[ 2014-83-7 ]
2,6-dichlorobenzyl azide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium azide; In ethanol; water; at 85℃; for 48h;	General procedure: To a solution of 2-methyl benzyl chloride (2.8 g, 20 mmol) in water/EtOH (40mL, 1:1) at room temperature was added NaN3 (3.9 g, 60 mmol). The resulting solution was allowed to stir at 85 C and reflux for 48 h. Afterward, Afterwards, the solution was concentrated in vacuum to remove EtOH, and the aqueous layer was extracted with CH2Cl2 (3 × 10 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to obtain a colorless oil (2.4 g). Then the oil and propiolic amine (0.88 g, 16 mmol) were suspended in a solution of water/t-BuOH (40mL, 1:1), followed by the addition of sodium ascorbate (0.52 g, 3.2 mmol) and CuSO4·5H2O (0.40 g, 1.6 mmol). The resulting reaction was vigorously stirred for 12 h at rt. Afterwards, the solution was concentrated in vacuum to remove t-BuOH, and the aqueous layer was subsequently adjusted to pH = 12, extracted with EtOAc (3 × 20 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to give white solid A1 (2.2 g, 54%). According to the above procedure, corresponding aminomethyl triazoles A2-A15 were prepared in yields ranging from 36% to 62%.
	With sodium azide; at 20℃;	General procedure: To a solution of sodium azide (3.60 g, 55 mmol) in dry dimethyl sulfoxide (120 mL) was added properly substituted benzyl chloride (50 mmol), and the reaction mixture was stirred at room temperature overnight monitored by TLC. Iice-water (100 mL) was carefully added to the reaction mixture and the aqueous layer was extracted with dichlormethane. The combined organic extracts were washed with water (50 mL) and the organic layer was dried over anhydrous sodium sulfate. The drying agent was filtered off and the filtrate was concentrated, leaving compound 1a-1k as a yellow oil (yield: 74%-83%).
	With sodium azide; In ethanol;Reflux;	Add 50 mmol of 2,6-dichlorobenzyl chloride, 0.65 g of NaN3, and 5 mL of absolute ethanol to a 50 mL round-bottomed flask, heat under reflux with stirring, and follow the reaction by TLC; The ethanol was distilled off, and the reaction solution was extracted with EA 2-3 times. The organic layers were combined, and the organic layers were washed 3 times with saturated NaCl solution. After the EA was removed by rotary evaporation, the remaining material was subjected to a silica gel column using petroleum ether as an eluent.

Reference： [1]Journal of Organic Chemistry,2019,vol. 84,p. 6536 - 6545
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 3872 - 3877
[3]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 4871 - 4875
[4]Patent: CN110540526,2019,A .Location in patent: Paragraph 0136-0138

64
[1,2,4]triazolo[3,4-a]phthalazin-6(5H)-one [ No CAS ]
[ 2014-83-7 ]
5-(2,6-dichlorobenzyl)-[1,2,4]triazolo[3,4-a]phthalazin-6(5H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52.6%		General procedure: A mixture of compound 5 (0.5 g, 2.7 mmol) and NaH (0.2g, 8.1 mmol) was dissolved in N,N-dimethylformamide (20ml). The mixture was stirred and refluxed for 30 min. Thereaction was cooled to room temperature, and alkyl bromideor benzyl chloride was added dropwise to the mixture asappropriate before refluxing for 3 h. After the reaction wascompleted, the solvent was removed under reduced pressure.The residue was washed with water (10 ml × 3), filteredoff, and dried and purified using silica gel columnchromatography (CH2Cl2/CH3OH, 60:1) to yield compounds6a-y, a white powder.

Reference： [1]Medicinal Chemistry Research,2017,vol. 26,p. 1935 - 1946

65
7H-[1,2,4]triazolo[4,3-a]perimidine [ No CAS ]
[ 2014-83-7 ]
7-(2,6-dichlorobenzyl)-7H-[1,2,4]triazolo[4,3-a]perimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23.9%	With sodium hydride; In N,N-dimethyl-formamide; at 50℃;	General procedure: The intermediate 4 (0.4 g, 2.0 mmol) was dissolved in anhydrous DMF (5 mL), alkyl bromide, or benzyl chloride derivatives (2.4 mmol) and NaH (0.19 g, 8.0 mmol) were added into this solution and heated at 50 for 2-4 h. The mixture was poured into ice water, and then filtered, washed and dried. The compound (5a-s) was isolated and purified by silica gel column chromatography using CH2Cl2/CH3OH (100:1) as the eluent.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 4409 - 4414

66
1-[2-(4-chlorophenyl)-2-hydroxyethyl]-3-[({3-fluoro-4-[4-(4-fluorophenyl)piperazin-1-yl]phenyl}amino)methyl]-4-phenyl-1H-1,2,4-triazol-5(4H)-one [ No CAS ]
[ 2014-83-7 ]
1-[2-(4-chlorophenyl)-2-(2,6-dichlorobenzyloxy)ethyl]-3-[({3-fluoro-4-[4-(4-fluorophenyl)piperazin-1-yl]phenyl}amino)methyl]-4-phenyl-1H-1,2,4-triazol-5(4H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%		General procedure: Method 1. NaH (10 mmol) was added to the solution of the corresponding compound 15 (10 mmol) in the THF and the mixture was refluxed for 6 h. Then, the corresponding benzyl chloride was added into it and the mixture was refluxed for an additional 14 h. After evaporating the solvent under reduced pressure, an oily mass formed. This was extracted with 15 mL of ethyl acetate three times in the presence of K2CO3 and the organic layer was dried on Na2SO4. After the removal of solvents at a reduced pressure,a solid was obtained, which was recrystallized from acetone. Method 2. The mixture of NaH (1 mmol) and the corresponding compound 15 (1 mmol) in the THF were irradiated in monomode microwave reactor in the closed vessel with pressure control at 80C, 100 Watt for 10 min.Then, suitable benzylchloride (3 mmol) was added and the irradiation was continued for 45 minute at 125C, 150 Watt. After evaporating the solvent under reduced pressure, an oily mass appeared. K2CO3 solution was added into it and extracted with 15 mL of ethyl acetate three times. The combined organic layer was dried on Na2SO4. After the removal of solvents at a reduced pressure, a solid was obtained, which was recrystallized from acetone to give the pure compound.

Reference： [1]Letters in drug design and discovery,2017,vol. 14,p. 1014 - 1034

67
[ 2014-83-7 ]
[ 536-74-3 ]
[ 1237683-39-4 ]

Yield	Reaction Conditions	Operation in experiment
88%	With sodium azide; In water; at 70℃; for 7h;Green chemistry;	General procedure: A mixture of sodium azide (1 mmol), benzyl or alkyl halide (1 mmol), and corresponding acetylene (1 mmolof phenyl acetylene or 2 mmol of alkyl acetylene) and catalyst (5 mg of catalyst equal to 0.1 mol % of copper)was taken in a round bottomed ask containing 1 mL of H 2 O and 0.2 mL of PEG 300 and heated at 70C for3 h under vigorous stirring. After completion of the reaction (monitored by TLC), the catalyst was removedby external magnet, washed with EtOH, and dried under vacuum. The collected solvent was concentratedunder vacuum and the product was allowed to crystalize, which did not require any further purication.The obtained products were conrmed and completely characterized by physical and spectral data (see theSupporting Information).

Reference： [1]Turkish Journal of Chemistry,2017,vol. 41,p. 294 - 307

68
C₂₄H₂₉Cl₂N₅O₂S [ No CAS ]
[ 2014-83-7 ]
1-[(5-[2-[(2,6-dichlorobenzyl)oxy]-2-(2,4-dichlorophenyl)ethyl]thio}-4-ethyl-4H-1,2,4-triazol-3-yl) methyl]-4-(2-methoxyphenyl)piperazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%		General procedure: NaH (10mmol) was added the solution of the corresponding compound 6 or 12a-b (10mmol) in THF and the mixture was sonicated 7-8min. Then, the corresponding substituted benzylchloride (30mmol) was added into it and the reaction was continued for 8min. Solvent was evaporated under reduced pressure, and the obtained oily product was extracted with 15mL of ethyl acetate three times in the presence of K2CO3. The organic layer was dried on Na2SO4. The oily product obtained on the removal of solvent under reduced pressure was purified by column chromatography (n-hexane/ethyl acetate) (3:1) on silica gel.