[ CAS No. 51-36-5 ] {[proInfo.proName]}

Name: 51-36-5|3,5-Dichlorobenzoic acid|97%
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SKU: A197893
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Quality Control of [ 51-36-5 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 51-36-5 ]

Product Details of [ 51-36-5 ]

CAS No. :	51-36-5	MDL No. :	MFCD00002494
Formula :	C₇H₄Cl₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	CXKCZFDUOYMOOP-UHFFFAOYSA-N
M.W :	191.01	Pubchem ID :	5811
Synonyms :

Calculated chemistry of [ 51-36-5 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	43.42
TPSA :	37.3 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.34 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.61
Log Po/w (XLOGP3) :	3.0
Log Po/w (WLOGP) :	2.69
Log Po/w (MLOGP) :	2.79
Log Po/w (SILICOS-IT) :	2.5
Consensus Log Po/w :	2.52

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-3.25
Solubility :	0.107 mg/ml ; 0.00056 mol/l
Class :	Soluble
Log S (Ali) :	-3.45
Solubility :	0.0681 mg/ml ; 0.000357 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.01
Solubility :	0.188 mg/ml ; 0.000986 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.2

Safety of [ 51-36-5 ]

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

Application In Synthesis of [ 51-36-5 ]

* 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 [ 51-36-5 ]
Downstream synthetic route of [ 51-36-5 ]

[ 51-36-5 ] Synthesis Path-Upstream 1~14

1
[ 51-36-5 ]
[ 3290-06-0 ]

Reference： [1] Pest Management Science, 2000, vol. 56, # 10, p. 875 - 881

2
[ 51-36-5 ]
[ 2978-58-7 ]
[ 23950-58-5 ]

Reference： [1] Organic Process Research and Development, 1999, vol. 3, # 3, p. 172 - 176

3
[ 51-36-5 ]
[ 60211-57-6 ]

Reference： [1] Canadian Journal of Chemistry, 1978, vol. 56, p. 1721 - 1723
[2] Synlett, 1997, vol. 1997, # 8, p. 989 - 991
[3] Pest Management Science, 2000, vol. 56, # 10, p. 875 - 881

4
[ 463-73-0 ]
[ 51-36-5 ]
[ 60211-57-6 ]

Reference： [1] Patent: US6255301, 2001, B1,

5
[ 10203-08-4 ]
[ 60211-57-6 ]
[ 51-36-5 ]

Reference： [1] Monatshefte fuer Chemie, 1933, vol. 62, p. 344,347
[2] Monatshefte fuer Chemie, 1933, vol. 62, p. 344,347

6
[ 51-36-5 ]
[ 10203-08-4 ]

Reference： [1] Journal of the Chemical Society [Section] B: Physical Organic, 1966, p. 1011 - 1015

7
[ 51-36-5 ]
[ 917-54-4 ]
[ 14401-72-0 ]
[ 184970-30-7 ]

Reference： [1] Journal of the American Chemical Society, 1983, vol. 105, # 6, p. 1578 - 1584

8
[ 51-36-5 ]
[ 593-74-8 ]
[ 56961-33-2 ]

Reference： [1] Patent: CN105859574, 2016, A, . Location in patent: Paragraph 0007

9
[ 51-36-5 ]
[ 124-41-4 ]
[ 82477-67-6 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 22, p. 6419 - 6423
[2] Medicinal Chemistry Research, 2017, vol. 26, # 9, p. 2161 - 2171
[3] European Journal of Medicinal Chemistry, 2018, vol. 156, p. 230 - 239
[4] Heterocycles, 1985, vol. 23, # 6, p. 1483 - 1491
[5] Patent: WO2007/39736, 2007, A1, . Location in patent: Page/Page column 40
[6] Patent: US2008/293775, 2008, A1, . Location in patent: Page/Page column 23
[7] Chemical Biology and Drug Design, 2013, vol. 82, # 3, p. 336 - 347

10
[ 51-36-5 ]
[ 82477-67-6 ]

Reference： [1] Patent: US2008/293775, 2008, A1, . Location in patent: Page/Page column 25

11
[ 67-56-1 ]
[ 51-36-5 ]
[ 82477-67-6 ]

Reference： [1] Archiv der Pharmazie, 2011, vol. 344, # 3, p. 197 - 204

12
[ 51-36-5 ]
[ 20776-67-4 ]

Reference： [1] Patent: CN105859574, 2016, A,

13
[ 51-36-5 ]
[ 890707-28-5 ]

Reference： [1] Patent: CN105859574, 2016, A,

14
[ 51-36-5 ]
[ 68-12-2 ]
[ 153203-80-6 ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 2 h; Stage #2: at 20℃;	The reaction kettle is added compound XVI (190g, 1.0 µM), anhydrous THF (1L) dissolved, cooling to -78 °C, slowly adds by drops positively BuLi (2.5M, 0 . 5L), to maintain the temperature of the reaction 2 hours after DMF slowly adds by drops anhydrously (95g, 1.3 µM), the reaction temperature to room temperature slowly to the disappearance of the raw material, to join the semi-saturated ammonium chloride quenching, ethyl acetate after extracting the concentrated white solid, petroleum ether ethyl acetate system beating shall be required compound XII (179g, 82percent).
80%	Stage #1: With lithium diisopropyl amide In tetrahydrofuran at -78℃; Inert atmosphere Stage #2: for 2 h;	Take 3,5-dichlorobenzoic acid (191mg, 1mmol) was dissolved in 5mL of anhydrous tetrahydrofuran, and argon protection, followed by cooling to -78 .At this temperature, slowly added dropwise 2N lithium diisopropylamide (LDA) in tetrahydrofuran (0.6 mL, 1.2mmol).Stirring was continued for 0.5 ~ 1h after addition was complete.It was then slowly added dropwise a solution of 0.5mL DMF 2mL of tetrahydrofuran, was added after the reaction was continued for 2h, TLC detection, reaction was almost completed. The residue was quenched with 1N dilute hydrochloric acid and evaporated to dryness. The residue was purified by column chromatography using ethyl acetate and water and the ethyl ester layer to give the title compound 3,5-dichloro-4-formylbenzoic acid (175 mg , 80percent).

Reference： [1] Patent: CN106565625, 2017, A, . Location in patent: Paragraph 0073-0074
[2] Patent: CN104341316, 2017, B, . Location in patent: Paragraph 0379; 0381; 0382

[ 51-36-5 ] Synthesis Path-Downstream 1~85

1
[ 186581-53-3 ]
[ 51-36-5 ]
[ 2905-67-1 ]

Reference： [1]Chemische Berichte,1941,vol. 74,p. 807,821

2
[ 10203-08-4 ]
[ 60211-57-6 ]
[ 51-36-5 ]

Reference： [1]Monatshefte fur Chemie,1933,vol. 62,p. 344,347
[2]Monatshefte fur Chemie,1933,vol. 62,p. 344,347

3
[ 51-36-5 ]
[ 2905-62-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	With thionyl chloride; for 5h;Reflux;	<strong>[51-36-5]3,5-Dichlorobenzoic acid</strong> 2a (5.0 g, 26.2 mmol) was dissolved in 50 mL of thionyl chloride and refluxed for 5 hours. Concentration under reduced pressure and removal of thionyl chloride afforded crude 3,5-dichlorobenzoyl chloride 12a (5.5 g, yellow oil). Yield: 100%.
100%	With thionyl chloride; N,N-dimethyl-formamide; In toluene; for 3h;Reflux;	10.0 g (0.0524 mole, 1.0 eq.) of <strong>[51-36-5]3,5-dichlorobenzoic acid</strong> was suspended in 300 ml of toluene. 10.0 ml (0.136 mole, 2.6 eq.) SOCI2 and 1.0 ml (catalytic amount) of DMF were added to the suspension and heated to reflux for 3 hours. The toluene was distilled of by a vacuum distillation to give dark brown oil. The yield was 100% and compound B was used without further purification.
	With thionyl chloride; for 6h;Heating / reflux;	Example 6: N-(3,5-Dichlorophenyl)-4-methylpiperazine-1-carboxyamide; <strong>[51-36-5]3,5-Dichlorobenzoic acid</strong> (3.82 g, 20 mmol) was added with thionyl chloride (24.48 g, 205 mmol), and the mixture was refluxed for 6 hours. After completion of the reaction, excess thionyl chloride was evaporated, and the residue was dried overnight in a desiccator. The resulting acid chloride was used for the subsequent reaction as it was. A suspension of sodium azide (1.78 g, 35.6 mmol) in acetone (15 ml) was added dropwise with a solution of 3,5-dichlorobenzoyl chloride (3.87 g, 18.48 mmol) in acetone (15 ml) with stirring under ice cooling, and the mixture was stirred with ice cooling for 1 hour. The reaction mixture was added with water, and the deposited crystals were collected by filtration and dried under reduced pressure to obtain an acid azide compound. A solution of the resulting 3,5-dichlorobenzoyl azide (0.54 g, 2.5 mmol) in toluene (5 ml) was heated at 60 to 70C until generation of nitrogen ceased. After effervescence ceased, the mixture was added with a solution of 1-methylpiperazine (0.275 g, 2.75 mmol) in toluene (3 ml), and the mixture was stirred for 5 minutes. The reaction mixture was added with water, and the aqueous layer was made sufficiently acidic with 10% hydrochloric acid and washed with dichloromethane. Then, the aqueous layer was made sufficiently basic with 20% aqueous potassium carbonate and extracted with dichloromethane. The organic layer was washed with a small volume of water and dried over anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure. The resulting mixture was recrystallized from ether/n-hexane for purification to obtain colorless prism crystals. Melting point: 184-185C. 1H-NMR (CDCl3): 2.32 (3H, s), 2.43 (4H, t, J = 5 Hz), 3.50 (4H, t, J = 5 Hz), 6.50 (1H, brs), 7.00 (1H, s), 7.31-7.32 (2H, s).

	With thionyl chloride;Reflux;	General procedure: The selected acid was refluxed in thionyl chloride for 2-3 h, and then the solution was cooled to room temperature, and the remaining thionyl chloride was evaporated to afford the acyl chloride, which was used without further purification.
	With thionyl chloride;Reflux;	Compound 9a (191 mg, 1 mmol) was refluxed in excess of thionylchloride (3 mL) overnight. Excess of thionyl chloride was evaporatedand the residue was dissolved in CH2Cl2, 3-bromopropylamine hydrobromide (328 mg, 1.5 mmol was addedfollowed by triethylamine (TEA; 0.42 mL, 3 mmol). The reactionmixture was stirred at room temperature. After the reaction wascompleted, the reaction mixture was diluted with CH2Cl2 andsequentially washed with water, 1 N HCl and saturated NaHCO3.The organic layer was dried over MgSO4, filtered and concentrated.The obtained product was purified by column chromatographywith n-hexane/ethyl acetate (EtOAc) = 4:1 to obtain 10a, (236 mg,76%) as white solid.
	With thionyl chloride; at 80℃; for 18h;Inert atmosphere;	General procedure: A solution of 3,5-dimethylbenzoic acid (300 mg, 2.00 mmol) in thionyl chloride (1.2 mL, 16 mmol) was heated to reflux and allowed to react for 18 h, after which the reaction mixture was cooled and the thionyl chloride was removed under vacuum with the assistance of excess toluene as an azeotrope. Crude acid chloride (30) was taken to the next step without further purification.
	With thionyl chloride;Reflux;	Compound 9a (191 mg, 1 mmol) was mixed overnight with excess thionyl chloride (3 mL).The excess thionyl chloride was evaporated and the residue was dissolved in CH2Cl2 and 3-bromopropylamine hydrobromide (328 mg, 1.5 mmol) followed by triethylamine (TEA; 0.42 mL, , 3 mmol). The reaction mixture was stirred at room temperature, and after the reaction was complete, the reaction mixture was diluted with CH2Cl2, washed successively with 1N HCl, saturated NaHCO3 and water. The organic layer was dried over MgSO4, filtered and concentrated. To obtain the white solid 10a (236 mg, 76%), the obtained product was purified by column chromatography using n-hexane and ethyl acetate (EtOAc) as a 4: 1 mixture.
	With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 0 - 20℃; for 6h;Inert atmosphere;	General procedure: To a stirred solution of 200 mg acid in 5 cm3, drydichloromethane oxalyl chloride (1.5 equiv.) was addeddropwise under nitrogen atmosphere at 0 C during which the colour of the solution changes to black. After 6 h,solvent was removed under reduced pressure and the soformedacid chloride was used for the next reaction withoutfurther purification.
	With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 0 - 20℃; for 12h;	General procedure: To a solution of aroyl acid (1.0eq) in CH2Cl2 was added oxalyl dichloride (1.1eq) and DMF (2-5 drops) at 0C. The mixture was allowed to stir at room temperature for 2-12h. Then the mixture was concentrated to give compounds 1, 18-24. The products were used directly in the next reaction.
	With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 0 - 20℃; for 3h;	General procedure: To a 100 mL three-necked flask, acid (20 mmol), DMF (3 drops), and anhydrous CH2Cl2 (30 mL)were added. Oxalyl chloride (40 mmol, 2 equiv) was added dropwise at 0C resulting in vigorousbubbling. The mixture was stirred for 3 h at room temperature, and the solvent was then removedin vacuo. The resulting acid chloride was used immediately without further purification. The acidcholoride was then re-dissolved in 25 mL dry CH2Cl2 and added dropwise to a 30 mL dry CH2Cl2solution containing amine (24 mmol) and Et3N (30 mmol) at 0 C. After stirring for 6h at roomtemperature, the resulting mixture was washed with brine, dried over Na2SO4, filtered andconcentrated under reduced pressure. The residue was purified by flash chromatography to give thedesired product.
	With thionyl chloride;Reflux;	Compound 28a (191 mg, 1 mmol) was refluxed in excess of thionylchloride (3 mL) overnight. Excess of thionyl chloride was evaporatedand the residue was dissolved in CH2Cl2, 3-bromopropylamine hydrobromide(328 mg, 1.5 mmol was added followed by triethylamine (TEA;0.42 mL, 3 mmol). The reaction mixture was stirred at room temperature.After the reaction was completed, the reaction mixture was dilutedwith CH2Cl2 and sequentially washed with water, 1 N HCl and saturatedNaHCO3. The organic layer was dried over MgSO4, filtered and concentrated.The obtained product was purified by column chromatographywith n-hexane: Ethyl acetate (EtOAc)=4:1 to obtain 29a,(236 mg, 76%) as white solid.
	With thionyl chloride; for 2h;Reflux;	General procedure: A solution of 24 (1.0 equiv.) in SOCl2 (40.5 equiv.) was heated under reflux for 2 hours. After cooling, the reaction mixture was concentrated under vacuum. Crude residue was diluted in DCM and cooled at 0C. The appropriate amine (1.2 equiv.) and Et3N (2.0 equiv.) were added and the resulting mixture was stirred at rt overnight. The solution was washed successively with a solution of HCl 2N, a saturated solution of NaHCO3 and brine, dried over Na2SO4 and concentrated under vacuum. The resulting solid was then purified by column chromatography on silica gel using the appropriate heptanes:EtOAc mixture.
	With thionyl chloride; N,N-dimethyl-formamide; for 2h;Reflux;	A mixture of <strong>[51-36-5]3,5-dichlorobenzoic acid</strong> (5.0 g, 26 mmol) and thionyl chloride (8.2 g, 68 mmol) was heated at reflux for2 hours. The reaction was monitored by TLC (methanol/ethyl acetate: v/v = 1/4). After the reaction completed, the mixture was cooled to room temperature and concentratedunder reduced pressure to obtain 3,5-dichlorobenzoyl chloride (3), which may be used directly in the synthesis of the following amide derivatives.

Reference： [1]Patent: CN109574927,2019,A .Location in patent: Paragraph 0439; 0441-0444
[2]Patent: WO2019/175263,2019,A1 .Location in patent: Page/Page column 21
[3]Journal of Medicinal Chemistry,1975,vol. 18,p. 177 - 182
[4]Journal of the Chemical Society,1903,vol. 83,p. 1213
[5]Journal of Medicinal Chemistry,1991,vol. 34,p. 752 - 757
[6]European Journal of Medicinal Chemistry,1996,vol. 31,p. 331 - 334
[7]Journal of Medicinal Chemistry,1998,vol. 41,p. 1688 - 1695
[8]Pesticide Science,1994,vol. 41,p. 139 - 148
[9]Bioorganic and Medicinal Chemistry Letters,2000,vol. 10,p. 1723 - 1727
[10]Bioorganic and Medicinal Chemistry,2004,vol. 12,p. 2335 - 2341
[11]Patent: WO2005/105759,2005,A1 .Location in patent: Page/Page column 81-82
[12]Patent: EP1798227,2007,A1 .Location in patent: Page/Page column 12-13
[13]Molecules,2009,vol. 14,p. 3313 - 3338
[14]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 4273 - 4278
[15]European Journal of Medicinal Chemistry,2011,vol. 46,p. 3526 - 3530
[16]Journal of Medicinal Chemistry,2011,vol. 54,p. 5403 - 5413
[17]Chinese Chemical Letters,2012,vol. 23,p. 1233 - 1236,4
[18]Journal of the American Chemical Society,2013,vol. 135,p. 4628 - 4631
[19]MedChemComm,2013,vol. 4,p. 1443 - 1451
[20]Journal of Medicinal Chemistry,2015,vol. 58,p. 4573 - 4580
[21]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 6418 - 6426
[22]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 3700 - 3704
[23]Macromolecules,2016,vol. 49,p. 4480 - 4489
[24]Patent: KR101784964,2017,B1 .Location in patent: Paragraph 0139-0143
[25]Monatshefte fur Chemie,2018,vol. 149,p. 1093 - 1100
[26]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 3321 - 3344
[27]Synlett,2018,vol. 29,p. 1451 - 1454
[28]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 4127 - 4135
[29]European Journal of Medicinal Chemistry,2019,vol. 177,p. 269 - 290
[30]Journal of Chemical Crystallography,2020
[31]Bioorganic and medicinal chemistry letters,2012,vol. 22,p. 6974 - 6979,6

4
[ 51-36-5 ]
[ 23082-45-3 ]

Yield	Reaction Conditions	Operation in experiment
95.3%	With sulfuric acid; nitric acid; at 20℃; for 2.5h;	Reference Example 1Production of 3,5-dichloro-2-nitrobenzoic acidInto a 500-ml, four-necked flask equipped with a mechanical stirrer, a dropping funnel and a thermometer were added 490 g (5 mol) of concentrated sulfuric acid and 95.5 g (0.5 mol) of <strong>[51-36-5]3,5-dichlorobenzoic acid</strong>. Thereto was added dropwise 37.8 g (d=1.52, 0.6 mol) of concentrated nitric acid with the temperature of the system being controlled to be 20 C. or lower. Then, stirring was conducted at room temperature for 2.5 hours. The reaction mixture was poured into 1,000 g of ice, followed by stirring and filtration. The crystal obtained was washed with 2 liters of water and dried to obtain 3,5-dichloro-2-nitrobenzoic acid as 112.4 g of a white crystal. HPLC purity=96.8% Yield=95.3%1H NMR (300 MHz, CDCl3) 6 value:8.02 (d, J=2.1 Hz, 1H), 7.76 (d, J=2.1 Hz, 1H) ppmGC-MS M+=235
94%	With Concentrated HNO3; In sulfuric acid; water;	Step 1. To a solution of <strong>[51-36-5]3,5-dichlorobenzoic acid</strong> (25 g, 1 equiv) in 125 mL of concentrated sulfuric acid at 0 C. was added concentrated HNO3 (70% in H2O, 11.9 g, 1.1 equiv) dropwise. The mixture was stirred at 0 C. to rt overnight, and then poured into ice-water. The suspension was then filtered and the solid was washed with cold water and dried to give 2-nitro-<strong>[51-36-5]3,5-dichlorobenzoic acid</strong> (28 g, 94%). MS found for C7H2Cl2NO4 (M-H)-: 226.
	With nitric acid; In dichloroacid;	Step 1: 3,5-dichloro-2-nitrobenzoic acid In a 5-liter, 3-necked flask were placed 2000 ml. of 90% nitric acid. The mixture was stirred and heated to 70 C. The heating mantel was removed and, with continued stirring, 500 g. of solid <strong>[51-36-5]3,5-dichlorobenzoic acid</strong> was added in portions so as to maintain a reaction temperature of about 70 C. (The addition is only very mildly exothermic so that large portions of the dichloroacid may be added at one time. The total time for addition of the 500 g. was about 20 min.) After the addition, the reaction was stirred and heated at 75-80 C. for 3 hr. The mixture (containing some solid) was then cooled, finally in ice. The solid was collected on a sintered glass funnel and washed with cold water (3*500 ml.) and dried. Yield 555.3 g. (90%); m.p. 190-192 C.

With sulfuric acid; nitric acid; at 0 - 20℃;

Step 1To a solution of <strong>[51-36-5]3,5-dichloro-benzoic acid</strong> (25 g, 0.13 mol) in 125 mL of concentrated H2SO4 at 0 C was added HNO3 (68%) dropwise. The mixture was stirred at 0 0C and allowed to warm to rt overnight. The mixture was poured into ice-water. The suspension was then filtered and the solid was washed with cold water and dried to give the crude product (30 g, 98%). 1H NMR (d6-DMSO): 8.01 (s, IH), 8.28 (s, IH).

Reference： [1]Patent: US2012/178931,2012,A1 .Location in patent: Page/Page column 10
[2]Patent: US2004/77690,2004,A1
[3]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 2179 - 2185
[4]Monatshefte fur Chemie,1933,vol. 63,p. 385,390
[5]Patent: US4218368,1980,A
[6]Patent: WO2009/108332,2009,A1 .Location in patent: Page/Page column 54

5
[ 6575-00-4 ]
[ 51-36-5 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1892,vol. 269,p. 231

6
[ 25186-47-4 ]
[ 51-36-5 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1885,vol. 231,p. 317
[2]Journal of the American Chemical Society,1951,vol. 73,p. 455

7
[ 56961-25-2 ]
[ 51-36-5 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1923,vol. 42,p. 151,153,164,168
Recueil des Travaux Chimiques des Pays-Bas,1924,vol. 43,p. 867
[2]Il Farmaco,1990,vol. 45,p. 617 - 630

8
[ 56961-25-2 ]
[ 51-36-5 ]
[ 618-62-2 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1923,vol. 42,p. 151,153,164,168
Recueil des Travaux Chimiques des Pays-Bas,1924,vol. 43,p. 867

9
[ 51-36-5 ]
[ 917-54-4 ]
[ 14401-72-0 ]
[ 184970-30-7 ]

Reference： [1]Journal of the American Chemical Society,1983,vol. 105,p. 1578 - 1584

10
[ 51-36-5 ]
[ 124-41-4 ]
[ 82477-67-6 ]

Yield	Reaction Conditions	Operation in experiment
80%	With N,N,N,N,N,N-hexamethylphosphoric triamide; In methanol; at 115 - 120℃; for 15h;	A mixture of 3,5-dichlorobenzoic acid (3, 2.0 g, 10.4 mmol) and NaOMe (6.74 mL, 25 wt % solution in methanol, 31.2 mmol) in HMPA (40 mL) was heated at 120C for 15 h. The mixture was poured into ice-water and acidified with conc. HCl to give 3-chloro-5-methoxybenzoic acid (4, 1.56 g, 80%) as a precipitate which was collected by filtration and used in the next step without purification. 1H NMR (300 MHz, DMSO-d6) delta 3.82 (s, 3H), 7.30 (t, 1H, J = 2.0 Hz), 7.38 (q, 1H, J = 1.3 Hz), 7.47 (t, 1H, J = 1.6 Hz).
	With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; at 170℃; for 120h;	(i) S-chloro-theta-methoxybenzoic acidSodium methoxide (25% wt, 7 ml) was added to a stirred solution of 3,5-dichlorobenzoic acid (2 g) in DMPU (10 ml) and heated at 170 C for 5 days. The reaction was poured onto IM HCl (50 ml). The resulting solid formed was filtered and washed with water, then dried in vacuo to give the subtitle compound (0.8 g). 1H NMR DMSO-d6: delta 13.34 (IH, s), 7.46 (IH, s), 7.38 (IH, s), 7.3 (IH, s), 3.77 (3H, s).(H)
		(i) 3-chloro-5-methoxybenzoic acid Sodium methoxide (25% wt., 7 ml) was added to a stirred solution of 3,5-dichlorobenzoic acid (2 g) in DMPU (10 ml) and heated at 170 C. for 5 days. The reaction was poured onto 1M HCl (50 ml). The resulting solid formed was filtered and washed with water, then dried in vacuo to give the subtitle compound (0.8 g). 1H NMR DMSO-d6: delta 13.34 (1H, s), 7.46 (1H, s), 7.38 (1H, s), 7.3 (1H, s), 3.77 (3H, s).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 6419 - 6423
[2]Bioorganic and Medicinal Chemistry,2019,vol. 27,p. 655 - 663
[3]Medicinal Chemistry Research,2017,vol. 26,p. 2161 - 2171
[4]European Journal of Medicinal Chemistry,2018,vol. 156,p. 230 - 239
[5]Heterocycles,1985,vol. 23,p. 1483 - 1491
[6]Patent: WO2007/39736,2007,A1 .Location in patent: Page/Page column 40
[7]Patent: US2008/293775,2008,A1 .Location in patent: Page/Page column 23
[8]Chemical Biology and Drug Design,2013,vol. 82,p. 336 - 347

11
[ 51-36-5 ]
[ 60211-57-6 ]

Yield	Reaction Conditions	Operation in experiment
86.9%	With borane-THF; In tetrahydrofuran; at 0 - 20℃; for 2h;	3,5-Dichlorobenzoic acid 2a (5.0 g, 26.32 mmol) was dissolved in 50 mL of tetrahydrofuran, and a borane tetrahydrofuran solution (52.6 mL, 52.64 mmol, 1 M/THF) was added dropwise at 0 C, and the mixture was reacted at room temperature for 2 hours. At 0 C, 50 mL of 10% sodium hydroxide solution was added to quench the reaction. The organic layer was washed with a saturated sodium chloride solution (50 mL). Methanol 6a (4.0 g, white solid), yield: 86.9%

Reference： [1]Patent: CN109574927,2019,A .Location in patent: Paragraph 0329; 0331-0335
[2]Canadian Journal of Chemistry,1978,vol. 56,p. 1721 - 1723
[3]Synlett,1997,vol. 1997,p. 989 - 991
[4]Pest Management Science,2000,vol. 56,p. 875 - 881

12
[ 51-36-5 ]
[ 17287-03-5 ]
[ 2905-67-1 ]

Reference： [1]Chemosphere,1997,vol. 35,p. 1233 - 1241

13
[ 25186-47-4 ]
[ 7697-37-2 ]
[ 51-36-5 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1885,vol. 231,p. 317

14
[ 14401-72-0 ]
aqueous KOH-solution [ No CAS ]
[ 51-36-5 ]

Reference： [1]Chemische Berichte,1937,vol. 70,p. 916,923

15
[ 56961-85-4 ]
[ 7732-18-5 ]
Ca(OH)2 [ No CAS ]
[ 60211-57-6 ]
[ 51-36-5 ]

Reference： [1]Monatshefte fur Chemie,1933,vol. 62,p. 344,347

16
[ 51-36-5 ]
[ 7697-37-2 ]
[ 23082-45-3 ]

Yield	Reaction Conditions	Operation in experiment
	at 70 - 80℃;

Reference： [1]Asinger [Monatshefte fur Chemie, 1933, vol. 63, p. 385,390]

17
[ 56961-25-2 ]
[ 7697-37-2 ]
K₂S₂O₅ [ No CAS ]
[ 51-36-5 ]
[ 618-62-2 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1923,vol. 42,p. 151,153,164,168
Recueil des Travaux Chimiques des Pays-Bas,1924,vol. 43,p. 867

18
[ 620611-27-0 ]
[ 51-36-5 ]
[ 918431-94-4 ]

Yield	Reaction Conditions	Operation in experiment
		fe/Y-butyl 4-((3 ,5-dichlorobenzamido)methyl)-4-fluoropiperidine- 1 -carboxylate (4-5); 1-Hydroxybenzotriazole (6.27 g, 46.4 mmol) and 3,5-dichlorobenzoic acid (8.13 g, 42.6 mmol) were suspended in 210 mL dry CH2Cl2. Diisopropylethylamine (13.5 mL, 77.4 mmol) was added and all compounds went into solution. Amine 4-4 (10.4 g crude, 38.7 mmol) was added in 210 mL dry CH2CI2. PS-carbodiimide resin (59.5 g, 77.4 mmol) was then added and the mixture was stirred for 14 h. MP-carbonate resin (41.8 g, 120 mmol) was added and stirring was resumed for 3 h. The reaction was then filtered to remove resin and concentrated in vacuo, yielding 22.2 g of crude 4-5 as a viscous yellow oil. The crude amide 4-5 was carried forward. 1HNMR (CDCl3, 300 MHz): 7.94 (d, J= 1.8 Hz, IH),7.66 (d, J= 1.8 Hz, 2H), 6.44 (br t, IH)5 3.93 (br, 2H), 3.65 (br, 2H), 3.12 (br t, 2H), 1.83 (br t, 2H), 1.67 (m, 2H), 1.46 (s, 9H); MS (Electrospray): m/z 427.1 (M+Na), 349.1 (M-t-Bu+H).

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 3692 - 3695
[2]Patent: WO2007/2884,2007,A2 .Location in patent: Page/Page column 26

19
[ 51-36-5 ]
[ 3290-06-0 ]

Yield	Reaction Conditions	Operation in experiment
98.8%		The method for synthesizing 3,5-dichlorobenzyl chloride includes the following steps:1) Under a argon atmosphere, add 1 mol of 3,5-dichlorobenzoic acid, anhydrous THF and sodium borohydride to the reaction vessel.The temperature was raised to 60 C for 12 min, potassium chloride, polyethylene glycol 200 and sodium hydroxide aqueous solution of pH=14 were added to start ultrasonic assist, and the ultrasonic power and frequency were 420 W and 60 KHz, respectively.The control temperature is 110 C, the reaction pressure is maintained at 2 atmospheres, and the reaction is completed for 4 hours;The ratio of 3,5-dichlorobenzoic acid to sodium borohydride and potassium chloride is 1:0.42:1.4; 3,5-dichlorobenzoic acid and anhydrous THF,The amount ratio of the aqueous sodium hydroxide solution was 1 mmol: 2 ml: 0.8 ml.2) After cooling the system, about 2 times the volume of the reaction solution of ethyl acetate is added, the insoluble matter is removed by filtration, and the layers are separated. The organic phase is dried over anhydrous magnesium sulfate and concentrated.Recrystallization gave the product in a molar yield of 98.8% and HPLC purity 98.1%.

Reference： [1]Patent: CN109232164,2019,A .Location in patent: Paragraph 0008; 0026-0048
[2]Pest Management Science,2000,vol. 56,p. 875 - 881
[3]Patent: CN109574927,2019,A

20
[ 51-36-5 ]
[ 96826-41-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: hexamethylphosphoramide / 15 h / 115 - 120 °C 2: 70 percent / acetyl chloride / 15 h / Ambient temperature
	Multi-step reaction with 2 steps 1: N,N,N,N,N,N-hexamethylphosphoric triamide; sodium methylate / 15 h / Heating 2: acetyl chloride / 0 - 20 °C
	Multi-step reaction with 2 steps 1: N,N,N,N,N,N-hexamethylphosphoric triamide / 15 h / 115 - 120 °C 2: acetyl chloride / 15 h / 0 - 20 °C

	Multi-step reaction with 2 steps 1: N,N,N,N,N,N-hexamethylphosphoric triamide / 15 h / 115 - 120 °C 2: acetyl chloride / 15 h / 20 °C
	Multi-step reaction with 2 steps 1: N,N,N,N,N,N-hexamethylphosphoric triamide / 15 h / 115 - 120 °C 2: acetyl chloride / 15 h / 20 °C
	Multi-step reaction with 2 steps 1: N,N,N,N,N,N-hexamethylphosphoric triamide / methanol / 15 h / 115 - 120 °C 2: methanol / 15 h / 0 - 20 °C

Reference： [1]Takahashi, Kimio; Shimizu, Sumio; Ogata, Masaru [Heterocycles, 1985, vol. 23, # 6, p. 1483 - 1491]
[2]El-Gamal, Mohammed I.; Sim, Tae Bo; Hong, Jun Hee; Cho, Jung-Hyuck; Yoo, Kyung Ho; Oh, Chang-Hyun [Archiv der Pharmazie, 2011, vol. 344, # 3, p. 197 - 204]
[3]El-Gamal, Mohammed I.; Choi, Hong Seok; Yoo, Kyung Ho; Baek, Daejin; Oh, Chang-Hyun [Chemical Biology and Drug Design, 2013, vol. 82, # 3, p. 336 - 347]
[4]Park, Byung-Jun; El-Gamal, Mohammed I.; Lee, Woo-Suck; Shin, Ji-Sun; Yoo, Kyung Ho; Lee, Kyung-Tae; Oh, Chang-Hyun [Medicinal Chemistry Research, 2017, vol. 26, # 9, p. 2161 - 2171]
[5]El-Gamal, Mohammed I.; Park, Byung-Jun; Oh, Chang-Hyun [European Journal of Medicinal Chemistry, 2018, vol. 156, p. 230 - 239]
[6]Tarazi, Hamadeh; El-Gamal, Mohammed I.; Oh, Chang-Hyun [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 4, p. 655 - 663]

21
[ 51-36-5 ]
[ 98406-04-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: hexamethylphosphoramide / 15 h / 115 - 120 °C 2: 70 percent / acetyl chloride / 15 h / Ambient temperature 3: 93 percent / BBr₃ / CH₂Cl₂ / 3 h / 0 °C

Reference： [1]Takahashi, Kimio; Shimizu, Sumio; Ogata, Masaru [Heterocycles, 1985, vol. 23, # 6, p. 1483 - 1491]

22
[ 51-36-5 ]
[ 2905-67-1 ]

Reference： [1]Journal of the American Chemical Society,1951,vol. 73,p. 455

23
[ 56461-98-4 ]
[ 51-36-5 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1885,vol. 231,p. 317

24
[ 51-36-5 ]
[ 18107-18-1 ]
[ 2905-67-1 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; diethyl ether; dichloromethane; for 0.166667h;	Trimethylsilyldiazomethane (2M/ether, 3.5 mL) was added slowly to a solution of 3,5- dichlorobenzoic acid (2-C) (955 mg, 5.0 mmol) in methylene chloride (5.0 mL) and methanol (2.0 mL) until the yellow color persisted. After stirring for 10 min, the mixture was evaporated in vacuo to give methyl 3,5-dichlorobenzoate (2-D).

Reference： [1]Patent: WO2005/97759,2005,A1 .Location in patent: Page/Page column 34-35

25
[ 7758-99-8 ]
[ 2789-92-6 ]
[ 51-36-5 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; urea; sodium nitrite; In methanol; water;	EXAMPLE 1 206 parts of <strong>[2789-92-6]2-amino-3,5-dichlorobenzoic acid</strong> is introduced into 1000 parts of water, then 180 parts of 50% by weight caustic soda solution and 70 parts of sodium nitrite are added and the mixture is allowed to flow while cooling into a mixture of 200 parts of water and 600 parts of concentrated hydrochloric acid (25% by weight strength). The mixture is stirred for another hour, 20 parts of urea is added and the whole is allowed to flow at 65C with vigorous evolution of nitrogen into a mixture of 70 parts of methanol, 400 parts of water and 3 parts of copper(II) sulfate. The mixture is stirred for another 25 minutes, cooled to ambient temperature and suction filtered. 183 parts (96% of theory) of 3,5-dichlorobenzoic acid is obtained having a melting point of 179 to 181C.
	With hydrogenchloride; urea; sodium nitrite; In ethanol; water;	EXAMPLE 4 144 parts of 50% by weight caustic soda solution and 80 parts of ethanol are added to a mixture of 165 parts of <strong>[2789-92-6]3,5-dichloroanthranilic acid</strong> and 1400 parts of water. 56 parts of sodium nitrite is added to the clear solution and the mixture is cooled to 10 to 15C. Diazotization is carried out by slowly adding 400 parts of concentrated hydrochloric acid. The mixture is stirred for another hour, 16 parts of urea and 2 parts of copper(II) sulfate are added and the mixture is allowed to flow within 15 minutes into 200 parts of water at 70C. Thirty minutes later the whole is cooled to ambient temperature and the end product is isolated by suction filtration. The yield is 148 parts (97% of theory) of 3,5-dichlorobenzoic acid having a melting point of 178 to 180C.

Reference： [1]Patent: US3931300,1976,A
[2]Patent: US3931300,1976,A

26
[ 2789-92-6 ]
[ 51-36-5 ]

Yield	Reaction Conditions	Operation in experiment
64%	With tetrahydrofuran; tert.-butylnitrite; dimethyl sulfoxide; at 30℃; for 1h;Green chemistry;	General procedure: A solution of amine 2 (5 mmol) in THF (3 mL) was added dropwise over 20 min to a solution of t-BuONO (7.5 mmol) and DMSO (0.5 mmol) in THF (7 mL) at 30 C. The mixture was stirred at 30 C until the starting materials 2 were consumed (monitored by TLC). The solvent was evaporated, and the yields of the low boiling point products were determined by GC; the high boiling point products were isolated by column chromatography on silica gel (hexane/ethyl acetate).
	In ethanol;	EXAMPLE 5 200 parts of ethanol is slowly added to a solution, heated to 70C, of the diazonium salt prepared as described in Example 1 from 412 parts of <strong>[2789-92-6]3,5-dichloroanthranilic acid</strong>; elimination of nitrogen immediately takes place with evolution of heat. The mixture is stirred for another 15 minutes and 350 parts (92% of theory) of 3,5-dichlorobenzoic acid having a melting point of 176 to 178C is isolated as described in Example 1.
	With sodium nitrite; In water; isopropyl alcohol;	EXAMPLE 6 206 parts of <strong>[2789-92-6]3,5-dichloroanthranilic acid</strong> are introduced into 500 parts of 45 percent strength by weight sulfuric acid and 400 parts of isopropanol. A solution of 100 parts of sodium nitrite in 140 parts of water is run in over 5 hours at 80 C.; nitrogen is evolved. The mixture is cooled, 1,000 parts of water are added and the product is filtered off. 172 parts (90% of theory) of 3,5-dichlorobenzoic acid of melting point 175-178 C. are obtained.

	With hydrogenchloride; sodium nitrite; In ethanol; water;	EXAMPLE 9 206 parts of <strong>[2789-92-6]3,5-dichloroanthranilic acid</strong> are introduced into 400 parts of ethanol and 400 parts of 36 percent strength by weight hydrochloric acid are then added. A solution of 100 parts of NaNO2 in 150 parts of water is run in at 75 C., resulting in the evolution of nitrogen. The mixture is stirred for one hour at 75 C. and is then cooled, 1,500 parts of water are added and the product is filtered off. 183 parts (89% of theory) of 3,5-dichlorobenzoic acid of melting point 170-175 C. are obtained.
	With sodium nitrite; In water; isopropyl alcohol;	EXAMPLE 8 206 parts of <strong>[2789-92-6]3,5-dichloroanthranilic acid</strong> are introduced into 200 parts of isopropanol and 800 parts of 18 percent strength by weight hydrochloric acid. A solution of 100 parts of NaNO2 in 140 parts of water are run in at 80 C., resulting in the uniform evolution of nitrogen. The mixture is cooled, 500 parts of water are added and the product is filtered off. 182 parts (95% of theory) of 3,5-dichlorobenzoic acid of melting point 178-180 C. are obtained.

Reference： [1]Journal of Chemical Research,2018,vol. 42,p. 579 - 583
[2]Patent: US3931300,1976,A
[3]Patent: US4172098,1979,A
[4]Patent: US4172098,1979,A
[5]Patent: US4172098,1979,A

27
[ 541-42-4 ]
[ 118-92-3 ]
[ 51-36-5 ]

Yield	Reaction Conditions	Operation in experiment
75%	With chlorine; In hydrogenchloride; ethanol; water;	EXAMPLE 12 137 parts of 2-aminobenzoic acid are introduced into 800 parts of ethanol, 50 parts of hydrochloric acid (20% strength of weight) and 500 parts of water. 163 parts of chlorine gas are passed in over 2 hours at 80 C. 300 parts of hydrochloric acid (36 percent strength by weight) are added. 125 parts of isopropyl nitrite are introduced in the course of 7 hours at 80 C. The mixture is cooled, 800 parts of water are added and the product is filtered off. 143 parts of 3,5-dichlorobenzoic acid (75% of theory) of melting point 173-178 C. are obtained.

Reference： [1]Patent: US4172098,1979,A

28
[ 463-73-0 ]
[ 51-36-5 ]
[ 60211-57-6 ]

Yield	Reaction Conditions	Operation in experiment
10.5 g (74%)	With sodium tetrahydroborate; triethanolamine;	(i) 3,5-Dichlorobenzyl Alcohol Prepared according to the method described in Example X(i) above from 3,5-dichlorobenzoic acid (15.3 g; 80 mmol), TEA (8.9 g; 88 mmol), i-Bu chloroformate (12 g; 88 mmol) and NaBH4 (9.0 g; 240 mmol), yielding 10.5 g (74%) of sub-title compound. 1H-NMR (400 MHz; CDCl3): delta 7.27 (t, 1H); 7.28 (d, 2H); 4.68 (s, 2H).

Reference： [1]Patent: US6255301,2001,B1

29
[ 1009093-44-0 ]
[ 51-36-5 ]
[ 1009094-79-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium acetate; caesium carbonate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In dimethyl sulfoxide; at 40℃;	A flask containing boronate (30 mg, 0.05 mmol, 1 eq.), 3,4-dichlorobenzoic acid (20 mg, 0.1 mmol, 2 eq.), S-Phos (2 mg, 0.005 mmol, 0.1 eq.), potassium phosphate (50 mg, 0.2 mmol, 4 eq.) and a dash of palladium acetate was purged with argon and THF (2 mL) added. The mixture was heated at 40 overnight. The reaction mixture acidified with 6M HCl and extracted with DCM. The combined organic layers were dried on Na2SO4 and concentrated to a brown oil. To an aliquot containing this crude oil (0.05 mmol, 1 eq.) in DMF (1 mL) was added (S)-N1,N1-dimethyl-3-phenylpropane-1,2-diamine (30 uL, 0.15 mmol, 3 eq.) and HBTU (30 mg, 0.08 mmol, 1.5 eq.). When the reaction appeared complete by HPLC, the mixture was diluted with MeOH (1 mL) and purified by reverse-phase HPLC (MeCN/40 mM ammonium formate 25%?80%) to give 255 as a white solid (3 mg, 8%). MS (ESI(+)) m/e 761.7 (M+H)+.

Reference： [1]Patent: US2008/114167,2008,A1 .Location in patent: Page/Page column 198-199

30
[ 67-56-1 ]
[ 51-36-5 ]
[ 2905-67-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; for 5.0h;Heating / reflux;	Step 1; Production of methyl 3,5-dichlorobenzoate To a solution of 50 g of 3,5-dichlorobenzoic acid in 120 g of methanol, 10 g of concentrated sulfuric acid was added and the mixture was heated and refluxed for 5 hours. After the reaction solution was cooled to room temperature, the solvent was distilled off under reduced pressure. The resulting residue was dissolved in 200 g of ethyl acetate, washed with water (200 g x 2) followed by washing with saturated sodium hydrogen carbonate solution, and then washed with water. After an organic layer was dried with anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to obtain 48.6 g of aimed product as white solid. 1H NMR (CDCl3, Me4Si, 300 MHz) delta 7.90 (s, 2H), 7.54 (s, 1H), 3.94 (s, 3H).
	With sulfuric acid; for 5.0h;Reflux;	Step 1: Synthesis of methyl 3,5-dichlorobenzoate 10 g of concentrated sulfuric acid was added to a methanol (120 g) solution of 50 g of 3,5-dichlorobenzoic acid, and the mixture was refluxed by heating for 5 hours. After cooling the reaction solution to room temperature, the solvent was distilled off under reduced pressure. The obtained residue was dissolved into 200 g of ethyl acetate, washed with water (200 g x 2), then washed with a saturated aqueous solution of sodium bicarbonate, and further washed with water. After drying the organic phase over anhydrous magnesium sulfate, 48.6 g of the target product was obtained as a white solid by removing the solvent by distilling under reduced pressure. 1H-NMR (CDCl3, Me4Si, 300 MHz) delta 7.90 (s, 2H), 7.54 (s, 1H), 3.94 (s, 3H).

Reference： [1]Zeitschrift fur Naturforschung, B: Chemical Sciences,2008,vol. 63,p. 1291 - 1299
[2]Patent: EP1975149,2008,A1 .Location in patent: Page/Page column 62
[3]Patent: EP2172462,2010,A1 .Location in patent: Page/Page column 73; 86

31
[ 51-36-5 ]
[ 82477-67-6 ]

Yield	Reaction Conditions	Operation in experiment
		(i) 3-chloro-5-methoxybenzoic acid Sodium methoxide (22 g) was added to a stirred solution of 3,5-dichlorobenzoic acid (25 g) in HMPA (140 ml) and heated at 170 C. for 48 h. The reaction was poured onto 1M HCl (400 ml) and the mixture poured onto ice. The resulting solid formed was filtered and washed with water, then dried in vacuo to give the subtitle compound (15.2 g). 1H NMR DMSO-d6: delta 13.34 (1H, s), 7.46 (1H, s), 7.38 (1H, s), 7.30 (1H, s), 3.77 (3H, s).

Reference： [1]Patent: US2008/293775,2008,A1 .Location in patent: Page/Page column 25

32
5-tert-butyl-1-(2-hydroxy-3-methoxypropyl)azepan-2-one [ No CAS ]
[ 51-36-5 ]
1-(5-tert-butyl-2-oxoazepan-1-yl)-3-methoxypropan-2-yl 3,5-dichlorobenzoate [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2008,vol. 47,p. 6233 - 6235

33
[ 67-56-1 ]
[ 51-36-5 ]
[ 82477-67-6 ]

Reference： [1]Archiv der Pharmazie,2011,vol. 344,p. 197 - 204

34
[ 51-36-5 ]
[ 1350473-76-5 ]
[ 1350473-82-3 ]

Yield	Reaction Conditions	Operation in experiment
36%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 0 - 80℃;Inert atmosphere;	General procedure: A mixture of compound 8 (50 mg, 0.1 mmol), 3,4-dichlorobenzoic acid (38 mg, 0.2 mmol), HOBt (36 mg, 0.3 mmol), and EDCI (38 mg, 0.2 mmol) in DMF (1.0 mL) was cooled to 0 C under nitrogen atmosphere. Triethylamine (0.03 mL, 0.2 mmol) was added thereto at the same temperature. The mixture was then stirred at 80 C for 12 h. The reaction mixture was cooled and then partitioned between H2O and ethyl acetate. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3 x 5 mL). The combined organic layer extracts were washed with brine and dried over anhydrous Na2SO4. After evaporation of the organic solvent, the residue was purified by column chromatography (silica gel, hexane-ethyl acetate 1:1 v/v) to yield compound 13 (26 mg, 36.6%).

Reference： [1]European Journal of Medicinal Chemistry,2011,vol. 46,p. 5754 - 5762

35
[ 117757-68-3 ]
[ 1765-93-1 ]
[ 51-36-5 ]
[ 1350760-11-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 115℃; for 0.5h;Inert atmosphere; microwave irradiation; sealed vial;	3,5-Dichloro-4-iodobenzoic acid (400 mg, 1.26 mmol) and 4-fluorophenylboronic acid (220 mg, 1,58 mmol) in a 20 mL microwave reaction vial were taken up in dioxane (10 niL) and 2M K2C03 solution (3.2 mL, 6.4 mmol) and the vial was flushed with nitrogen. Pd(Ph3P)4 (84 mg, 0.076 mmol) was added and the vial was again flushed with nitrogen and sealed. The reaction was heated at 115 C for 30 minutes. The reaction was diluted with water and 2M HC1 and extracted twice with ethyl acetate. The organic layers were washed with brine, dried over sodium sulfate and concentrated. The residue was purified on silica gel (CF 12 gm column, 100% DCM, then 5% ethyl acetate DCM, then a gradient of 5-20% ethyl acetate containing 1% HOAc/DCM) to give a single band by TLC (280 mg) containing a mixture of title compound and 3,5- dichloro benzoic acid bi-product by LC-MS. The mixture was used directly in Step B,

Reference： [1]Patent: WO2011/146324,2011,A1 .Location in patent: Page/Page column 73; 74

36
[ 51-36-5 ]
[ 162167-97-7 ]
[ 1416984-77-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 119 - 124

37
[ 140645-53-0 ]
[ 51-36-5 ]
[ 1416984-78-5 ]

Yield	Reaction Conditions	Operation in experiment
	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 16h;

Reference： [1]Giordanetto, Fabrizio; Wållberg, Andreas; Knerr, Laurent; Selmi, Nidhal; Ullah, Victoria; Thorstensson, Fredrik; Lindelo, Asa; Karlsson, Staffan; Nikitidis, Grigorios; Llinas, Antonio; Wang, Qing-Dong; Lindqvist, Anders; Högberg, Ågot; Lindhardt, Emma; Astrand, Annika; Duker, Göran [Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 1, p. 119 - 124]

38
[ 51-36-5 ]
[ 270912-72-6 ]
[ 1416984-79-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 119 - 124

39
[ 392331-66-7 ]
[ 51-36-5 ]
[ 1416984-83-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 119 - 124

40
[ 64-17-5 ]
[ 51-36-5 ]
[ 91085-56-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid;Reflux;	General procedure: To a stirred solution of different benzoic acids (6.42 mmol) in ethanol (3 mL) was added H2SO4 (0.1mL) and heated to reflux for 6-10 h. The reaction mixture was diluted with ethyl acetate followed by water. The organic layer was washed with saturated NaHCO3 followed by water and brine solution. The organic layer was dried over sodium sulphate, filtered and evaporated to obtain the respective ethyl benzoate derivatives.
	With sulfuric acid; for 10h;Reflux;	General procedure: A mixture of benzoic acid (6.42 mmol), catalytic quantity of conc. H2SO4 in ethanol was heated to reflux for 10 h. The reaction mixture was diluted with ethyl acetate followed by water. The organic layer was washed with saturated NaHCO3 followed by water and brine solution. The organic layer was dried over sodium sulphate, filtered and evaporated to obtain respective ethyl benzoates.
	With sulfuric acid; for 10h;Reflux;	General procedure: Benzoic acids a-j(8.12 mmol) was dissolved in ethanol (15 mL) and added catalytic qty of conc.H2SO4and heated to reflux for 10 h. Ethanol was evaporated and the obtained residue was diluted with ethylacetate (25 mL). The organic layer was washed with aqueous saturated NaHCO3(3 X 15 mL) followed by water (2 X 15 mL) and brine solution (20 mL). The organic layer was separated, dried over sodium sulphate, filtered and evaporated to obtain respective ethyl benzoates.

	With sulfuric acid;Reflux;	General procedure: Benzoicacids (1-5, 2g, 16.40mmol) and2-phenylaceticacid (6-10, 2g, 14.69 mmol) wasdissolved in ethanol (25 mL) and then catalyticquantity of concentrated sulphuric acid was addedand reuxed for 10-12h. Ethanol was concentrated upto 80% and diluted with ethylacetate (50 mL) followedby water (25 mL). The organic layer was washedwith saturated NaHCO3solution (4 X 20 mL), waterand brine solution. The separated organic layer wasdried on sodium sulphate, fltered and concentratedto obtain the corresponding ethylbenzoates (11-15)and ethyl-2-phenylacetates (16-20) in 75-80% yield.The isolated compounds were utilized in the next stepwithout any further purifcation.
	With sulfuric acid; at 80℃; for 7h;	General procedure: Taking 6a as an example, a mixture of benzoic acid (2.5 g,20.0 mmol), 4 mL sulfuric acid, and 50 mL ethanol was heated under reflux for 7 h (hour, h). After finishing the reaction, it was poured into water and extracted by ethylacetate, dried with anhydrous Na2SO4, and then the solventof the organic phase was evaporated under vacuum to give colorless liquid 4a. Then excess 80% N2H4·H2O and 15 mLof ethanol were added into the flask containing 4a, which was heated under reflux about 5 h. After the reaction was completed, it should be cooled into room temperature overnight and the white solid 5a was given after being filtered, washed with ethanol and dried in open air. Finally, 5a (1.4 g,8.0 mmol) was then subjected to substitution reaction with KOH (0.9 g, 15.6 mmol) and CS2(1.2 g, 15.0 mmol) togenerate intermediate 6a. At the same time, 6b-6m was synthesized by the methods described in the literature (Shi et al.2015; Du et al. 2013).

Reference： [1]Journal of Heterocyclic Chemistry,2013,vol. 50,p. 945 - 948
[2]Asian Journal of Chemistry,2015,vol. 27,p. 3605 - 3608
[3]Asian Journal of Chemistry,2016,vol. 28,p. 639 - 643
[4]Oriental Journal of Chemistry,2016,vol. 32,p. 2155 - 2161
[5]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2016,vol. 55B,p. 207 - 212
[6]Oriental Journal of Chemistry,2017,vol. 33,p. 971 - 978
[7]RSC Advances,2018,vol. 8,p. 6306 - 6314
[8]Chemical Papers,2019,vol. 73,p. 17 - 25

41
[ 51-36-5 ]
[ 1462259-91-1 ]
[ 1462260-11-2 ]

Yield	Reaction Conditions	Operation in experiment
39.1%	With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 0℃; for 2.66667h;Inert atmosphere;	To a suspension of <strong>[51-36-5]3,5-dichlorobenzoic acid</strong> (0.044 g, 0.23 mmol) in CH2Cl2 (1.0 mL) at 0 C. under Ar was added DCC (0.048 g, 0.23 mmol). Then a solution of compound 45 (0.061 g, 0.20 mmol) in CH2Cl2 (1.0 mL) was added followed by addition of DMAP (3.7 mg, 0.030 mmol). After 2 hours and 40 minutes, reaction was quenched with saturated NH4Cl, diluted with Et2O, extracted three times with Et2O, washed two times with water, washed 5 times with 1M NaOH, washed 2 times with brine, dried over Na2SO4, and concentrated under reduced pressure. Purification by flash chromatography on silica gel (hexanes-10% EtOAc/hexanes) afforded compound 70 (0.037 g, 39.1%) as a yellow oil.

Reference： [1]Patent: US2013/261133,2013,A1 .Location in patent: Paragraph 0161

42
[ 51-36-5 ]
[ 1452849-33-0 ]
[ 1452849-35-2 ]

Yield	Reaction Conditions	Operation in experiment
64%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 0 - 80℃; for 24h;Inert atmosphere;	A mixture of compound 4 (18.6 mg, 0.06 mmol), the appropriate carboxylic acid derivative (0.12 mmol), HOBt (18.1 mg, 0.13 mmol), and EDCI (29.1 mg, 0.15 mmol) in dry DMF (1.0 mL) was cooled to 0 C under nitrogen atmosphere. To the reaction mixture, triethylamine (0.002 mL, 0.015 mmol) was added at 0 C. The mixture was then stirred at 80 C for 24 h. The reaction mixture was cooled and then partitioned between water (5 mL) and ethyl acetate (5 mL), and the organic layer was separated. The aqueous layer was then extracted with ethyl acetate (3 × 3 mL), and the combined organic extracts were washed with brine and dried over anhydrous Na2SO4. After evaporation of the organic solvent, the residue was purified by column chromatography (silica gel, using the proper ratio of hexane and ethyl acetate) to yield the target diarylamide compound.

Reference： [1]Bulletin of the Korean Chemical Society,2013,vol. 34,p. 1848 - 1852

43
[ 51-36-5 ]
[ 2978-58-7 ]
[ 23950-58-5 ]

Reference： [1]Organic Process Research and Development,1999,vol. 3,p. 172 - 176

44
[ 51-36-5 ]
tert-butyl 4-(azetidin-3-ylmethoxy)-5-cyclopropyl-2-fluorobenzoate [ No CAS ]
tert-butyl 5-cyclopropyl-4-((1-(3,5-dichlorobenzoyl)azetidin-3-yl)methoxy)-2-fluorobenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 18h;	A mixture of 3, 5-dichlorobenzoic acid (100 mg, 0.52 mmol) , tert-butyl 4- (azetidin-3-ylmethoxy) -5-cyclopropyl-2-fluorobenzoate (140 mg, 0.44 mmol) , EDCI (140 mg, 0.72 mmol) and DMAP (27 mg, 0.22 mmol) in DCM (5 mL) was stirred at room temperature for 18 h. The mixture was diluted with DCM (10 mL) and washed with HCl (2 N, 15 mL × 2) . The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (eluting with petroleum ether/EtOAc 4/1) to give the target compound (200 mg, 92) as a white solid. LCMS (ESI) m/z: 437.9 [M+H-56]+.

Reference： [1]Patent: WO2015/78374,2015,A1 .Location in patent: Page/Page column 247

45
5-carboxyphenylene-1,3-bisdiazonium tetrafluoroborate [ No CAS ]
[ 79-06-1 ]
[ 51-36-5 ]
3-(3-amino-2-chloro-3-oxopropyl)-5-chlorobenzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21%; 40%	With copper(II) tetrafluroborate hexahydrate; sodium chloride; In water; acetone; at -25 - 10℃; for 1h;	5-Carboxyphenylene-1,3-bisdiazonium tetrafluoroborate (7.6 g, 0.022 mol) was added to a mixture of 1.7 g (0.024 mol) of acrylamide, 0.8 g (0.0023 mol) of copper(II) tetrafluorborate hexahydrate, and 2.8 g (0.048 mol) of sodium chloride in 150 mL of a water-acetone (1 : 2.5) mixture over 30 min. After nitrogen evolution had ceased (60 min), 30 mL of water was added, and the mixture was extracted with 50 mL of methylene chloride. The organic layer was separated, washed with water, dried over anhydrous calcium chloride, and evaporated. The residue was incubated at -20C till complete crystallization and then recrystallized from methanol to yield 2.3 g (40%) of compound I and 0.9 g (21%) of 3,5-dichlorobenzoic acid melting at 183C (methanol).

Reference： [1]Russian Journal of General Chemistry,2015,vol. 85,p. 1821 - 1825
Zh. Obshch. Khim.,2015,vol. 85,p. 1821 - 1825

46
[ 51-36-5 ]
N-[3-(8-aminoimidazo[1,2-a]pyrazin-3-yl)phenyl]-3-chloro-4-fluorobenzamide [ No CAS ]
3-chloro-N-(3-{8-[(3,5-dichlorobenzoyl)amino]imidazo[1,2-a]pyrazin-3-yl}phenyl)-4-fluorobenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With pyridine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; at 70℃;	General procedure: A mixture of compound 13g (100 mg, 0.26 mmol), pyridine(2 ml), N-(3-dimethylaminopropyl)-N?-ethylcarbodiimide hydrochloride(126 mg, 0.66 mmol) and the benzoic acid derivative(0.66 mmol) was stirred at 70 C overnight.Method A: The solvent was evaporated and the residue wastaken up in chloroform. The organic layer was washed with water(2), dried over sodium sulphate, filtered and concentrated underreduced pressure. The crude product was triturated with diisopropylether, filtered and washed with acetonitrile to give thedesired products.Method B: The solvent was evaporated. The residue was trituratedwith diisopropyl ether, filtered and washed with acetonitrileto give the desired products

Reference： [1]European Journal of Medicinal Chemistry,2016,vol. 108,p. 623 - 643

47
[ 51-36-5 ]
4-((2-aminobenzo[d]thiazol-6-yl)oxy)-N-methylpicolinamide [ No CAS ]
4-((2-(3,5-dichlorobenzamido)benzo[d]thiazol-6-yl)oxy)-N-methylpicolinamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 24h;Inert atmosphere;	General procedure: To a mixture of compound 3 (0.05g, 0.17 mmol) and the appropriate aromatic carboxylic acid (0.34 mmol) in anhydrous DMF (2 mL) under argon atmosphere, DIPEA (0.128 mL, 0.72 mmol) and HATU (0.168 g, 0.442 mmol) were added. The reaction mixture was stirred at rt for 24h or at 80C for 20h (for only 4i), and then quenched with water (30 mL). The aqueous layer was extracted with ethyl acetate (3×20 mL) and the combined organic layers were washed with water and brine, dried over anhydrous Na2SO4, filtered, and the solvent was removed under reduced pressure. The resultant residue was purified by flash column chromatography on silica gel using the proper elution system to furnish the target compounds 4a-i in pure form. 4.3.4 4-((2-(3,5-Dichlorobenzamido)benzo[d]thiazol-6-yl)oxy)-N-methylpicolinamide (4d) Flash column chromatography was performed using a mixture of hexane and ethyl acetate (1:1 then 1:2 v/v). White solid; yield 100%; mp 242-244 C; IR (KBr) nu/cm-1: 3404, 3374, 3167, 3063, 2929, 1664, 1596; 1H NMR (400 MHz, DMSO-d6) delta 13.18 (br. s, 1H, NHCO), 8.78 (d, J = 4.8 Hz, 1H, CONHCH3), 8.53 (d, J = 5.6 Hz, 1H, Py-H6), 8.15 (d, J = 1.6 Hz, 2H, Ph-H2,H6), 7.96 (d, J = 2.4 Hz, 1H, Py-H3), 7.90-7.87 (m, 2H, BT-H4, Ph-H4), 7.43 (d, J = 2.4 Hz, 1H, BT-H7), 7.33 (dd, J = 8.8, 2.4 Hz, 1H, Py-H5), 7.19 (dd, J = 5.6, 2.4 Hz, 1H, BT-H5), 2.80 (d, J = 4.8 Hz, 3H, CH3); 13C NMR (100 MHz, DMSO-d6) delta 166.36, 164.20, 152.98, 150.91, 149.94, 135.70, 134.97, 133.62, 133.42, 132.50, 128.47, 127.61, 122.45, 122.23, 120.47, 114.85, 114.61, 109.46, 26.47; HRMS (ESI-TOF) m/z calcd for C21H14Cl2N4O3SNa [M+Na]+: 495.0062, found: 495.0069.

Reference： [1]European Journal of Medicinal Chemistry,2016,vol. 115,p. 201 - 216

48
[ 65408-91-5 ]
[ 51-36-5 ]
(2R,3R,3aR,7aS)-5-oxo-2-phenyl-3,3a,5,7a-tetrahydro-2H-furo[3,2-b]pyran-3-yl 3,5-dichlorobenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 20℃;	General procedure: A mixture of altholactone (1.0 eq), acid derivatives (1.2 eq), N,N?-dicyclohexylcarbodiimide(1.2 eq), and 4-dimethylaminopyridine (cat.) in dry dichloromethane (2 ml) was stirred atroom temperature for 2 h to overnight. The reaction mixture was monitored by TLC (ethylacetate-hexane). Removal of the solvent was performed under reduced pressure and theresidue was further purified by column chromatography on preparative TLC (silica gel) togive the ester derivatives.

Reference： [1]Journal of Asian Natural Products Research,2016,vol. 18,p. 462 - 474

49
[ 51-36-5 ]
[ 79-19-6 ]
5-(3,5-dichlorophenyl)-1,3,4-thiadiazole-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50.36%		The 9.74g (50mmol) 2,4-dichlorobenzene formic acid, 4.65g (50mmol) thiosemicarbazide, 13mlPOCl3with reflux device placed in round-bottom flask, in 75 C reflux reaction under 1h, cooling to room temperature, with a constant voltage dropping funnel to the round-bottom flask slowly adding 55 ml water, for 110 C reflux reaction 4h, cooling to room temperature, with 50% sodium hydroxide solution accent PH value to 8, and a circulating water type vacuum pump is used, the solid is recrystallized with ethanol, dry to get pale yellow objects 6.21g, yield: 50.36%

Reference： [1]Patent: CN105384736,2016,A .Location in patent: Paragraph 0008

50
[ 51-36-5 ]
[ 110-83-8 ]
C₁₃H₁₂Cl₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With di-tert-butyl peroxide; cobalt(II) chloride; In 1,2-dichloro-ethane; at 120℃; for 18h;Inert atmosphere; Molecular sieve; Sealed tube; Glovebox;	General procedure: A DCE solution (1 mL) was prepared under argon consisting of carboxylic acids (0.5 mmol), 2a (512 muL, 5.0 mmol, 10.0 equiv.), CoCl2 (6.5 mg, 0.05 mmol,10.0 mol%), DTBP (189 muL, 1.0 mmol, 2.0 equiv.), and molecular sieves (4A, 165.0 mg) in a sealed reaction tube with a stir bar. The mixture was then heated to 120 C and reacted for 18h, thereafter being filtered through diatomite to remove the catalyst. The residue was extracted by diethyl ether (3 × 5mL). Afterwards, the combined organic filtrate was dried by Na2SO4 overnight and concentrated, which was analyzed by GC with biphenyl as internal standard. The respective ester was afforded through purification by column chromatography on silica gel.

Reference： [1]Tetrahedron,2017,vol. 73,p. 2943 - 2948

51
[ 51-36-5 ]
benzyl 1-(aminomethyl)-6-azaspiro[2.5]octane-6-carboxylate [ No CAS ]
benzyl 1-((3,5-dichlorobenzamido)methyl)-6-azaspiro[2.5]octane-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 12h;	To a stirred solution of benzyl 1 -(aminomethyl)-6-azaspiro[2.5] octane-6- carboxylate (930mg, 3 mmol) in DCM (15 mL) was added EDCI (864 mg, 1.5 mmol), HOBT (486 mg, 3.6 mmol), DIPEA (1.2 g, 9 mmol) and <strong>[51-36-5]3,5-dichlorobenzoic acid</strong> (688mg, 3.6 mmol), The reaction mixture was stirred at RT for 12 h, then diluted with DCM (30 mL), washed with brine (30 mL) and extracted with DCM (30 mL x 3). The combined extracts were concentrated under reduced pressure. The crude residue was purified by chromatography on silica gel (hexanes: EtOAc 3:1 to 1:1) to afford benzyl 1-((3,5- dichlorobenzamido)methyl)-6-azaspiro[2.5] octane-6-carboxylate (1 g, 73% yield) as yellow oil. Mass Spectrum (ESI) m/z = 447 (M+H).

Reference： [1]Patent: WO2017/83867,2017,A1 .Location in patent: Paragraph 00309

52
[ 51-36-5 ]
[ 51639-48-6 ]
1-(4-(4-(3,5-dichlorobenzoyl)piperazin-1-yl)phenyl)ethanone [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 5507 - 5520

53
[ 51-36-5 ]
[ 13910-49-1 ]
N-[3-(N-benzyl-N-methylamino)propyl]-3,5-dichlorobenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34%		General procedure: Reaction was carried out under nitrogen atmosphere. In 10mL of DCM, benzoic acid (1 eq), HOBt (1.2 eq) and HBtu (1.2 eq) were added and stirred at room temperature for 10min. A solution of N,N-disubstitutedalkyldiamine 5a-f or commercially available amine (1 eq) and DIEA (15 eq) in DCM was added to the reacting mixture. After stirring at room temperature for 24h, the solvent was removed under reduced pressure and DCM was added to the residue. The solution was washed with a solution of NaHCO3 (5%) then saturated NaCl solution. The organic layer was dried over magnesium sulphate and evaporated under reduced pressure. The crude product was purified by thick layer chromatography (DCM:MeOH(NH3), 9:1 (v/v)) or column chromatography (DCM:MeOH(NH3), 9:1 (v/v)).

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 138,p. 964 - 978

54
[ 51-36-5 ]
[ 68-12-2 ]
[ 153203-80-6 ]

Yield	Reaction Conditions	Operation in experiment
82%		The reaction kettle is added compound XVI (190g, 1.0 muM), anhydrous THF (1L) dissolved, cooling to -78 C, slowly adds by drops positively BuLi (2.5M, 0 . 5L), to maintain the temperature of the reaction 2 hours after DMF slowly adds by drops anhydrously (95g, 1.3 muM), the reaction temperature to room temperature slowly to the disappearance of the raw material, to join the semi-saturated ammonium chloride quenching, ethyl acetate after extracting the concentrated white solid, petroleum ether ethyl acetate system beating shall be required compound XII (179g, 82%).
80%		Take 3,5-dichlorobenzoic acid (191mg, 1mmol) was dissolved in 5mL of anhydrous tetrahydrofuran, and argon protection, followed by cooling to -78 .At this temperature, slowly added dropwise 2N lithium diisopropylamide (LDA) in tetrahydrofuran (0.6 mL, 1.2mmol).Stirring was continued for 0.5 ~ 1h after addition was complete.It was then slowly added dropwise a solution of 0.5mL DMF 2mL of tetrahydrofuran, was added after the reaction was continued for 2h, TLC detection, reaction was almost completed. The residue was quenched with 1N dilute hydrochloric acid and evaporated to dryness. The residue was purified by column chromatography using ethyl acetate and water and the ethyl ester layer to give the title compound 3,5-dichloro-4-formylbenzoic acid (175 mg , 80%).

Reference： [1]Patent: CN106565625,2017,A .Location in patent: Paragraph 0073-0074
[2]Patent: CN104341316,2017,B .Location in patent: Paragraph 0379; 0381; 0382

55
[ 70125-16-5 ]
[ 51-36-5 ]
2-aminoquinolin-8-yl 3,5-dichlorobenzoate [ No CAS ]

Reference： [1]RSC Advances,2017,vol. 7,p. 41955 - 41961

56
[ 70125-16-5 ]
[ 51-36-5 ]
2-aminoquinolin-8-yl 3,5-dichlorobenzoate [ No CAS ]
C₁₆H₁₀Cl₂N₂O₂ [ No CAS ]

Reference： [1]RSC Advances,2017,vol. 7,p. 41955 - 41961

57
[ 70125-16-5 ]
[ 51-36-5 ]
C₁₆H₁₀Cl₂N₂O₂ [ No CAS ]

Reference： [1]RSC Advances,2017,vol. 7,p. 41955 - 41961

58
[ 51-36-5 ]
[ 593-74-8 ]
[ 56961-33-2 ]

Yield	Reaction Conditions	Operation in experiment
		First, 15 g of toluene, 50 mL of dichloromethane was added successively to a 200 mL autoclave,0.1 g of N-hydroxyphthalimide and 0.4 g of cobalt acetylacetonate were dissolved and stirred,Sealed autoclave, replaced with oxygen 3 times, pressurized to 3MPa,The temperature was raised to 30 C and the reaction was allowed to proceed for 1 h. After completion of the reaction, the mixture was cooled to room temperature,Filtering to obtain a solution containing benzoic acid;The above solution was placed in a 1000 mL four-necked flask equipped with a thermometer,And then to the flask by adding 100mL glacial acetic acid, stirring, access to nitrogen protection,The temperature was raised to 40 C, and then 30 mL of chlorine gas was introduced at a rate of 10 mL / min,Oil bath control solution temperature at 30 , reaction 3h,To obtain a solution containing 3,5-dichlorobenzoic acid;To the above solution was added 3 g of a shielding reagent, stirred for 5 min,Then add 10gFormat reagent,For 1 h to give a solution containing 3-methyl-5-chlorobenzoic acid,Said shielding agent is dimethylmercury;Ice bath control solution temperature at 0 ,To the above solution was added 5 mL of 98% concentrated sulfuric acid at a rate of 5 mL / min,And 20 mL of 1 mol / L nitric acid was added thereto to control the reaction temperature at 40 C,For 1 h to give a solution containing 2-nitro-3-methyl-5-chlorobenzoic acid;Dissolve the aboveThe solution was placed in a 1000 mL four-necked flask equipped with a thermometer,A further 1 g of zinc sheet was added to the flask,40 mL 0.1 mol / L NaOH,The oil bath control solution temperature was 70 C,Then stir the reaction for 2h,A solution containing 2-amino-3-methyl-5-chlorobenzoic acid was obtained at the end of the reaction;To the above solution was added 100 mL of dichloromethane,40 mL of N, N'-diisopropylcarbodiimide,5 mL of 1-hydroxybenzotriazole, stirred at room temperature for 2 h,And then control the temperature of ice water bath 0 ,40 mL of methylamine was added dropwise to the solution at 10 mL / min with stirring,After dripping, the insulation reaction 2h,A solution containing 2-amino-5-chloro-N, 3-dimethylbenzamide was obtained at the end of the reaction;The resulting solution was extracted with 100 mL of deionized water and 100 mL of methylene chloride. The resulting organic phase was obtained by using a mixed solution of petroleum ether: ethyl acetate = 1: 10 in a volume ratio to give a solution containing 2- Amino-5-chloro-N, 3-dimethylbenzamide, and the solution was distilled under reduced pressure to give a white solid, 2-amino-5-chloro-N, 3-dimethylbenzamide TheThe invention utilizes N-hydroxyphthalimide and cobalt acetylacetonate as the catalyst to oxidize toluene, which is favorable for oxidizing toluene to benzoic acid under mild conditions. The invention adopts N, N'-diisopropylcarbodiimide As the condensation agent, 1-hydroxybenzotriazole as the condensation activator, to avoid the use of phosgene; the invention simplifies the steps, and the yield has been significantly improved to 92.6%.

Reference： [1]Patent: CN105859574,2016,A .Location in patent: Paragraph 0007

59
[ 710328-02-2 ]
[ 51-36-5 ]
3,5-dichloro-N-(2-(4-ethylpiperazin-1-yl)-4-methylquinolin-6-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52.9%		General procedure: Aromatic carboxylic acid (1.11mmol), EDCI (213mg, 1.11mmol), HOBt (150mg, 1.11mmol) were added into 10ml DCM. The mixture was stirred at rt for 1h. Then Et3N (0.31ml, 2.22mmol) and intermediate 17 (200mg, 0.74mmol) were added. After stirring at rt for 24h, the reaction was washed with 2mol/L NaOH solution (20ml×3) and saturated NH4Cl solution (20ml×1), dried over anhydrous Na2SO4 and then concentrated. The residue was purified by normal phase column chromatography to afford the desired compound.

Reference： [1]European Journal of Medicinal Chemistry,2017,vol. 141,p. 1 - 14

60
[ 51-36-5 ]
1-(2-amino-5-fluoro-4-(2-morpholinopyrimidin-5-yl)phenyl)-N,N-dimethylpyrrolidin-3-amine [ No CAS ]
3,5-dichloro-N-[4-fluoro-5-(2-morpholin-4-ylpyrimidin-5-yl)-2-[rac-(3R)-3-(dimethylamino)pyrrolidin-1-yl]phenyl]benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In dichloromethane; at 20℃; for 18h;	To a solution of <strong>[51-36-5]3,5-dichlorobenzoic acid</strong> (0.025 g, 0.13 mmol) in DCM (1 mL) was added propylphosphonic anhydride (50% solution) (0.08 mL, 0.13 mmol) and triethylamine (0.03 mL, 0.19 mmol). After mixing the clear solution was transferred by pipette to a suspension of (R)-1-(2-amino-5-fluoro-4-(2- mo holinopyrimidin-5-yl)phenyl)-N,N-dimethylpyrrolidin-3 -amine (0.025 g, 0.07 mmol) in DCM (1 mL) at room temperature. After stirring for 18 h at room temperature the reaction was concentrated onto celite and purified by flash chromatography [0.5 - 10% MeOH/DCM + 0.5% NH4OH] to afford the title compound (R)-3,5-dichloro-N-(2-(3-(dimethylamino)pyrrolidin-1-yl)-4-fluoro-5-(2- mo holinopyrimidin-5-yl)phenyl)benzamide (0.021 g, 55 %). l NMR (500MHz, DMSO-d6) delta = 10.17 (s, 1H), 8.52 (s, 2H), 7.99 (d, J=1.8 Hz, 2H), 7.89 (t, J=1.8 Hz, 1H), 7.31 (d, J=8.8 Hz, 1H), 6.67 (d, J=14.1 Hz, 1H), 3.75 - 3.72 (m, 4H), 3.70 - 3.66 (m, 4H), 3.44 - 3.40 (m, 1H), 3.19 (t, J=8.7 Hz, 1H), 2.65 - 2.61 (m, 1H), 2.13 - 2.05 (m, 7H), 1.71 - 1.62 (m, 1H); LCMS [M+H]+: 559.3.

Reference： [1]Patent: WO2017/147700,2017,A1 .Location in patent: Paragraph 00453

61
[ 51-36-5 ]
[ 140-75-0 ]
3,5-dichloro-N -(4-fluorobenzyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With oxygen; potassium carbonate; eosin y; In toluene; at 20℃;Irradiation; Green chemistry;	General procedure: A flame-dried 10 mL flask was charged with amine 2 (0.5 mmol), potassium acetic acid 1 (1.5 mmol), potassium carbonate (2.0 mmol) and toluene (3 mL). Eosin Y (0.01 mmol) was added to the mixture. The mixture was allowed to stir at room temperature opening in air, and be irradiated with a Luxeon Rebel high power green LEDs [2.50 W, lambda = 535 nm] for 60-180 min. at room temperature, until all of the starting material disappeared. Then, the mixture was poured into water (10 mL), extracted with EtOAc (4 * 10 mL), washed with brine (15 mL), and dried over Na2SO4. The crude organic phase was concentrated in vacuo and purified with a short flash column chromatography (silica gel, hexane/EtOAc = 5:1) to afford the corresponding product 3(a-n) in high yield (71-95%) in Table 2.

Reference： [1]Nature Chemistry,2017,vol. 9,p. 571 - 577
[2]Tetrahedron Letters,2019,vol. 60,p. 40 - 43

62
[ 51-36-5 ]
[ 104004-96-8 ]
3,5-dichloro-N-(4-((8S,11R,13S,14S,17S)-17-hydroxy-13-methyl-3-oxo-17-(prop-1-yn-1-yl)-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-11-yl)phenyl)-N-methylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 16h;Inert atmosphere;	General procedure: A round-bottom flask was charged with carboxylic acid (1.2-2.0 equiv), compound 2 (1.0 equiv) and EDCI (3.0 equiv). Dichloromethane was added (0.1-0.2M), and the mixture was allowed to stir at room temperature until compound 2 was consumed (determined by TLC).

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 146,p. 354 - 367

63
[ 51-36-5 ]
C₁₃H₁₅F₂N₅*ClH [ No CAS ]
C₂₀H₁₇Cl₂F₂N₅O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In acetonitrile; at 20℃; for 3h;	To a stirred solution of intermediate 25a (100 mg, 0.317 mmol) in dry ACN (5 mL), was added <strong>[51-36-5]3,5-dichlorobenzoic acid</strong> (72.593 mg, 0.38 mmol). TEA (0.22 mL, 1.58 mmol) was added, followed by 1-propanephosphonic anhydride ([68957-94-8], 0.28 mL, 0.48 mmol) and the mixture was stirred at RT for 3 h, giving a white precipitate in a brown solution. The solvent was removed in vacuo, and the crude was partitioned between DCM (10 mL) and a saturated aqueous NaHC03 solution (10 mL). The OL was washed with a saturated aqueous Na2C03 solution (1x15 mL), dried (MgSC^), filtered, the solvent was removed in vacuo, and coevaporated with toluene (1x20 mL), giving a white precipitate in a brown solution, which was dried overnight to give brown and white crystals. Recrystallisation from Et20 yielded off white crystals, which were oven dried overnight in a 40C vaccum oven, giving compound 333 (88 mg, 61%), as off white crystals

Reference： [1]Patent: WO2018/83098,2018,A1 .Location in patent: Page/Page column 70

64
[ 51-36-5 ]
(3S,6S)-3-((1H-indol-3-yl)methyl)-6-(3-aminopropyl)piperazine-2,5-dione [ No CAS ]
N-(3-((2S,5S)-5-((1H-indol-3-yl)methyl)-3,6-dioxopiperazin-2-yl)propyl)-3,5-dichlorobenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; N,N-dimethyl-formamide; at 0 - 20℃;	General procedure: Compound 5a (300mg, 1mmol), benzoic acid (146mg, 1.2mmol), HOBt (162mg, 1.2mmol), Et3N (121mg, 1.2mmol) and EDCI (230mg, 1.2mmol) were added to 5mL of DMF and 20mL of dichloromethane, and the mixture was cooled to 0C under stirring for 1h and then stirred at room temperature overnight. The reaction liquid was washed by water (10mL×3). The organic phase was dried over anhydrous magnesium sulfate and purified with silica gel flash column chromatography to afford N-(3-((2S,5S)-5-((1H-indol-3-yl)methyl)-3,6-dioxopiperazin-2-yl)propyl) benzamide (10a) as pale yellow liquid in 71% yield. Compounds 10b-j were prepared similar to 10a.

Reference： [1]Chinese Chemical Letters,2018,vol. 29,p. 977 - 980

65
[ 51-36-5 ]
[ 126918-33-0 ]
C₁₇H₁₂Cl₂F₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%		<strong>[51-36-5]3,5-dichlorobenzoic acid</strong> (0.20 g, 0.97 mmol), triphenylphosphFin (0.26 g, 0.97 mmol), diisopropyl azodicarboxylate (0.20 g, 0.97 mmol) was mixed with toluene (0.68 g), cooled to 0 C.The mixture was stirred for about 1.5 hours, and a solution of the compound (3) (0.15g, 0.75 mmol) was added dropwise and the mixture was stirred for 2 hours. The obtained reaction solution was directly used as SiriPurification by Kagel column chromatography gave compound (21) (0.27 g, yield 96%) As a pale yellow liquid.

Reference： [1]Patent: JP2018/131420,2018,A .Location in patent: Paragraph 0067

66
[ 331959-40-1 ]
[ 51-36-5 ]
5-(3,5-dichlorobenzamido)-3-methyl-N₂-phenylthiophene-2,4-dicarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%		General procedure: To a solution of a carboxylic acid derivative (0.4mmol) in anhydrous DMF (1mL) was added PyAOP (0.42mmol) and DIEA (0.8mmol). The resulting mixture was stirred at rt for 30min before 5-amino-3-methyl-N2-phenylthiophene-2,4-dicarboxamide (0.4mmol) was added. This reaction mixture was stirred at rt overnight, and quenched by adding H2O (5mL). The aqueous was extracted with EtOAc (4×15mL, and the combined organics were washed with brine (2×40mL) and dried over MgSO4. Solvent was removed and the residue was purified by flash chromatography on silica gel using hexanes: EtOAc (3:2) to obtain 12a-k.
54%		5-(3,5-Dichlorobenzamido)-3-methyl-N2-phenylthiophene-2,4-dicarboxamide (ZW-1040) To the solution of <strong>[51-36-5]3,5-dichlorobenzoic acid</strong> (76 mg, 0.40 mmol) in anhydrous DMF (1 mL), was added PyAop (219 mg, 0.42 mmol) and DIEA (139 mul, 0.80 mmol), this reaction mixture was stirred at room temperature for 30 min, then 5-amino-3-methyl-N2-phenylthiophene-2,4-dicarboxamide (110 mg, 0.40 mmol) was added. This reaction mixture was stirred at rt for overnight. Quenched this reaction by adding H2O (5 mL), the aqueous solution was extracted with EtOAc (415 mL). The EtOAc portions were combined, washed with brine (240 mL), dried over MgSO4, and removed the solvent. The residue was purified by chromatography on silica (gradient elution from hexanes the residue was purified by flash chromatography on silica gel using hexane:EtOAc (3:2) to obtain desired compounds 89 mg (54%). 1H NMR: (CD3OD) delta 7.63 (d, J=7.8 Hz, 2H), 7.37 (m, 4H), 7.11 (m, 2H), 2.47 (s, 3H).

Reference： [1]European Journal of Medicinal Chemistry,2019,vol. 164,p. 179 - 192
[2]Patent: US2019/92742,2019,A1 .Location in patent: Paragraph 0131

67
[ 102-06-7 ]
[ 51-36-5 ]
N,N′ -diphenylguanidinium 3,5-dichlorobenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; for 5.0h;	DPGCB was prepared by mixing a 1:1 ratio of N,N?-<strong>[102-06-7]diphenylguanidine</strong> and 3,5-dichlorobenzoic acid, using methanol as a solvent. The homogeneous-saturated solution was stirred well for 5 hr and the filtrate was kept in a glass beaker covered with a perforated aluminum foil forthe growth of pure single crystals of DPGCB at room temperature.optically transparent crystals harvested after 25 days were recrystallized using acetone solvent to enhance their optical quality. The formation of DPGCB is shown in the scheme below.

Reference： [1]Journal of Physics and Chemistry of Solids,2019,vol. 130,p. 69 - 83

68
[ 51-36-5 ]
4-(((7-azaspiro[3.5]decane-2-yl)methoxy)methyl)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide hydrochloride [ No CAS ]
5-cyclopropyl-4-(((7-(3,5-dichlorobenzoyl)-7-azaspiro[3.5]indol-2-yl)methoxy)methyl)-2-fluoro-N-(methylsulfonyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 4h;	4-(((7-Azaspiro[3.5]decan-2-yl)methoxy)methyl)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)Benzoylamide hydrochloride 1k (300mg, 0.65mmol), <strong>[51-36-5]3,5-dichlorobenzoic acid</strong> 2a (111mg, 0.65mmol), 1-ethyl-3-(3-dimethylaminopropyl) carbon Imine (244 mg, 1.3 mmol) and 4-dimethylaminopyridine (78 mg, 0.65 mmol) were dissolvedThe reaction was carried out for 4 hours at room temperature in 20 mL of dichloromethane. 30 mL of 1 M diluted hydrochloric acid was added to the reaction mixture, and the mixture was combined with methylene chloride (30 mL × 3). Purification of system B) gives 5-cyclopropyl-4-(((7-(3,5-dichlorobenzoyl)-7-azaspiro[3.5]indol-2-yl)methoxy) A 2-fluoro-N-(methylsulfonyl)benzamide 2 (165 mg, white solid), yield: 43%.

Reference： [1]Patent: CN109574927,2019,A .Location in patent: Paragraph 0290-0297

69
[ 51-36-5 ]
[ 259796-12-8 ]

Reference： [1]Patent: CN109574927,2019,A

70
[ 51-36-5 ]
5-cyclopropyl-2-fluoro-4-(((4-fluoropiperidin-4-yl)methoxy)methyl)-N-(methylsulfonyl)benzamide hydrochloride [ No CAS ]
5-cyclopropyl-4-(((1-(3,5-dichlorobenzoyl)-4-fluoropiperidin-4-yl)methoxy)methyl)-2-fluoro-N-(methylsulfonyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 4h;	5-Cyclopropyl-2-fluoro-4-(((4-fluoropiperidin-4-yl)methoxy)methyl)-N-(methylsulfonyl)benzoylAmine hydrochloride 13i (40 mg, 0.09 mmol), 3,5-difluorobenzoic acid 2a (17 mg, 0.09 mmol), 1-ethyl-3 (3-dimethylamine)Propyl)carbodiimide (35 mg, 0.18 mmol) and 4-dimethylaminopyridine (11 mg, 0.09 mmol) dissolved in 5 mL of dichloromethaneThe mixture was reacted at room temperature for 4 hours in an alkane. 10 mL of 1 M dilute hydrochloric acid was added to the reaction mixture, and extracted with dichloromethane (10 mL×3), and combined.The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure.5-Cyclopropyl-4-(((1-(3,5-dichlorobenzoyl)-4-fluoropiperidin-4-yl)methoxy)methyl)-2-fluoro-N- (ASulfonyl)benzamide 14 (20 mg, white solid), yield: 39%.

Reference： [1]Patent: CN109574927,2019,A .Location in patent: Paragraph 0503-0510

71
[ 51-36-5 ]
[ 38330-80-2 ]
methyl 3-(3,5-dichlorophenyl)-3-oxopropanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%		Monomethyl malonate potassium salt (4.06 g, 26 mmol),MgCl2 (2.48 g, 26 mmol) was stirred under reflux in THF (30 mL) overnight to give solution A; N,N'-carbonyldiimidazole (CDI, 3.94 g, 24 mmol)Slowly added to 3,5-dichlorobenzoic acid (3.82 g, 20 mmol) in THF (20 mL).Stir at room temperature for 1 hour to form solution B.Solution B was then slowly added dropwise to solution A at room temperature.After the completion of the dropwise addition, the reaction was stirred at room temperature overnight.It was quenched with 1 M EtOAc (50 mL).The organic phase was combined, washed with brine and dried over anhydrous sodium sulfate.Concentration under reduced pressure gave compound 34A (4.7 g, 95percent yield) as a yellow solid.

Reference： [1]Patent: CN104045552,2019,B .Location in patent: Paragraph 0391; 0392; 0393; 0394

72
[ 51-36-5 ]
2-(3-formyl-2-oxoquinolin-1(2H)-yl)acetohydrazide [ No CAS ]
1-((5-(3,5-dichlorophenyl)-1,3,4-oxadiazol-2-yl)methyl)-1,2-dihydro-2-oxoquinoline-3-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With trichlorophosphate; at 110 - 120℃;Reflux;	General procedure: An equimolar mixture of 2-(3-formyl-2-oxoquinolin-1(2H)-yl)acetohydrazide and different substituted benzoic acid was refluxed in the presence of POCl3 (10-15 mL) for 6-10 h at 110-120 C. After completion of reaction, mixture was cooled at room temperature and poured into crushed ice. On basification of sodium bicarbonate (5 %), solid mass was so separated was washed with water and crystallized from ethanol.

Reference： [1]Asian Journal of Chemistry,2019,vol. 31,p. 1389 - 1397

73
[ 107884-23-1 ]
[ 51-36-5 ]
methyl 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-(3-5-dichlorobenzoyl)piperazin-1-yl)quinoline-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%		A solution of methyl-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(piperazin-1-yl)quinoline-3-carboxylate2g (5.80 mmol) in N,N-dimethylformamide (20 mL), 3-5dichlorobenzoic acid (1.10 g, 5.80 mmol) and DIPEA (2.26mL, 17.40 mmol) were added and stirred at room temperaturefor 20 min, HATU (3.30 g, 8.70 mmol) was added and stirredat room temperature for 6 h. TLC shows completion of startingmaterial. The reaction mixture was quenched with water,extracted with ethyl acetate, the combined organic layer wasdried over sodium sulfate and concentrated under reduced pressure, the obtained crude product was purified by column chromatography using silica gel (100-200 mesh) and 5 %methanol in dichloromethane as eluent, desired organic fractions were distilled under reduced pressure to get methyl-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(4-(3-5-dichlorobenzoyl)piperazin-1-yl)quinoline-3-carboxylate. Yield (45 %,1.35 g), m.p. 232-34 C. 1H NMR (300 MHz, DMSO-d6) deltappm: 1.06 (s, 1H, cyclopropyl CH), 1.32-1.34 (d, 4H, cyclopropylCH2), 3.40 (br-s, 4H, piperazine CH2), 3.60 (br-s, 4H,piperazine CH2), 3.91 (s, 3H, OCH3), 7.42-7.62 (m, 5H), 7.90-7.98 (d, 1H), 8.68 (s, 1H, N-C=C-H). IR (KBr, numax, cm-1):2922 (C-H Ar), 1710 (C=OOCH3), 1700 (C-CO-N), 1680(C=O quinoline), 1564, 1469 (C=C aromatic), 1265 (C-O-C),1380 (C-N st), 974 (C-H cyclopropyl).

Reference： [1]Asian Journal of Chemistry,2019,vol. 31,p. 2000 - 2008

74
[ 51-36-5 ]
[ 951395-08-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: thionyl chloride; N,N-dimethyl-formamide / toluene / 3 h / Reflux 2.1: tetrahydrofuran; lithium hydroxide monohydrate / 20 °C 2.2: 0.5 h 3.1: toluene-4-sulfonic acid / 2 h / Reflux 4.1: lithium hydroxide monohydrate; ethyl acetate; methanol / 30 - 65 °C
	Multi-step reaction with 3 steps 1.1: oxalyl dichloride / tetrahydrofuran 1.2: 3 h / 25 - 35 °C 2.1: toluene-4-sulfonic acid / 40 h / 110 - 140 °C 3.1: propan-2-one / 2 h / 55 - 65 °C
	Multi-step reaction with 4 steps 1.1: oxalyl dichloride / tetrahydrofuran 1.2: 3 h / 25 - 35 °C 2.1: thionyl chloride / tetrahydrofuran / 30 - 50 °C 3.1: toluene-4-sulfonic acid / toluene / 30 °C / Reflux 4.1: lithium hydroxide monohydrate; lithium hydroxide monohydrate / tetrahydrofuran / 15 h / 30 °C 4.2: 6 h / 30 °C

Multi-step reaction with 3 steps 1.1: N,N-dimethyl-formamide; thionyl chloride / toluene / 0.2 h / 60 - 70 °C 2.1: lithium hydroxide monohydrate; tetrahydrofuran / 0.5 h / 15 - 20 °C 2.2: 1.5 h / 35 - 40 °C 3.1: triethylamine / toluene; N,N-dimethyl acetamide / 1 h / 20 - 25 °C 3.2: 0.24 h / 0.11 - 120 °C

Reference： [1]Current Patent Assignee: AZAD PHARMA AG - WO2019/175263, 2019, A1
[2]Current Patent Assignee: NURAY CHEMICALS PRIVATE - WO2022/9221, 2022, A1
[3]Current Patent Assignee: NURAY CHEMICALS PRIVATE - WO2022/9221, 2022, A1
[4]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2022/84790, 2022, A1

75
[ 51-36-5 ]
[ 594839-88-0 ]

Reference： [1]Patent: WO2019/175263,2019,A1

76
[ 51-36-5 ]
C₂₀H₁₈O₃ [ No CAS ]
C₂₇H₂₀Cl₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 16h;	To a solution of H-26 (200 mg, 0.654 mmol), <strong>[51-36-5]3,5-dichlorobenzoic acid</strong> (150 mg, 0.785 mmol), and 4-dimethylaminopyridine (8.0 mg, 0.065 mmol) in dichloromethane (5 mL), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (163 mg, 0.85 mmol) was added at room temperature, and the resulting mixture was stirred at the same temperature for 16 hours. Water was added to the mixture, and extraction was carried out with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous magnesium sulfate, followed by filtration, and concentration under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate, 6:1), to obtain H-192 as white crystals (310 mg, 0.649 mmol, 99 %). Regarding H-192, the NMR measurement spectrum and the result of mass spectrometry by HR-ESI-MS were as follows. 1H NMR (400 MHz, CDCl3) delta3.44 (1H, dd, J = 14.2, 7.8 Hz), 3.50 (1H, dd, J = 14.2, 5.0 Hz), 5.17 (1H, d, J = 12.4 Hz), 5.22 (1H, d, J = 12.4 Hz), 5.59 (1H, dd, J = 7.8, 5.0 Hz), 7.21-7.26 (2H, m), 7.28-7.34 (3H, m), 7.37 (1H, dd, J = 8.7, 1.4 Hz), 7.45-7.51 (2H, m), 7.53 (1H, t, J = 2.3 Hz), 7.71 (1H, s), 7.74-7.84 (3H, m), 7.87 (2H, d, J = 2.3 Hz); 13C NMR (100 MHz, CDCl3) delta37.5, 67.4, 73.9, 125.9, 126.2, 127.3, 127.60, 127.64, 128.2, 128.3, 128.5, 128.6, 132.1, 132.5, 132.8, 133.1, 133.4, 134.9, 135.3, 163.6, 168.9; HRESIMS calcd for C27H20Cl2O4Na [M+Na]+ 501.0636, found 501.0640. The chemical structure of H-192 found was as follows.

Reference： [1]Patent: EP3549930,2019,A1 .Location in patent: Paragraph 0320-0323

77
[ 51-36-5 ]
[ 114-33-0 ]
[ 7732-18-5 ]
[ 6046-93-1 ]
C₂₈H₂₆Cl₄CuN₄O₈*2H₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	for 72h;	General procedure: Complex 1 was prepared by the reaction of an aqueous solution of copper(II) acetate monohydrate (1mmol, 0.20g) with N-methylnicotinamide (2mmol, 0.27g) followed by addition of 4-fluorobenzoic acid (2mmol, 0.28g). The reaction mixture was stirred until a blue product was precipitated (3days). The fine blue microcrystals were filtered off, washed with a small portion of water and dried at ambient temperature. The mother liquor obtained from filtration were left to crystallize. The blue crystals suitable for X-ray structure determination were separated after several days. Yield: 0.41g (65%).

Reference： [1]Polyhedron,2020,vol. 175

78
[ 51-36-5 ]
[ 128915-32-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: thionyl chloride; N,N-dimethyl-formamide / 2 h / Reflux 2: pyridine / N,N-dimethyl-formamide / 2 h / 60 °C / Inert atmosphere

Reference： [1]Zhang, Jun; Li, Yue; Wang, Bei; Jia, Ai-Quan; Zhang, Qian-Feng [Journal of Chemical Crystallography, 2021, vol. 51, # 1, p. 108 - 115]

79
[ 51-36-5 ]
N'-hydroxy-2-((4-methyl-2-oxo-2H-chromen-7-yl)oxy)acetimidamide [ No CAS ]
7-((5-(3,5-dichlorophenyl)-1,2,4-oxadiazol-3-yl)methoxy)-4-methyl-2H-chromen-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%		General procedure: To a solution of carboxylic acid (0.55mmol) in DMSO (1-2ml), CDI (97mg, 0.6mmol) was added. The reaction mixture was stirred at room temperature for 30min and Intermediate 5(124mg, 1mmol) was added. The reaction mixture was stirred at room temperature for another 18h. After that, powdered NaOH (24mg, 0.66mmol) was rapidly added to the reaction mixture and it was allowed to stir at room temperature for 2h. Then the reaction mixture was diluted with cold water (50ml). The resulting precipitate was filtered off and dried. It was subjected to column chromatography using silica gel (60-120 mesh) as stationary phase and EtOAc in hexane (0 percent to 30 percent) as the mobile phase to afford the title compounds (6a-q).

Reference： [1]Bioorganic Chemistry,2020,vol. 98

80
[ 431-35-6 ]
[ 51-36-5 ]
C₁₀H₃Cl₂F₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With dipotassium hydrogenphosphate; bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; silver(I) acetate; In 2,2,2-trifluoroethanol; at 140℃; for 24h;	(1) Add 0.0456 g (0.24 mmol) of <strong>[51-36-5]3,5-dichlorobenzoic acid</strong> to the reaction tube,Pentamethylcyclopentadiene iridium dichloride dimer 0.0040 g (0.005 mmol),Dipotassium hydrogen phosphate 0.0174 g (0.1 mmol), silver acetate 0.040 g (0.24 mmol),0.0382 g (0.2 mmol) of bromotrifluoroacetone and 1 mL of trifluoroethanol,Reaction at 140 for 24 hours; TLC follows the response until it is completely over; The crude product obtained after the reaction is separated by column chromatography (petroleum ether: ethyl acetate = 30: 1),The target product was obtained (yield 66%).

Reference： [1]Organic Letters,2020
[2]Patent: CN111138402,2020,A .Location in patent: Paragraph 0053-0059

81
[ 51-36-5 ]
[ 135484-83-2 ]
C₁₅H₁₀BrCl₂NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With pyridine; trichlorophosphate; In dichloromethane; at 0 - 20℃;	Pyridine (13mL, 153mmol, 10eq) was added to solution of 244.2 (1g, 15.3mmol, 1eq) and <strong>[51-36-5]3,5-dichlorobenzoic acid</strong> (3g, 18.4mmol, 1.2eq) in dry DCM (30mL) at room temperature. POCl3 (15mL, 169mmol, 11eq) was added to reaction mixture at 0 oC and the mixture was allowed to stir at room temperature. After completion of reaction, the reaction mixture was quenched by saturated sodium bicarbonate solution and extracted with DCM (3 x 40mL). Combined organic layer was washed with brine, dried over sodium sulphate and concentrated under reduced pressure to obtain crude material. The crude reaction mixture was purified by column chromatography and compound was eluted in 18% ethyl acetate in hexane to obtain pure 244.3 (1.1 g, 62%). MS(ES): m/z 402.2 [M-H]-.

Reference： [1]Patent: WO2020/97408,2020,A1 .Location in patent: Paragraph 00739

82
[ 51-36-5 ]
[ 800375-15-9 ]
C₂₁H₁₅Cl₂NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 40℃;Inert atmosphere;	Into a 20-mL vial purged and maintained with an inert atmosphere of nitrogen was placed 249.1 (500 mg, 2.20 mmol, 1 equiv), <strong>[51-36-5]3,5-dichlorobenzoic acid</strong> (504.2 mg, 2.640 mmol, 1.2 equiv), DMF (10 mL), DIEA (568.6 mg, 4.400 mmol, 2 equiv), and HATU (1254.8 mg, 3.300 mmol, 1.5 equiv). The resulting solution was stirred overnight at 40 oC in an oil bath. The solution was diluted with 30 mL of H2O, then extracted with 3 x 20 mL of ethyl acetate. The combined organics were concentrated under vacuum. The crude product was purified by re-crystallization from MeOH. This resulted in 597 mg (68%) of 290.1 as a white solid.

Reference： [1]Patent: WO2020/97408,2020,A1 .Location in patent: Paragraph 00852

83
[ 51-36-5 ]
C₁₃H₁₂BrN [ No CAS ]
C₂₀H₁₄BrCl₂NO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28.09%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In dichloromethane; at 25℃; for 12h;	Into a 100-mL round-bottom flask were placed <strong>[51-36-5]3,5-dichlorobenzoic acid</strong> (500 mg, 2.618 mmol, 1 equiv), DCM (20 mL, 314.601 mmol, 120.18 equiv), 312.4 (1372.44 mg, 5.235 mmol, 2 equiv), DIEA (1014.95 mg, 7.853 mmol, 3 equiv), and HATU (1492.97 mg, 3.926 mmol, 1.5 equiv). The resulting solution was stirred for 12 hr at 25 oC. The reaction was then quenched by the addition of water. The resulting solution was extracted with 3x35 mL of ethyl acetate. The combined organic layers were concentrated under vacuum. The residue was applied onto Prep-TLC eluting with ethyl acetate/petroleum ether (5:1) to give 320 mg (28.09%) of 312.5 as a light yellow solid.

Reference： [1]Patent: WO2020/97408,2020,A1 .Location in patent: Paragraph 00908

84
[ 51-36-5 ]
[ 761-65-9 ]
[ 153203-80-6 ]
4,6-dichloro-3-hydroxy-2-benzofuran-1(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3,5-dichlorobenzoic acid With lithium diisopropyl amide In tetrahydrofuran at -50℃; Inert atmosphere; Industrial scale; Stage #2: N,N-dibutylformamide In tetrahydrofuran at -50℃; Inert atmosphere; Industrial scale;

Reference： [1]Imamura, Yoshiaki; Kakinuma, Makoto; Komurasaki, Tadafumi; Matsuura, Takaharu; Nishino, Yutaka; Sato, Yusuke [Organic Process Research and Development, 2020, vol. 24, # 11, p. 2651 - 2656]

85
[ 51-36-5 ]
[ 5980-23-4 ]

Yield	Reaction Conditions	Operation in experiment
48%	With tris[2-phenylpyridinato-C₂,N]iridium(III); dipotassium hydrogenphosphate; borane-ammonia complex; di-<i>tert</i>-butyl dicarbonate; magnesium chloride In acetonitrile at 20℃; for 36h; Schlenk technique; Irradiation; Green chemistry;

Reference： [1]Chen, Xuenian; Kang, Jia-Xin; Ma, Yan-Na; Miao, Yu-Qi [Green Chemistry, 2021, vol. 23, # 10, p. 3595 - 3599]

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

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

[ CAS No. 51-36-5 ] {[proInfo.proName]}

Quality Control of [ 51-36-5 ]

Related Doc. of [ 51-36-5 ]

Product Details of [ 51-36-5 ]

Calculated chemistry of [ 51-36-5 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 51-36-5 ]

Application In Synthesis of [ 51-36-5 ]

[ 51-36-5 ] Synthesis Path-Upstream 1~14

[ 51-36-5 ] Synthesis Path-Downstream 1~85

Related Functional Groups of [ 51-36-5 ]

Chlorides

Carboxylic Acids

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 51-36-5 ]