[ CAS No. 452-83-5 ] {[proInfo.proName]}

Name: 452-83-5|2-Chloro-5-fluoroaniline|98%
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SKU: A109284
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Quality Control of [ 452-83-5 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 452-83-5 ]

Product Details of [ 452-83-5 ]

CAS No. :	452-83-5	MDL No. :	MFCD00084852
Formula :	C₆H₅ClFN	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VWUFOZAFKYOZJB-UHFFFAOYSA-N
M.W :	145.56	Pubchem ID :	2736509
Synonyms :

Calculated chemistry of [ 452-83-5 ]

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	35.81
TPSA :	26.02 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.49 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.64
Log Po/w (XLOGP3) :	2.39
Log Po/w (WLOGP) :	2.49
Log Po/w (MLOGP) :	2.51
Log Po/w (SILICOS-IT) :	2.21
Consensus Log Po/w :	2.25

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.74
Solubility :	0.264 mg/ml ; 0.00181 mol/l
Class :	Soluble
Log S (Ali) :	-2.58
Solubility :	0.385 mg/ml ; 0.00264 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.91
Solubility :	0.179 mg/ml ; 0.00123 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.16

Safety of [ 452-83-5 ]

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 [ 452-83-5 ]

* 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 [ 452-83-5 ]
Downstream synthetic route of [ 452-83-5 ]

[ 452-83-5 ] Synthesis Path-Upstream 1~2

1
[ 345-17-5 ]
[ 452-83-5 ]

Yield	Reaction Conditions	Operation in experiment
84.5%	With tin(ll) chloride In ethanol at 70℃; for 0.5 h;	A mixture of 0.17 g (1 mmol) of 2-chloro-5-fluoronitrobenzene, 1.13 g (5 mmol) of tin (II) chloride dihydrate and 10 ml of EtOH was stirred at 70°C for 0.5 hours. After cooling to room temperature, the mixture was poured into H₂O (30 ml), alkalinized with 10percent Na₂CO₃ and extracted with CH₂Cl₂. The organic layer was dried (Na₂SO₄) and evaporated to dryness to give 0.12 g (84.5percent) of the desired compound. ¹H-NMR (CDCl₃, δ): 4.16 (s, 2H, NH₂), 6.51-6.77 (m, 2H, phenyl CHs), 7.09-7.21 (m, 1H, phenyl CH).

Reference： [1] Patent: EP1200406, 2004, B1, . Location in patent: Page 14
[2] Green Chemistry, 2012, vol. 14, # 11, p. 3164 - 3174,11

2
[ 347-71-7 ]
[ 452-83-5 ]

Reference： [1] Recueil des Travaux Chimiques des Pays-Bas, 1929, vol. 48, p. 1063

[ 452-83-5 ] Synthesis Path-Downstream 1~81

1
[ 347-71-7 ]
[ 452-83-5 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1929,vol. 48,p. 1063

2
[ 452-83-5 ]
[ 1435-49-0 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1929,vol. 48,p. 1063

3
[ 452-83-5 ]
[ 108-24-7 ]
[ 347-71-7 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1929,vol. 48,p. 1063

4
[ 452-83-5 ]
[ 127-68-4 ]
[ 917251-76-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; In water; glycerol; at 140℃; for 2h;	Example 1; Preparation of 6-methoxy-8-[4-(l-(5-fluoro)-qumolin-8-yl-piperidin-4-yI)-piperazin-l- ylj-quinoine (Form A)Step 1: 5-Fluoro-8 chloroquinolineTo a mixture of (5.0 g) 2-chloro-5-fluoroaniline (commercially available, 6.0 g), glycerol (6.0 g) and wi-nitrobenzene sulfonic acid sodium salt (11.0 g), was added 20 mL of 70 % sulfuric acid dropwise. The reaction temperature was raised to 140 C for 2 h. The mixture was then cooled, poured on ice water and filtered through celite. The filtrate was neutralized with NaOH and extracted with CH2CI2. The combined organic layers were dried over anhydrous MgSO4 and concentrated on a rotary evaporator. The crude product was purified by flash chromatography on silica gel using 100% CH2Cl2 to give 3.7 g of the desired product of a yellow solid; MP = 74-76C; MS (ES) m/z (relative intensity): 182 (M+H)+ (100).

Reference： [1]Patent: WO2007/146116,2007,A2 .Location in patent: Page/Page column 27

5
[ 452-83-5 ]
2-chloro-5-fluorobenzenediazonium tetrafluoroborate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With nitrosonium tetrafluoroborate; In acetonitrile; at 0℃; for 1h;	Nitrosonium tetrafluoroborate (802 mg, 6.87 mmol) was added to a solution of <strong>[452-83-5]2-chloro-5-fluoroaniline</strong> (1.00 g, 6.87 mmol) in acetonitrile (50 mL) at 0 C. The resulting mixture was stirred for 1 h, then diluted with ethyl ether (150 mL). The precipitate was filtered and air-dried to give 2-chloro-5-fluorobenzenediazonium tetrafluoroborate (1-1) as an off-white solid. 1H NMR (300 MHz, CD3OD) delta 8.66 (ddd, 1H, J=6.7, 2.1, 1.0 Hz), 8.16 (m1, 2H).
	With nitrosonium tetrafluoroborate; In acetonitrile; at 0℃; for 1h;	[NITROSONIUM] tetrafluoroborate (802 mg, 6.87 mmol) was added to a solution of <strong>[452-83-5]2-chloro-5-fluoroaniline</strong> (1.00 g, 6.87 mmol) in acetonitrile (50 [ML)] at [0C.] The resulting mixture was stirred for 1 hour, then diluted with ethyl ether (150 [ML).] The precipitate was filtered and air-dried to give 2-chloro-5- fluorobenzenediazonium tetrafluoroborate (1-1) as an off-white solid. lH NMR (300 MHz, CD30D) [8] 8.66 (ddd, 1H, [J =] 6.7, 2.1, 1.0 Hz), 8.16 (m, 2H).

Reference： [1]Patent: US2006/135594,2006,A1 .Location in patent: Page/Page column 31
[2]Patent: WO2003/105855,2003,A1 .Location in patent: Page 136

6
[ 345-17-5 ]
[ 452-83-5 ]

Yield	Reaction Conditions	Operation in experiment
84.5%	With tin(ll) chloride; In ethanol; at 70℃; for 0.5h;	A mixture of 0.17 g (1 mmol) of <strong>[345-17-5]2-chloro-5-fluoronitrobenzene</strong>, 1.13 g (5 mmol) of tin (II) chloride dihydrate and 10 ml of EtOH was stirred at 70C for 0.5 hours. After cooling to room temperature, the mixture was poured into H2O (30 ml), alkalinized with 10% Na2CO3 and extracted with CH2Cl2. The organic layer was dried (Na2SO4) and evaporated to dryness to give 0.12 g (84.5%) of the desired compound. 1H-NMR (CDCl3, delta): 4.16 (s, 2H, NH2), 6.51-6.77 (m, 2H, phenyl CHs), 7.09-7.21 (m, 1H, phenyl CH).

Reference： [1]Patent: EP1200406,2004,B1 .Location in patent: Page 14
[2]Green Chemistry,2012,vol. 14,p. 3164 - 3174,11

7
[ 666262-40-4 ]
[ 452-83-5 ]
[ 666263-11-2 ]

Yield	Reaction Conditions	Operation in experiment
	In 1,4-dioxane; at 100℃; for 18h;	2-Chloro-4-trifluoromethyl-pyrimidine-5-carboxylic acid cyclopentylmethyl-amide (100mg Example 183a), <strong>[452-83-5]2-chloro-5-fluoroaniline</strong> (ex-Fluorochem, 237mg), and 1,4-dioxan (1 ml) were stirred at 100C under nitrogen for 18h. The cooled reaction mixture was evaporated in vacuo, treated with ethyl acetate (5 ml), washed with aqueous 2M hydrochloric acid (2 x 3ml), followed by water (2x3 ml), and dried (Na2SO4). The solution was evaporated in vacuo and the residue purified by mass directed autopreparative purification to give the title compound (35mg). NMR 8 (CDC13) 1.2-1. 35 (2H, m), 1.53-1. 76 (>4H, m + H20), 1.78-1. 90 (2H, m), 2. 17 (1H, q), 3.41 (2H, dd), 5.9 (1H, brt), 7.0-7. 11 (2H, m), 7.65-7. 7 (1H, m) 8.56 (1H, dd), 8.79 (1H, s). LC/MS t = 3.67 min, Molecular ion observed [MH 417 consistent with the molecular formula C18H17ClF4N4O.
	In 1,4-dioxane; at 100℃; for 18h;Under nitrogen;	[2-CHLORO-4-TRIFLUOROMETHYL-PYRIMIDINE-5-CARBOXYLIC] acid cyclopentylmethyl-amide [(100MG] Example 183a), <strong>[452-83-5]2-chloro-5-fluoroaniline</strong> (ex-Fluorochem, 237mg), and 1,4-dioxan [(1] ml) were stirred at [100C] under nitrogen for 18h. The cooled reaction mixture was evaporated in vacuo, treated with ethyl acetate (5 ml), washed with aqueous 2M hydrochloric acid (2 x [3ML),] followed by water (2x3 ml), and dried [(NA2SO4).] The solution was evaporated in vacuo and the residue purified by mass directed autopreparative purification to give the title compound (35mg). NMR 8 [(CDCL3)] 1.2-1. 35 (2H, m), 1.53-1. 76 (>4H, [M] + H20), 1.78-1. 90 (2H, m), 2.17 [(1H,] [Q),] 3.41 (2H, dd), 5.9 [(1H,] brt), 7.0-7. 11 (2H, m), 7.65-7. 7 [(1H,] m) 8.56 [(1H,] dd), 8.79 [(1H,] s). LC/MS t = 3.67 min, Molecular ion observed [MH+] 417 consistent with the molecular formula C18H17ClF4N4O

Reference： [1]Patent: WO2005/74939,2005,A1 .Location in patent: Page/Page column 98
[2]Patent: WO2004/18433,2004,A1 .Location in patent: Page 113-114

Yield	Reaction Conditions	Operation in experiment
80%		Example 17 Analogously to Example 5, starting from 2-chloro-5-fluoroaniline, 2-chloro-5-fluorocinnamic acid was prepared in a yield of 80% of theory. The melting point of this cinnamic acid was 182 C. and the 1H-NMR spectrum showed characteristic absorptions at 6.6 ppm (d), 7.25 ppm (m), 7.5 ppm (m) and 7.75 (m), recorded in DMSO.

9
[ 452-83-5 ]
[ 82875-86-3 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sulfur dioxide; copper(II) chloride; sodium nitrite; In water; acetic acid; ethyl acetate;	a) 2-Chloro-5-fluorobenzenesulfonyl chloride 5 g (34.3 mM) of <strong>[452-83-5]2-chloro-5-fluoroaniline</strong> were slowly added to a solution of 17 ml of concentrated hydrochloric acid solution and 11 ml of water at 0 C. The reaction mixture is stirred at 0 C. for 1 hour. Addition of 2.49 g (36.1 mM) of NaNO2 in 6 ml of H2O is followed by stirring the mixture at 0 C. for 15 minutes and then adding to a solution of 692 mg (5.15 mM) of sulfur dioxide and copper(II) chloride in 10 ml of acetic acid. The reactants were stirred at 0 C. for 15 minutes and then at room temperature for a further 15 minutes. The reaction mixture is extracted with EtOAc. The organic phase is concentrated, dissolved in EtOAc, washed with 1N NaHCO3 solution, dried over MgSO4 and concentrated. 7.86 g of the desired sulfonyl chloride are obtained as a yellow oil.

Reference： [1]Patent: US2007/197539,2007,A1
[2]Patent: WO2006/24390,2006,A1 .Location in patent: Page/Page column 39-40

10
[ 452-83-5 ]
[ 372-31-6 ]
[ 917251-94-6 ]

Yield	Reaction Conditions	Operation in experiment
51%	With polyphosphoric acid; at 100 - 150℃; for 18h;	A solution of ethyl 4,4,4-trifluoroacetoacetate (commercially available, 4 mL, 27.3 mmol, 1.05 eq.) in polyphosphoric acid (22 mL) was heated to 100 C. <strong>[452-83-5]2-chloro-5-fluoroaniline</strong> (3.78 g, 26.0 mmol, 1 eq.) was added slowly to the stirred hot solution. The resulting reaction mixture was further heated to 150 C. and then stirred at that temperature overnight (approximately 18 hours). The reaction was cooled to room temperature and water was added carefully. The resulting light brown precipitate was collected by vacuum filtration, washed with water and dissolved in ethyl acetate. The ethyl acetate solution was washed with brine, dried over anhydrous MgSO4 and concentrated on a rotary evaporator. The crude product was purified by flash chromatography on silica gel using hexane/ethyl acetate to give 3.54 g (51% yield) of the desired product as an off-white solid; MP=141-142; MS (ES) m/z (relative intensity): 266 (M+H)+ (100).
51%	With PPA; at 100 - 150℃; for 18h;	A solution of ethyl 4,4,4-trifluoroacetoacetate (commercially available, 4 mL, 27.3 mmol, 1.05 eq.) in polyphosphoric acid (22 mL) was heated to 1000C. 2-chloro-5- fluoroaniline (3.78 g, 26.0 mmol, 1 eq.) was added slowly to the stirred hot solution. The resulting reaction mixture was further heated to 1500C and then stirred at that temperature overnight (approximately 18 hours). The reaction was cooled to room temperature and water was added carefully. The resulting light brown precipitate was collected by vacuum filtration, washed with water and dissolved in ethyl acetate. The ethyl acetate solution was washed with brine, dried over anhydrous MgSO4 and concentrated on a rotary evaporator. The crude product was purified by flash chromatography on silica gel <n="81"/>using hexane/ethyl acetate to give 3.54 g (51% yield) of the desired product as an off- white solid; MP = 141-142; MS (ES) m/z (relative intensity): 266 (M+H)+ (100).

Reference： [1]Patent: US2007/27160,2007,A1 .Location in patent: Page/Page column 60-61
[2]Patent: WO2007/146072,2007,A2 .Location in patent: Page/Page column 79-80

11
[ 452-83-5 ]
[ 56-81-5 ]
[ 917251-76-4 ]

Yield	Reaction Conditions	Operation in experiment
		Step 1: 5-Fluoro-8 chloroquinoline To a mixture of (5.0 g) <strong>[452-83-5]2-chloro-5-fluoroaniline</strong> (commercially available, 6.0 g), glycerol (6.0 g) and m-nitrobenzene sulfonic acid sodium salt (11.0 g), was added 20 mL of 70% sulfuric acid dropwise. The reaction temperature was raised to 140 C. for 2 h. The mixture was then cooled, poured on ice water and filtered through Celite. The filtrate was neutralized with NaOH and extracted with CH2Cl2. The combined organic layers were dried over anhydrous MgSO4 and concentrated on a rotary evaporator. The crude product was purified by flash chromatography on silica gel using 100% CH2Cl2 to give 3.7 g of the desired product of a yellow solid; MP=74-76 C.; MS (ES) m/z (relative intensity): 182 (M+H)+ (100).
		To a mixture of (5.0 g) <strong>[452-83-5]2-chloro-5-fluoroaniline</strong> (commercially available, 6.0 g), glycerol (6.0 g) and m-nitrobenzene sulfonic acid sodium salt (11.0 g), was added 20 ml of 70% sulfuric acid dropwise. The reaction temperature was raised to 140 C. for 2 hr. The mixture was then cooled, poured on ice water and filtered through celite. The filtrate was neutralized with NaOH and extracted with CH2Cl2. The combined organic layers were dried over anhydrous MgSO4 and concentrated on a rotary evaporator. The crude product was purified by flash chromatography on silica gel using 100% CH2Cl2 to give 3.7 g of the desired product of a yellow solid; MP=74-76 C.; MS (ES) m/z (relative intensity): 182 (M+H)+ (100).

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 4066 - 4084
[2]Patent: US2007/299083,2007,A1 .Location in patent: Page/Page column 14
[3]Patent: US2007/27160,2007,A1 .Location in patent: Page/Page column 46

12
[ 452-83-5 ]
ammonium thiocyanate [ No CAS ]
[ 701294-26-0 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In water; at 110℃; for 6h;Heating / reflux;	A mixture of <strong>[452-83-5]2-chloro-5-fluoroaniline</strong> Na (2.0 g, 13.7 mmol) and 1.7 g of NH4SCN in 4N-HCI (20 ml.) was heated to reflux at 1 10C for 6 hours. After cooling, it was treated with H2O to form a solid, followed by desiccation in vacuo to give thiourea Ilia (870 mg, 4.3 mmol). A mixture of Ilia (870 mg, 4.3 mmol), CICH2CO2H (400 mg), and AcONa (350 mg) in AcOH (5 ml.) was heated to reflux at 110 C0 for 4 h. The mixture was poured onto water and the formed solid was isolated by filtration. It was washed with MeOH to give imino thiazolidinone IVa (456 mg, 1.9 mmol). A mixture of IVa (98 mg, 0.4 mmol), aldehyde Va (60 mg, 0.4 mmol), AcONa (100 mg) in AcOH (2 ml.) was heated to reflux at 120 degree for 48 hours. After cooling, a small portion of water was added until the solid forms. It was filtered and washed with MeOH, followed by desiccation in vacuo to afford a target product Ia (61 mg, 0.16 mmol). <n="65"/>1HNMR: (DMSO-Cl6) delta 3.21 (t, 2H), 4.58 (t, 2H), 6.87 (d, 1 H), 7.06 (sbr, 2H), 7.30 (d, 1H), 7.39 (s, 1H), 7.58 (sbr, 2H), 12.60 (sbr, 1H) : LC/MS: m/z 375 (M+1), 377 (M+3)

Reference： [1]Patent: WO2007/103754,2007,A2 .Location in patent: Page/Page column 63-64

13
[ 106-38-7 ]
[ 452-83-5 ]
C₁₃H₁₁ClFN [ No CAS ]
[ 1041143-57-0 ]

Reference： [1]Tetrahedron,2008,vol. 64,p. 6038 - 6050

14
[ 95-46-5 ]
[ 452-83-5 ]
C₁₃H₁₁ClFN [ No CAS ]
[ 1041143-53-6 ]
[ 1041155-26-3 ]

Reference： [1]Tetrahedron,2008,vol. 64,p. 6038 - 6050

15
[ 90-11-9 ]
[ 452-83-5 ]
[ 1041143-65-0 ]

Reference： [1]Tetrahedron,2008,vol. 64,p. 6038 - 6050

16
[ 556-96-7 ]
[ 452-83-5 ]
[ 1041144-06-2 ]
[ 1041143-61-6 ]

Reference： [1]Tetrahedron,2008,vol. 64,p. 6038 - 6050

17
[ 556-96-7 ]
[ 452-83-5 ]
[ 1041144-06-2 ]

Reference： [1]Tetrahedron,2008,vol. 64,p. 6038 - 6050

18
[ 452-83-5 ]
[ 109608-77-7 ]
[ 1000049-67-1 ]

Yield	Reaction Conditions	Operation in experiment
53%		(62a) [2-(2-Chloro-5-fluorophenylamino)-1,1-dimethylethyl]carbamic acid t-butyl ester 10.0 g of sodium triacetoxyborohydride (47.2 mmol) was added to a solution of 6.0 g of (1,1-dimethyl-2-oxoethyl)carbamic acid t-butyl ester obtained in Reference Example 3 (32.0 mmol), 4.6 g of 2-chloro-5-fluoroaniline (32.0 mmol) and 1.8 ml of acetic acid (32.0 mmol) in methylene chloride (320 ml) under ice-cooling, and the mixture was stirred at room temperature for 16 hours. A saturated sodium bicarbonate aqueous solution was added to the reaction mixture, followed by extraction with methylene chloride. Then, the organic layer was washed with brine and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate = 5/1) to obtain 5.36 g of the title compound (yield: 53%). Colorless solid. 1H NMR spectrum (CDCl3, 400 MHz), delta: 7.16-7.13 (m, 1H), 6.48-6.37 (m, 1H), 6.31-6.26 (m, 1H), 4.78 (br s, 1H), 4.52 (br s, 1H), 3.35 (br d, 2H, J = 5.9 Hz), 1.43 (s, 9H), 1.35 (s, 6H).

Reference： [1]Patent: EP2036896,2009,A1 .Location in patent: Page/Page column 105
[2]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4561 - 4566

19
[ 576-83-0 ]
[ 452-83-5 ]
[ 1188930-02-0 ]

Reference： [1]Chemical Communications,2009,p. 4832 - 4834

20
[ 400-36-2 ]
[ 452-83-5 ]
[ 917251-94-6 ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 4066 - 4084

21
[ 98946-18-0 ]
[ 452-83-5 ]
[ 1236306-15-2 ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 10706 - 10716

22
[ 2039-88-5 ]
[ 452-83-5 ]
[ 1246225-22-8 ]

Yield	Reaction Conditions	Operation in experiment
53%	With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; DavePhos; In 1,4-dioxane; at 115℃; for 6h;Inert atmosphere;	General procedure: A mixture of 2-bromostyrene (549mg, 3.00mmol), the appropriate 2-chloroaniline derivative (3.00mmol), Pd(dba)3 (68mg, 0.075mmol), DavePhos (79mg, 0.20mmol), and NaOtBu (864mg, 9.00mmol) in dry 1,4-dioxane (10mL) was stirred under a N2 atmosphere at 115C for 6h. After it had been cooled down to rt, EtOAc (150mL) was added. The mixture was washed with water (5×150mL) and subsequently with brine (150mL). The organic phase was separated and dried over MgSO4. After evaporation of the solvent, the residue was submitted to column chromatography (SiO2, eluent: petroleum ether/EtOAc 20:1). The yellow fraction was collected, and evaporation of the eluent in vacuo gave the desired product.

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 14048 - 14051
[2]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 1077 - 1088

23
[ 2039-88-5 ]
[ 452-83-5 ]
[ 1246225-48-8 ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 14048 - 14051

24
[ 452-83-5 ]
[ 139469-06-0 ]
[ 1246225-23-9 ]

Reference： [1]Journal of the American Chemical Society,2010,vol. 132,p. 14048 - 14051

25
[ 452-83-5 ]
[ 1000047-67-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4561 - 4566

26
[ 452-83-5 ]
[ 1000049-80-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4561 - 4566

27
[ 452-83-5 ]
[ 1000049-71-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4561 - 4566

28
[ 452-83-5 ]
[ 1000049-75-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4561 - 4566

29
[ 321-14-2 ]
[ 452-83-5 ]
[ 1417658-22-0 ]

Yield	Reaction Conditions	Operation in experiment
26%	With pyridine; phosphorus trichloride; In toluene; for 12h;Inert atmosphere; Reflux;	General procedure: The salicylic acid (1.2 equiv) was added to a mixture of toluene (0.3 M), aniline (1.0 equiv), phosphorus trichloride (1.1 equiv), and pyridine (0.05 equiv) in a Radley?s Carousel reaction tube (modified from Itai et al.20). The mixture was refluxed under nitrogen for 12 h then cooled to room temperature. Aqueous sodium bicarbonate was added dropwise to attain pH 6-7. The resultant mixture was extracted with EtOAc. The organic extracts were combined, dried (MgSO4), and concentrated under vacuum. After chromatography (1:10 EtOAc:Hex) compounds were recrystallized (EtOAc/Hex).

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 114 - 126

30
[ 13321-74-9 ]
[ 452-83-5 ]
[ 1432270-46-6 ]

Yield	Reaction Conditions	Operation in experiment
46%	With palladium diacetate; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 160℃; for 3h;Inert atmosphere; Microwave irradiation;	General procedure: NaOt-Bu (0.240 g, 2.5 mmol), Pd(OAc)2 (0.006 g, 0.025 mmol) and [HPt-Bu3][BF4] (0.010 g, 0.035 mmol) were suspended in toluene (3 ml) in a 5 ml microwave vial. The appropriate 2-chloroaniline (0.50 mmol) and aryl bromide (0.50 mmol) were then added and the vial sealed. The reaction was then heated in the microwave reactor at 160 C for 3 h, allowed to cool, and then quenched by addition of aqueous HCl (2 M, 3 ml). The organic phase was extracted with CH2Cl2 (2×20 ml), dried (MgSO4), then filtered and the solvent removed under reduced pressure. The crude product mixture was then subjected to column chromatography (SiO2).

Reference： [1]Tetrahedron,2013,vol. 69,p. 4389 - 4394

31
[ 452-83-5 ]
[ 103323-61-1 ]
[ 1432270-60-4 ]

Yield	Reaction Conditions	Operation in experiment
64%	With palladium diacetate; sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; at 160℃; for 3h;Inert atmosphere; Microwave irradiation;	General procedure: NaOt-Bu (0.240 g, 2.5 mmol), Pd(OAc)2 (0.006 g, 0.025 mmol) and [HPt-Bu3][BF4] (0.010 g, 0.035 mmol) were suspended in toluene (3 ml) in a 5 ml microwave vial. The appropriate 2-chloroaniline (0.50 mmol) and aryl bromide (0.50 mmol) were then added and the vial sealed. The reaction was then heated in the microwave reactor at 160 C for 3 h, allowed to cool, and then quenched by addition of aqueous HCl (2 M, 3 ml). The organic phase was extracted with CH2Cl2 (2×20 ml), dried (MgSO4), then filtered and the solvent removed under reduced pressure. The crude product mixture was then subjected to column chromatography (SiO2).

Reference： [1]Tetrahedron,2013,vol. 69,p. 4389 - 4394

32
[ 452-83-5 ]
7-fluoropyrido[1,2-a]benzimidazole [ No CAS ]

Reference： [1]Tetrahedron,2013,vol. 69,p. 5487 - 5494

33
[ 452-83-5 ]
2-halopyridine [ No CAS ]
[ 1439922-54-9 ]

Yield	Reaction Conditions	Operation in experiment
86%	With palladium diacetate; caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 100℃; for 14h;Inert atmosphere;	General procedure: A mixture of aniline (3mmol), 2-halopyridine (3mmol), Cs2CO3 (9mmol), Pd(OAc)2 (0.12mmol), and BINAP (0.12mmol) in toluene (5mL) under an argon atmosphere was stirred at 100C for 14h. After cooling, the reaction mixture was diluted with ethyl acetate and filtered. The filtrate was evaporated and the residue purified by column chromatography on silica gel eluting with petroleum ether (bp 60-80C)/ethyl acetate to give the desired products.

Reference： [1]Tetrahedron,2013,vol. 69,p. 5487 - 5494

34
[ 452-83-5 ]
[ 460-00-4 ]
2-chloro-5-fluoro-N-(4-fluorophenyl)aniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate; In toluene; at 110℃; for 5h;Inert atmosphere;	Preparation 47 2-Chloro-5-fluoro-N-(4-fluorophenyl)aniline A round bottom flask was charged with 1-bromo-4-fluorobenzene (4.809 g, 27.5 mmol), <strong>[452-83-5]2-chloro-5-fluoroaniline</strong> (4.000 g, 27.5 mmol), Xantphos (0.636 g, 1.1 mmol), anhydrous toluene (100 mL), and sodium tert-butoxide (3.961 g, 41.2 mmol). The mixture was degassed and filled with argon, and then tris(dibenzylideneacetone)dipalladium(0) (0.755 g, 0.8 mmol) was added and the reaction was stirred under argon at 110 C. for 5 hrs. After cooling to room temperature, the mixture was treated with water and extracted with diethyl ether. The organic layer was washed with saturated aqueous sodium chloride, dried (anhydrous magnesium sulfate), filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (0-20% ethyl acetate/hexanes) to afford the product as a colorless oil (5.75 g, 87%). 1H NMR (300 MHz, CDCl3) delta 7.27 (dd, 1H, J=9.0, 5.4 Hz), 7.23-7.03 (m, 4H), 6.71 (dd, 1H, J=10.8, 2.4 Hz), 6.47 (td, 1H, J=8.1, 3.0 Hz), 6.09 (br s, 1H).

Reference： [1]Patent: US2013/303524,2013,A1 .Location in patent: Paragraph 0331-0332

35
[ 452-83-5 ]
2,6-difluoro-9H-carbazole [ No CAS ]

Reference： [1]Patent: US2013/303524,2013,A1

36
[ 452-83-5 ]
2,6-difluoro-9-(oxiran-2-ylmethyl)-9H-carbazole [ No CAS ]

Reference： [1]Patent: US2013/303524,2013,A1

37
[ 452-83-5 ]
[ 140-89-6 ]
5-fluoro-1,3-benzothiazole-2(3H)-thione [ No CAS ]