[ CAS No. 1996-44-7 ] {[proInfo.proName]}

Name: 1996-44-7|2,4-Difluorothiophenol|97%
Brand: Ambeed
SKU: A581830
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Quality Control of [ 1996-44-7 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1996-44-7 ]

SDS Specification

Alternatived Products of [ 1996-44-7 ]

Product Details of [ 1996-44-7 ]

CAS No. :	1996-44-7	MDL No. :	MFCD00203477
Formula :	C₆H₄F₂S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	BICHBFCGCJNCAT-UHFFFAOYSA-N
M.W :	146.16	Pubchem ID :	2737073
Synonyms :

Calculated chemistry of [ 1996-44-7 ]

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	33.61
TPSA :	38.8 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) :	-5.37 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.97
Log Po/w (XLOGP3) :	2.57
Log Po/w (WLOGP) :	3.09
Log Po/w (MLOGP) :	3.41
Log Po/w (SILICOS-IT) :	2.99
Consensus Log Po/w :	2.81

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.86
Solubility :	0.202 mg/ml ; 0.00138 mol/l
Class :	Soluble
Log S (Ali) :	-3.03
Solubility :	0.135 mg/ml ; 0.000927 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.04
Solubility :	0.132 mg/ml ; 0.000904 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.28

Safety of [ 1996-44-7 ]

Signal Word:	Danger	Class:	3
Precautionary Statements:	P210-P233-P240-P241+P242+P243-P261-P264-P270-P271-P280-P301+P312+P330-P302+P352+P312+P362+P364-P304+P340+P312-P305+P351+P338+P337+P313-P403+P235-P501	UN#:	1993
Hazard Statements:	H225-H302+H312+H332-H315-H319	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 1996-44-7 ]

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

Upstream synthesis route of [ 1996-44-7 ]
Downstream synthetic route of [ 1996-44-7 ]

[ 1996-44-7 ] Synthesis Path-Upstream 1~3

1
[ 1996-44-7 ]
[ 13918-92-8 ]

Reference： [1] Green Chemistry, 2017, vol. 19, # 9, p. 2286 - 2295

2
[ 1996-44-7 ]
[ 13656-60-5 ]

Reference： [1] Organic and Biomolecular Chemistry, 2016, vol. 14, # 29, p. 6951 - 6954

3
[ 42456-75-7 ]
[ 1996-44-7 ]
[ 1247819-59-5 ]

Yield	Reaction Conditions	Operation in experiment
39%	With sodium methylate In methanol	2-Acetyl-5-chlorothiophene (4.00 g, 24.8 mmol) was added potionwise to fuming nitric acid (24 mL) cooled in an ice-bath. The reaction mixture was then stirred at ambient temperature for 30 minutes and poured into 200 mL ice water. Then solid was precipitated and extracted with ethyl ether. The organic phase was dried, filetered and concentrated in vacuo to get crude product 1-(5-chloro-4-nitrothiophen-2-yl)ethanone (4.50 g) as yellow solid without further purification2,4-difluorobenzenethiol (4.30 g, 29.4 mmol) was added to a solution of sodium methanol (1.40 g, 26.3 mmol) in methanol (250 mL). The mixture was stirred at ambient temperature for 20 minuters. Then 1-(5-chloro-4-nitrothiophen-2-yl)ethanone (5.50 g, crude product) was added and the mixture was stirred overnight. Water (250 mL) was added and the solid which formed collected by filtration and dried under vacuum at 40^oC. The product was recrystallized twice from acetonitrile to give a white solid (3.30 g, 39percent). ¹H NMR (300 MHz, DMSO) δ 8.50, 8.00, 7.97, 7.95, 7.92, 7.71, 7.70, 7.68, 7.67, 7.65, 7.64, 7.43, 7.40, 7.37, 2.50.

Reference： [1] Medicinal Chemistry letters, 2012, vol. 3, # 10, p. 789 - 792,4
[2] ACS Medicinal Chemistry Letters, 2012, vol. 3, # 10, p. 789 - 792
[3] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 4, p. 845 - 849

[ 1996-44-7 ] Synthesis Path-Downstream 1~88

1
[ 367-25-9 ]
[ 1996-44-7 ]

Reference： [1]Chemische Berichte,1964,vol. 97,p. 735 - 740

2
[ 1722-10-7 ]
[ 1996-44-7 ]
3-(2,4-difluoro-phenylsulfanyl)-6-methoxy-pyridazine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 6326 - 6339

3
[ 4923-60-8 ]
[ 1996-44-7 ]
2,3-bis-(2,4-difluoro-phenylsulfanyl)-5-hydroxy-[1,4]naphthoquinone [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2005,vol. 40,p. 438 - 444

4
[ 526-86-3 ]
[ 1996-44-7 ]
[ 928027-52-5 ]

Reference： [1]Synthetic Communications,2006,vol. 36,p. 3319 - 3328

5
6-chloro-2-(4-chloro-2-methyl-phenyl)-2H-pyridazin-3-one [ No CAS ]
[ 1996-44-7 ]
2-(4-chloro-2-methyl-phenyl)-6-(2,4-difluoro-phenylsulfanyl)-2H-pyridazin-3-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5809 - 5813

6
[ 1996-44-7 ]
S-methyl O-(4-nitrophenyl) thiocarbonate [ No CAS ]
C₈H₆F₂OS₂ [ No CAS ]
[ 14609-74-6 ]

Reference： [1]Journal of Physical Organic Chemistry,2007,vol. 20,p. 533 - 538

7
[ 6132-46-3 ]
[ 1996-44-7 ]
C₈H₆F₂OS₂ [ No CAS ]
[ 20350-26-9 ]

Reference： [1]Journal of Physical Organic Chemistry,2007,vol. 20,p. 533 - 538

8
[ 1996-44-7 ]
[ 209412-06-6 ]
[ 209412-22-6 ]

Reference： [1]Journal of Organic Chemistry,2009,vol. 74,p. 8336 - 8342
[2]Tetrahedron Letters,2009,vol. 50,p. 3661 - 3664
[3]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5107 - 5110

9
[ 1996-44-7 ]
3-(2,4-difluoro-benzenesulfonyl)-6-methoxy-pyridazine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 6326 - 6339

10
[ 1996-44-7 ]
6-(2,4-difluoro-benzenesulfonyl)-2H-pyridazin-3-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 6326 - 6339

11
[ 1996-44-7 ]
5-(2,4-difluorobenzothiolate)-2-furfuraldehyde thiosemicarbazone [ No CAS ]

Reference： [1]Synthesis,2005,p. 899 - 902

12
[ 1996-44-7 ]
[ 212078-66-5 ]

Reference： [1]Bioorganic and medicinal chemistry,2004,vol. 12,p. 2251 - 2273

13
[ 1996-44-7 ]
4-[(E)-3-(5,7-difluoro-3-methylbenzo[b]thiophen-2-yl)-2-propen-1-yl]-1H-imidazole [ No CAS ]

Reference： [1]Bioorganic and medicinal chemistry,2004,vol. 12,p. 2251 - 2273
[2]Bioorganic and medicinal chemistry,2004,vol. 12,p. 2251 - 2273

14
[ 1996-44-7 ]
1-(5,7-difluoro-3-methyl-benzo[b]thiophen-2-yl)-3-(1H-imidazol-4-yl)-propan-1-ol [ No CAS ]

Reference： [1]Bioorganic and medicinal chemistry,2004,vol. 12,p. 2251 - 2273

15
[ 1996-44-7 ]
[ 212078-67-6 ]

Reference： [1]Bioorganic and medicinal chemistry,2004,vol. 12,p. 2251 - 2273

16
[ 1996-44-7 ]
3-(2,4-difluoro-phenylsulfanyl)-6-methanesulfonyl-1H-indole-2-carbonitrile [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 4741 - 4745

17
[ 1996-44-7 ]
3-(2,4-difluoro-phenylsulfanyl)-6-methanesulfonyl-1H-indole-2-carbonyl chloride [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 4741 - 4745

18
[ 1996-44-7 ]
[ 507272-18-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 4741 - 4745

19
[ 1996-44-7 ]
3-(2,4-difluoro-phenylsulfanyl)-6-methanesulfonyl-1H-indole-2-carboxylic acid methylamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 4741 - 4745

20
[ 1996-44-7 ]
[ 507271-76-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 4741 - 4745

21
[ 367-27-1 ]
[ 1996-44-7 ]

Reference： [1]Synthetic Communications,1995,vol. 25,p. 2791 - 2806

22
[ 1996-44-7 ]
[ 158205-23-3 ]

Reference： [1]Synthetic Communications,1995,vol. 25,p. 2791 - 2806

23
[ 1996-44-7 ]
[ 158205-05-1 ]

Reference： [1]Synthetic Communications,1995,vol. 25,p. 2791 - 2806

24
[ 1996-44-7 ]
[ 170456-58-3 ]

Reference： [1]Synthetic Communications,1995,vol. 25,p. 2791 - 2806

25
[ 170456-59-4 ]
[ 1996-44-7 ]

Reference： [1]Synthetic Communications,1995,vol. 25,p. 2791 - 2806

26
[ 632628-09-2 ]
[ 1996-44-7 ]
[ 632628-10-5 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; for 12h;	To a stirred, deoxygenated, solution ofcompound 4 (4. 0g, 9.90mmoles) in [LOML] of dioxane was added <strong>[1996-44-7]2,4 difluor thiophenol</strong> (1.76g, [11. 80MMOLES).] Then [N,] [N-DIISOPROPYLETHYLAMINE] (2. [55G,] 19. [73MMOLES)] was added and the reaction was heated under argon at [100C] overnight. After 12h, TLC showed complete consumption of starting material. The reaction mixture was diluted with 20mL of ethylacetate and lOmL of 5% sodium hydroxide solution. The organic phase was separated and washed with lOmL of brine twice, dried over sodium sulphate and concentrated to give a viscous oil. The residue was purified by flash column chromatography (gradient: 0-40% ethyl acetate in hexanes) and product 5 was obtained. 1H NMR [(CDCI,] 500 MHz, ppm) 7.88 [(1H,] s); 7,5 [(1H,] m); 7.1 (2H, d, 8.5 Hz); 6.8 (2H, d, 8.5 Hz); 6.83 [(1H,] m); 6.70 [(1H,] m); 3.85 (3H, s); 3.80 (2H, s); 3.55 (2H, bs). MS: [M+H] = 529

Reference： [1]Patent: WO2003/103590,2003,A2 .Location in patent: Page 28

27
[ 598298-13-6 ]
[ 1996-44-7 ]
[6-(2,4-Difluorophenylsulfanyl)thieno[2,3-d]pyrimidin-2-yl]-(tetrahydropyran-4-yl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		<strong>[1996-44-7]2,4-Difluorobenzenethiol</strong> (0.35 mL, 10.8 eq) was added to 6-iodo-thieno[2,3-d]pyrimidin-2-yl)-(tetrahydropyran-4-yl)-amine (100 mg, 0.277 mmol), and the resulting mixture was stirred overnight at room temperature. The reaction mixture was then heated 100 C. with stirring for 5 hours, after which 1-methyl-2-pyrolidinone (0.2 mL) was added followed by potassium carbonate (415 mg, 10.8 eq). The resulting mixture was heated with stirring to 150 C. for an additional 5 hours. The reaction mixture was then cooled to room temperature and diluted with ethyl acetate (35 mL)/water (20 mL). The layers were separated. The organic layer was washed with successively with water (3×20 mL) and brine (1×20 mL), dried over magnesium sulfate, filtered and concentrated to yield a crude product (452 mg), which was purified by Preparative Thin Layer Chromatography eluting on four (20×40 cm, 1000 muM) silica gel plates with 55% ethyl acetate in hexanes to afford the title compound (16 mg) as an off-white powder (M+H)+=380.

Reference： [1]Patent: US2003/207900,2003,A1 .Location in patent: Page/Page column 21

28
[ 1996-44-7 ]
[ 876372-94-0 ]

Yield	Reaction Conditions	Operation in experiment
92%	With aluminum oxide; In dimethyl sulfoxide; at 40℃; for 0.5h;	2,4-Difluorobenzene thiol (1.13 ml, 10.0 mmol) was stirred in 2 ml DMSO with ~ 50 mg of neutral alumina at 40 0C for 30 minutes. The reaction was filtered, diluted with 150 ml of ethyl acetate and washed 5 times with 75 ml of water. The organic layer was dried over MgSO4, filtered, and concentrated with a nitrogen stream in the hood to obtain a yellow oil (1.33 g, 92% yield). 1H NMR (400 MHz, DMF-d7) delta 7.76 (dt, J= 8.7, 6.2 Hz, 2H), 7.44 (dt, J= 9.5, 2.6 Hz, 2H), 7.24 (ddt, J= 8.5, 2.6, 1.0, 2H); LC/MS, tr = 3.60 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50 0C), ES-MS m/z 290 (M+H).
92%	With aluminum oxide; In dimethyl sulfoxide; at 40℃; for 0.5h;	2,4-DifIuorobenzene thiol (1.13 ml, 10.0 mmol) was stirred in 2 ml DMSO with ~ 50mg of neutral alumina at 40 C for 30 minutes. The reaction was filtered, diluted with 150 ml ofethyl acetate and washed 5 times with 75 ml of water. The organic layer was dried over MgSO4,filtered, and concentrated with a nitrogen stream in the hood to obtain a yellow oil (1.33 g, 92%yield). 1H NMR (400 MHz, DMF-cW 8 7.76 (dt, J= 8.7, 6.2 Hz, 2H), 7.44 (dt, J= 9.5, 2;6 Hz, 2H),7.24 (ddt, J= 8.5, 2.6,1.0, 2H); LC/MS, tr = 3.60 minutes (5 to 95% acetonitrile/water over 5minutes at 1 ml/min, at 254 nm, at 50 C), ES-MS m/z290 (M+H).

Reference： [1]Patent: WO2006/18735,2006,A2 .Location in patent: Page/Page column 69
[2]Patent: WO2006/18727,2006,A2 .Location in patent: Page/Page column 85
[3]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 469 - 473
[4]Tetrahedron,2010,vol. 66,p. 2823 - 2829

29
[ 434285-95-7 ]
[ 1996-44-7 ]
[ 534582-89-3 ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide;	Part D <strong>[1996-44-7]2,4-Difluorobenzenethiol</strong> (2 g, 13.7 mmol) was added to a suspension of sodium hydride (0.65 g of 60%, 16.5 mmol) in anhydrous N,N-dimethylformamide (30 mL). After the addition was complete the reaction mixture was allowed to stir at ambient temperature for about 30 minutes. 2-Butyl-1-(4-chlorobutyl)-1H-imidazo[4,5-c]quinoline-4-amine (4.5 g, 13.6 mmol) was added in a single portion. The reaction mixture was allowed to stir at ambient temperature for about 30 minutes; then it was poured into ice water and stirred. The aqueous layer was extracted with dichloromethane (575 mL). The combined organics were washed with water (3100 mL) and brine, and then concentrated under reduced pressure to provide 6.7 g of a solid. This material was recrystallized from ethanol. A portion (1.1 g) was dried in a heated vacuum oven to provide 2-butyl-1-{4-[(2,4-difluorophenyl)thio]butyl}-1H-imidazo[4,5-c]quinolin-4-amine as a solid, m.p. 122-126 C. Analysis: Calculated for C24H26F2N4S: %C, 65.43; %H, 5.95; %N, 12.72; Found: %C, 65.41; %H, 5.98; %N, 12.80. 1H NMR (300 MHz, DMSO-d6) delta 8.02 (d, J=7.5 Hz, 1H), 7.62 (d, J=7.2 Hz, 1H), 7.42 (m, 2H), 7.25 (m, 2H), 7.05 (t, J=6 Hz, 1H), 6.46 (s, 2H), 4.50 (t, J=7.5 Hz, 2H), 2.97 (t, J=6.6 Hz, 2H), 2.87 (t, J=7.2 Hz, 2H), 1.92 (quintet, J=7.8 Hz, 2H), 1.76 (quintet, J=7.8 Hz, 2H), 1.64 (quintet, J=7.5 Hz, 2H), 1.42 (sextet, J=7.5 Hz, 2H), 0.94 (t, J=7.2 Hz, 3H); MS (CI) m/e 441 (M+H)
		Part D <strong>[1996-44-7]2,4-Difluorobenzenethiol</strong> (2 g, 13.7 mmol) was added to a suspension of sodium hydride (0.65 g of 60%, 16.5 mmol) in anhydrous N,N-dimethylformamide (30 ML).. After the addition was complete the reaction mixture was allowed to stir at ambient temperature for about 30 minutes. 2-Butyl-1-(4-chlorobutyl)-1H-imidazo[4,5-c]quinoline-4-amine (4.5 g, 13.6 mmol) was added in a single portion.. The reaction mixture was allowed to stir at ambient temperature for about 30 minutes; then it was poured into ice water and stirred.. The aqueous layer was extracted with dichloromethane (575 ML).. The combined organics were washed with water (3100 ML) and brine, and then concentrated under reduced pressure to provide 6.7 g of a solid.. This material was recrystallized from ethanol.. A portion (1.1 g) was dried in a heated vacuum oven to provide 2-butyl-1-{4-[(2,4-difluorophenyl)thio]butyl}-1H-imidazo[4,5-c]quinolin-4-amine as a solid, m.p. 122-126 C. Analysis: Calculated for C24H26F2N4S: %C, 65.43; %H, 5.95; %N, 12.72; Found: %C, 65.41; %H, 5.98; %N, 12.80. 1H NMR (300 MHz, DMSO-d6) delta 8.02 (d, J=7.5 Hz, 1H), 7.62 (d, J=7.2 Hz, 1H), 7.42 (m, 2H), 7.25 (m, 2H), 7.05 (t, J=6 Hz, 1H), 6.46 (s, 2H), 4.50 (t, J=7.5 Hz, 2H), 2.97 (t, J=6.6 Hz, 2H), 2.87 (t, J=7.2 Hz, 2H), 1.92 (quintet, J=7.8 Hz, 2H), 1.76 (quintet, J=7.8 Hz, 2H), 1.64 (quintet, J=7.5 Hz, 2H), 1.42 (sextet, J=7.5 Hz, 2H), 0.94 (t, J=7.2 Hz, 3H); MS (CI) m/e 441 (M+H)

Reference： [1]Patent: US2003/100764,2003,A1
[2]Patent: US6667312,2003,B2 .Location in patent: Page column 63-64

30
[ 64495-43-8 ]
[ 1996-44-7 ]
5-(2,4-difluoro-phenylsulfanyl)-2-methanesulfonyl-6-methoxy-quinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80-90%		Step 4 A solution of 2-methanesulfonyl-6-methoxy-quinoline (237 mg, 1 mmole) and <strong>[1996-44-7]2,4-difluorobenzenethiol</strong> (296 mg,2 mmoles) was treated with PIFA (645 mg, 1. 5 mmoles) and stirred for 30 min. The solution was poured into dilute NaCl solution and extracted with ethyl acetate (EtOAc). The organic layer was dried (MgSO4) and evaporated. The resulting oil was crystallized to yield 5-(2,4-difluoro-phenylsulfanyl)-2-methanesulfonyl-6-methoxy-quinoline 101.; ([M+H]+)=382 The yield is typically 80-90%.

Reference： [1]Patent: US2002/82276,2002,A1

31
aqueous potassium hydroxide [ No CAS ]
[ 1996-44-7 ]
[ 158205-21-1 ]
[ 158205-22-2 ]

Yield	Reaction Conditions	Operation in experiment
81%	In pyridine;	Step 7 5-Nitro-6-(2,4-difluorophenylthio)-1-indanone ethylene ketal To a mixture of 5-nitro-6-bromo-1-indanone ethylene ketal (600 mg, 2.0 mmol) and <strong>[1996-44-7]2,4-difluorothiophenol</strong> (F. Klages and K. Bott Chem. Ber. 97,735 (1964)) (440 mg, 3.0 mmol) in pyridine (4.0 mL) was added a solution of 8M aqueous potassium hydroxide (375 muL, 3.0 mmol) at room temperature. The mixture was stirred for 2 h, diluted with water and extracted with ethyl acetate. The ethyl acetate extract was washed successively with 1M aqueous NaOH (2x),0.5M aqueous HCl (1x), brine, dried over anhydrous MgSO4 and concentrated in vacuo. Chromatography over silica gel and eluted with toluene: ethyl acetate (10:1) afforded the title compound (590 mg, 81%) as a pale yellow solid. 1 H NMR (CDCl3) delta8.12 (s,1H), 7.60 (m, 1H), 7.00 (m, 2H), 6.70 (s, 1H), 4.10-3.90 (m 4H), 2.95 (t, 2H), 2.30 (t, 2H).

Reference： [1]Patent: US5604260,1997,A

32
[ 923973-04-0 ]
[ 1996-44-7 ]
1-(2,6-dichloro-phenyl)-5-(2,4-difluoro-phenylsulfanyl)-3-methyl-pyrazolo[1,5-a]pyrimidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In 1-methyl-pyrrolidin-2-one; at 180℃; for 0.0833333h;Microwave irradiation;	EXAMPLE 6l-(2,6-Difluoro-phe?yl)-S-(2,4-difluoro-phenyIsuJfanyl)-3-methyl-pyrazoIo[l,5-a]pyriniidin-2-one:To a solution 5-chloro-l-(2,6-dichIoro-phenyl)-3-methyl-pyrazolo[l,5-a]pyrimidin-2-one (25 mg, 0.076 mmol) from step 9 of Example 4 in NMP (1.5 mL) were added <strong>[1996-44-7]2,4-difluorothiophenol</strong> (1 1 mg, 0.076 mmol), followed by CS2CO3 (25 mg, 0.076 mmol) in one portion each. The resulting mixture was irradiated in a microwave 180 0C for 5 min. The conversion was monitored by TLC. The microwave vessel was cooled down to room temperature, and rinsed into a seperatory funnel. It was extracted with ethyl acetate (3x 10 mL), washed with water (Ix 25mL), and brine (1x25 mL), dried over Na^SO^ It was filtered off and concentrated in vacuo to give the crude product that was purified by RP C- 18 column chromatography eluted with 20-60% CH3CN in water to afford l-(2,6-dichloro-phenyl)-5-(2,4- EPO <DP n="40"/>difluoro-phenylsulfanyl)-3-methyl-pyrazolo[l ,5-a]pyrimidin-2-one (6 mg) as a yellow solid. 1H NMR (CD3OD) delta: 7.81-7.80 (d, IH), 7.75-7.64 (m, 4H), 7.26-7.13 (m, 2H), 6.35-6.32 (d, IH), 1.87 (s, 3H); LCMS: 440.09 (M+l)+.

Reference： [1]Patent: WO2007/15866,2007,A2 .Location in patent: Page/Page column 38-39

33
[ 940891-92-9 ]
[ 1996-44-7 ]
5-(2,6-difluorophenyl)-2-[(2,4-difluorophenyl)thio]-6H-pyrido[1,2-b]pyridazin-6-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In tetrahydrofuran; for 0.166667h;	To a solution of NaH (20 mg, 0.83 mmol) and <strong>[1996-44-7]2,4-difluorobenzenethiol</strong> (74 mg, 0.51 mmol), in THF 2 mL was added 2-chloro-5-(2,6-difluorophenyl)-6H-pyrido[1,2-b]pyridazin-6-one (50 mg, 0.17 mmol) as a solution in THF (1 mL). The reaction was complete in 10 min and concentrated in vacuo. The crude residue was purified via silica gel chromatography (EtOAc/CH2Cl2/MeOH) to yield the title compound. 1H NMR (CD3OD): 8.28 (d, 1H), 7.76 (m, 1H), 7.55 (m, 1H), 7.36 (d, 1H), 7.25 (m, 1H), 7.08-7.18 (m, 4H), 6.82 (d, 1H). MS(ES): 402.9 (M+H).

Reference： [1]Patent: US2007/129372,2007,A1 .Location in patent: Page/Page column 21
[2]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 411 - 416

34
[ 33821-94-2 ]
[ 1996-44-7 ]
[ 915771-67-4 ]

Yield	Reaction Conditions	Operation in experiment
84%		Intermediate 26: 2-[3-(2,4-difluorophenyl)sulfanylpropoxy]oxane Sodium hydride (60%) (1.72 g, 44.8 mmol) was added to a solution of <strong>[1996-44-7]2,4-difluorobenzenethiol</strong> (CAS no. 1996-44-7) (4.6 mL, 40 mmol) in THF (150 mL) at 0 C., under argon. The mixture was allowed to warm to room temperature and 2-(3-bromopropoxy)oxane (CAS no. 33821-94-2) (7.6 mL, 45 mmol) was added. The reaction was stirred at ambient temperature for 16 hours. The mixture was poured into ice/water (250 mL) and extracted with ethyl acetate (250 mL). The organic extract was washed with brine, dried (MgSO4) and the solvent removed under reduced pressure. The residue was purified by flash chromatography, eluding with 0-10% ethyl acetate in isohexane afford the product (10.8 g, 84%). 1H NMR 6 (400 MHZ, CDCl3): 1.49-1.61 (m, 4H), 1.65-1.73 (m, 1H), 1.75-1.90 (m, 3H), 2.96 (t, 2H), 3.46-3.52 (m, 2H), 3.79-3.87 (m, 2H), 4.55-4.56 (m, 1H), 6.80-6.86 (m, 2H), 7.38-7.44 (m, 1H).

Reference： [1]Patent: US2008/171734,2008,A1 .Location in patent: Page/Page column 43

35
[ 1065586-30-2 ]
[ 1996-44-7 ]
[ 1065584-83-9 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 10℃; for 5h;	EXAMPLE 12 7-(2-(2,4-Difluorophenylthio)ethyl)-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine, Method A To a solution of the title D compound of Example 1, 2-{5-amino-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl}ethyl methanesulfonate (0.06 g, 0.165 mmol) in dry DMF (5 mL), <strong>[1996-44-7]2,4-difluorobenzenethiol</strong> (0.33 mmol) and 0.06 mL of DIEA are added, and the solution is stirred at 10 C. for 5 h. The reaction mixture is cooled to RT, and the solvent is removed under reduced pressure. To the residue, acetonitrile is added and the solution is stirred at 60 C. for 0.5 h. The solution is then cooled to RT, and the resulting solids are collected by filtration to give 7-(2-(2,4-difluorophenylthio)ethyl)-2-(furan-2-yl)-7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine: LC/MS (M+1=412.91). 1H NMR (DMSO-d6, 400 MHz) delta 3.40 (m, 2H), 4.32 (m, 2H), 6.56 (m, 1H), 6.72 (m, 1H), 7.05 (m, 1H), 7.12 (m, 1H), 7.22 (m, 2H), 7.53 (m, 3H), 7.92 (s, 1H). Anal. calculated for (C19H14F2N6OS): C, 55.33; H, 3.42; F, 9 21; N, 20 38; 0, 3.88; S, 7.77. Found C, 55.01; H, 3 75; N, 21.95; S, 6.89.

Reference： [1]Patent: US2008/242672,2008,A1 .Location in patent: Page/Page column 25

36
[ 1057255-99-8 ]
[ 1996-44-7 ]
[ 1057256-16-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 123 - 126

37
[ 696-62-8 ]
[ 1996-44-7 ]
[ 1170116-17-2 ]

Reference： [1]Tetrahedron Letters,2009,vol. 50,p. 3661 - 3664

38
[ 540523-72-6 ]
[ 1996-44-7 ]
[ 1125597-68-3 ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 1156 - 1171

39
[ 864543-61-3 ]
[ 1996-44-7 ]
3-(2-chlorophenyl)-6-(2,4-difluorophenylsulfanyl)-1H-pyrazolo[3,4-d]pyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a 0 C. solution of <strong>[1996-44-7]2,4-difluorothiophenol</strong> (Aldrich) (116 muL, 0.972 mmol) was added potassium tert-butoxide (Aldrich) (1.0M solution in tetrahydrofuran, 988 muL, 0.988 mmol), and the resulting yellow suspension was diluted with 5 mL tetrahydrofuran and stirred for 5 minutes at 0 C. The cooling bath was removed and the suspension was stirred for another 15 minutes at room temperature, and 3-(2-chlorophenyl)-6-methanesulfonyl-1H-pyrazolo[3,4-d]pyrimidine (100 mg, 0.324 mmol) was then added as a powder. The resulting brown suspension was refluxed for 17 hours. The reaction mixture was cooled to ambient temperature and then concentrated. The yellow solid residue was diluted with 20 mL ethyl acetate and 20 mL of saturated aqueous ammonium chloride. The aqueous phase was extracted with ethyl acetate (2*20 mL). The combined organic phases were dried over magnesium sulfate, filtered, and concentrated to give the crude product as a yellow solid. Purification using preparative thin layer chromatography with 20% ethyl acetate in hexanes gave the title compound (64 mg, (M+H)+=375, M.P.=177.6-183.2 C.).

Reference： [1]Patent: US2005/203091,2005,A1 .Location in patent: Page/Page column 41-42

40
[ 930-68-7 ]
[ 1996-44-7 ]
(R)-3-(2,4-difluorophenylthio)cyclohexanone [ No CAS ]
[ 1215843-26-7 ]

Reference： [1]Journal of Organic Chemistry,2010,vol. 75,p. 2089 - 2091

41
dodecylisonitrilegold(I) chloride [ No CAS ]
[ 1996-44-7 ]
[ 1233958-11-6 ]

Reference： [1]Zeitschrift fur Naturforschung, B: Chemical Sciences,2009,vol. 64,p. 1491 - 1499

42
[ 28587-97-5 ]
[ 1996-44-7 ]
[ 1233958-07-0 ]

Reference： [1]Zeitschrift fur Naturforschung, B: Chemical Sciences,2009,vol. 64,p. 1491 - 1499

43
[ 940891-97-4 ]
[ 1996-44-7 ]
1-(2,6-difluorophenyl)-7-[(2,4-difluorophenyl)thio]-2H-quinolizin-2-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 411 - 416

44
[ 1996-44-7 ]
[ 75-03-6 ]
[ 1084334-19-9 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In acetonitrile; at 80℃; for 2h;	Preparation of Intermediate 9 1-(Ethylsulfonyl)-2,4-difluorobenzene To thick-walled, reaction pressure tube was added <strong>[1996-44-7]2,4-difluorobenzenethiol</strong> (1500 mg, 10.26 mmol), iodoethane (1.095 mL, 13.34 mmol), acetonitrile (20 mL), and triethylamine (1.860 mL, 13.34 mmol). The vessel was capped and heated at 80 C. for 2 hours. After cooling to room temperature, the reaction mixture was concentrated in vacuo. Methylene chloride was added and the mixture was washed with water three times. The organic layer was concentrated to provide crude 4-(ethylthio)-1,3-difluorobenzene which was used without further purification. To this material (1700 mg, 9.76 mmol) in acetic acid (10 mL) was added hydrogen peroxide (30% in H2O, 4.7 mL, 48.8 mmol). The mixture was refluxed for 2 hours. After cooling to room temperature, the reaction mixture was added to methylene chloride and washed with water three times. The organic layer was dried with sodium sulfate, filtered, and concentrated. The resulting residue was purified by flash chromatography (silica gel, 0-100% ethyl acetate /hexane) to give 1-(ethylsulfinyl)-2,4-difluorobenzene (1.2 g, 6.31 mmol) as white oil. 1H NMR (CDCl3, 500 MHz) delta 7.69-7.86 (m, 1H), 7.03-7.17 (m, 1H), 6.80-6.94 (m, 1H), 3.05 (dd, J=13.75, 7.15 Hz, 1H), 2.83 (dd, J=13.75, 7.15 Hz, 1H), 1.22 (t, J=7.42 Hz, 3H) ; MS (ESI) 191.1 (M+H). To a solution of 1-(ethylsulfinyl)-2,4-difluorobenzene (1100 mg, 5.78 mmol) in 2-propanol (10 mL) was added water (10 mL) and OXONE (4622 mg, 7.52 mmol). The mixture was stirred at room temperature for 16 hours. The reaction mixture was then filtered and the filtrate was concentrated. The resulting crude material was dissolved in ethyl acetate and was washed with saturated aqueous sodium chloride twice. The organic layer was dried with sodium sulfate, filtered, and concentrated. The residue obtained was then purified by flash chromatography (silica gel, 0-100% ethyl acetate /hexane) to give Intermediate 9 (600 mg, 50% yield) as a white oil. 1H NMR (CDCl3, 500 MHz) delta 7.90-8.02 (1H, m), 6.90-7.12 (2H, m), 3.30 (2H, q, J=7.3 Hz), 1.30 (3H, t, J=7.4 Hz) ; MS (ESI) 207.1 (M+H).

Reference： [1]Patent: US2011/251221,2011,A1 .Location in patent: Page/Page column 16-17

45
[ 1345021-18-2 ]
[ 1996-44-7 ]
[ 1345020-84-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 6316 - 6328

46
[ 1345021-18-2 ]
[ 1996-44-7 ]
C₁₂H₁₀F₂N₂O₄S₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; copper(l) iodide; 2.9-dimethyl-1,10-phenanthroline; In toluene; for 8h;Inert atmosphere; Reflux;	General procedure: Treatment of aryl iodide (1 mmol) with various aryl thiol (1.1 mmol) in the presence of copper iodide (0.1 mmol), neocuproine (0.1 mmol), and potassium phosphate (1.5 mmol) in toluene (10 mL) at reflux under N2 for 8 h resulted in a sticky mixture. The resulting mixture was neutralized by 1 N HCl (1.5 mL) and then evaporated. The residue was extracted with ethyl acetate (15 mL × 3), and the organic layers were concentrated to give 2-aryl- or 2-alkylsulfanylbenzenesulfonamide. From aryl bromide: A mixture of aryl bromide (1 mmol), aryl thiol (1.1 mmol), and K2CO3 (2 mmol) in ethanol (15 mL) was heated to reflux. After 24 h, the resulting mixture was neutralized to pH 7 with saturated NH4Cl and then evaporated. The residue was extracted with ethyl acetate (15 mL × 3), and the organic layers were concentrated to give 2-aryl- or 2-alkylsulfanylbenzenesulfonamide.

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 6316 - 6328

47
[ 1996-44-7 ]
[ 102072-83-3 ]
[ 1355613-36-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 500 - 503

48
[ 1996-44-7 ]
[ 40381-90-6 ]
[ 1392150-43-4 ]

Yield	Reaction Conditions	Operation in experiment
66%		A solution of 362 mg (1.05 eq) of potassium hydroxide in 10 mL of ethanol is added, under nitrogen, to a solution of 698 mu^ (6.16 mmol) of 2,4-difluorobenzenethiol in 30 mL of ethanol. The reaction medium is stirred at room temperature for 15 minutes and then cooled in ice before adding a solution of 1.015 g (0.95 eq) of 2,6- dichloronicotinonitrile in 30 mL of ethanol. The reaction medium is stirred for 2 hours at 0-5C. 63 mL of a 0.1N HCl solution is added to stop the reaction. Water is added and the producted is extracted with ethyl acetate. The organic phase is dried on anhydrous magnesium sulfate, filtered and evaporated. The residue is purified by silica gel chromatography (eluent: cyclohexane/ethyl acetate 94:6) to yield 1.09 g (66%) of 2- chloro-6-(2,4-difluorophenylthio)-nicotinonitrile in the form of a white solid.LCMS (IE, m/z): (M+l) 282,98.1H NMR: deltaEta ppm (400 MHz, DMSO): 8,24 (1H, d, CH), 7,77-7,85 (1H, m, CH), 7,52- 7,63 (1H, m, CH), 7,25-7,35 (2H, m, CH), 2,41 (3H, s, CH3).
66%		2-chloro-6-(2,4-difluorophenylthio)nicotinonitrile A solution of 362 mg (1.05 eq) of potassium hydroxide in 10 mL of ethanol is added, under nitrogen, to a solution of 698 muL (6.16 mmol) of 2,4-difluorobenzenethiol in 30 mL of ethanol. The reaction medium is stirred at room temperature for 15 minutes and then cooled in ice before adding a solution of 1.015 g (0.95 eq) of <strong>[40381-90-6]2,6-dichloronicotinonitrile</strong> in 30 mL of ethanol. The reaction medium is stirred for 2 hours at 0-5 C. 63 mL of a 0.1N HCl solution is added to stop the reaction. Water is added and the producted is extracted with ethyl acetate. The organic phase is dried on anhydrous magnesium sulfate, filtered and evaporated. The residue is purified by silica gel chromatography (eluent: cyclohexane/ethyl acetate 94:6) to yield 1.09 g (66%) of 2-chloro-6-(2,4-difluorophenylthio)-nicotinonitrile in the form of a white solid. LCMS (IE, m/z): (M+1) 282.98. 1H NMR: deltaH ppm (400 MHz, DMSO): 8.24 (1H, d, CH), 7.77-7.85 (1H, m, CH), 7.52-7.63 (1H, m, CH), 7.25-7.35 (2H, m, CH), 2.41 (3H, s, CH3).
66%	With potassium hydroxide; In ethanol; at 0 - 5℃; for 2h;Inert atmosphere;	A solution of 362 mg (1.05 eq) of potassium hydroxide in 10 mL of ethanol is added, under nitrogen, to a solution of 698 muL (6.16 mmol) of 2,4-difluorobenzenethiol in 30 mL of ethanol. The reaction medium is stirred at room temperature for 15 minutes and then cooled in ice before adding a solution of 1.015 g (0.95 eq) of <strong>[40381-90-6]2,6-dichloronicotinonitrile</strong> in 30 mL of ethanol. The reaction medium is stirred for 2 hours at 0-5C. 63 mL of a 0.1N HCl solution is added to stop the reaction. Water is added and the producted is extracted with ethyl acetate. The organic phase is dried on anhydrous magnesium sulfate, filtered and evaporated. The residue is purified by silica gel chromatography (eluent: cyclohexane/ethyl acetate 94:6) to yield 1.09 g (66%) of 2-chloro-6-(2,4-difluorophenylthio)-nicotinonitrile in the form of a white solid. LCMS (IE, m/z): (M+1) 282,98. 1H NMR: deltaH ppm (400 MHz, DMSO): 8,24 (1H, d, CH), 7,77-7,85 (1H, m, CH), 7,52-7,63 (1H, m, CH), 7,25-7,35 (2H, m, CH), 2,41 (3H, s, CH3).

66%		Example 12ter-a: 2-chloro-6-(2,4-difluorophenylthio)nicotinonitrile A solution of 362 mg (1.05 eq) of potassium hydroxide in 10 mL of ethanol is added, under nitrogen, to a solution of 698 (6.16 mmol) of 2,4-difluorobenzenethiol in 30 mL of ethanol. The reaction medium is stirred at room temperature for 15 minutes and then cooled in ice before adding a solution of 1.015 g (0.95 eq) of 2,6- dichloronicotinonitrile in 30 mL of ethanol. The reaction medium is stirred for 2 hours at 0-5C. 63 mL of a 0.1N HCl solution is added to stop the reaction. Water is added and the producted is extracted with ethyl acetate. The organic phase is dried on anhydrous magnesium sulfate, filtered and evaporated. The residue is purified by silica gel chromatography (eluent: cyclohexane/ethyl acetate 94:6) to yield 1.09 g (66%) of 2- chloro-6-(2,4-difluorophenylthio)-nicotinonitrile in the form of a white solid. LCMS (IE, m/z): (M+l) 282.98. 1H NMR: deltaEta ppm (400 MHz, DMSO): 8.24 (1H, d, CH), 7.77-7.85 (1H, m, CH), 7.52- 7.63 (1H, m, CH), 7.25-7.35 (2H, m, CH), 2.41 (3H, s, CH3).
66%		Example 12ter-a: 2-chloro-6-(2,4-difluorophenylthio)nicotinonitrile A solution of 362 mg (1.05 eq) of potassium hydroxide in 10 mL of ethanol is added, under nitrogen, to a solution of 698 (6.16 mmol) of 2,4-difluorobenzenethiol in 30 mL of ethanol. The reaction medium is stirred at room temperature for 15 minutes and then cooled in ice before adding a solution of 1.015 g (0.95 eq) of 2,6- dichloronicotinonitrile in 30 mL of ethanol. The reaction medium is stirred for 2 hours at 0-5C. 63 mL of a 0.1N HCl solution is added to stop the reaction. Water is added and the producted is extracted with ethyl acetate. The organic phase is dried on anhydrous magnesium sulfate, filtered and evaporated. The residue is purified by silica gel chromatography (eluent: cyclohexane/ethyl acetate 94:6) to yield 1.09 g (66%) of 2- chloro-6-(2,4-difluorophenylthio)-nicotinonitrile in the form of a white solid. LCMS (IE, m/z): (M+l) 282,98. 1H NMR: deltaEta ppm (400 MHz, DMSO): 8,24 (1H, d, CH), 7,77-7,85 (1H, m, CH), 7,52- 7,63 (1H, m, CH), 7,25-7,35 (2H, m, CH), 2,41 (3H, s, CH3).
66%	With potassium hydroxide; In ethanol; at 0 - 5℃; for 2h;Inert atmosphere;	A solution of 362 mg (1.05 eq) of potassium hydroxide in 10 mL of ethanol is added, under nitrogen, to a solution of 698 muL (6.16 mmol) of 2,4-difluorobenzenethiol in 30 mL of ethanol. The reaction medium is stirred at room temperature for 15 minutes and then cooled in ice before adding a solution of 1.015 g (0.95 eq) of <strong>[40381-90-6]2,6-dichloronicotinonitrile</strong> in 30 mL of ethanol. The reaction medium is stirred for 2 hours at 0-5C. 63 mL of a 0.1N HCl solution is added to stop the reaction. Water is added and the producted is extracted with ethyl acetate. The organic phase is dried on anhydrous magnesium sulfate, filtered and evaporated. The residue is purified by silica gel chromatography (eluent: cyclohexane/ethyl acetate 94:6) to yield 1.09 g (66%) of 2-chloro-6-(2,4-difluorophenylthio)-nicotinonitrile in the form of a white solid. LCMS (IE, m/z): (M+1) 282,98. 1H NMR: deltaH ppm (400 MHz, DMSO): 8,24 (1H, d, CH), 7,77-7,85 (1H, m, CH), 7,52-7,63 (1H, m, CH), 7,25-7,35 (2H, m, CH), 2,41 (3H, s, CH3).

Reference： [1]Patent: WO2012/101239,2012,A1 .Location in patent: Page/Page column 80
[2]Patent: US2013/85144,2013,A1 .Location in patent: Paragraph 0430; 0431; 0432
[3]Patent: EP2689778,2014,A1 .Location in patent: Paragraph 0256
[4]Patent: WO2014/16433,2014,A1 .Location in patent: Page/Page column 78; 79
[5]Patent: WO2014/16434,2014,A1 .Location in patent: Page/Page column 78-79
[6]Patent: EP2689779,2014,A1 .Location in patent: Paragraph 0332-0334

49
[ 1996-44-7 ]
[ 40381-90-6 ]
[ 1392150-42-3 ]

Reference： [1]Patent: WO2012/101239,2012,A1
[2]Patent: US2013/85144,2013,A1
[3]Patent: EP2689778,2014,A1
[4]Patent: WO2014/16433,2014,A1
[5]Patent: WO2014/16434,2014,A1

50
[ 590-92-1 ]
[ 1996-44-7 ]
[ 926223-52-1 ]

Reference： [1]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 450 - 453

51
[ 1996-44-7 ]
[ 1097779-72-0 ]

Reference： [1]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 450 - 453

52
[ 1996-44-7 ]
[ 1374666-90-6 ]

Reference： [1]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 450 - 453

53
[ 1996-44-7 ]
[ 1097779-74-2 ]

Reference： [1]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 450 - 453

54
[ 1996-44-7 ]
[ 1374667-06-7 ]

Reference： [1]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 450 - 453

55
[ 42456-75-7 ]
[ 1996-44-7 ]
[ 1247819-59-5 ]

Yield	Reaction Conditions	Operation in experiment
39%	With sodium methylate; In methanol;	2-Acetyl-5-chlorothiophene (4.00 g, 24.8 mmol) was added potionwise to fuming nitric acid (24 mL) cooled in an ice-bath. The reaction mixture was then stirred at ambient temperature for 30 minutes and poured into 200 mL ice water. Then solid was precipitated and extracted with ethyl ether. The organic phase was dried, filetered and concentrated in vacuo to get crude product 1-(5-chloro-4-nitrothiophen-2-yl)ethanone (4.50 g) as yellow solid without further purification<strong>[1996-44-7]2,4-difluorobenzenethiol</strong> (4.30 g, 29.4 mmol) was added to a solution of sodium methanol (1.40 g, 26.3 mmol) in methanol (250 mL). The mixture was stirred at ambient temperature for 20 minuters. Then 1-(5-chloro-4-nitrothiophen-2-yl)ethanone (5.50 g, crude product) was added and the mixture was stirred overnight. Water (250 mL) was added and the solid which formed collected by filtration and dried under vacuum at 40oC. The product was recrystallized twice from acetonitrile to give a white solid (3.30 g, 39%). 1H NMR (300 MHz, DMSO) delta 8.50, 8.00, 7.97, 7.95, 7.92, 7.71, 7.70, 7.68, 7.67, 7.65, 7.64, 7.43, 7.40, 7.37, 2.50.

Reference： [1]ACS Medicinal Chemistry Letters,2012,vol. 3,p. 789 - 792,4
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 845 - 849

56
[ 1996-44-7 ]
[ 83909-69-7 ]
[ 1421846-66-3 ]

Reference： [1]ACS Combinatorial Science,2013,vol. 15,p. 130 - 134

57
[ 1373433-13-6 ]
[ 1996-44-7 ]
[ 1373433-06-7 ]

Yield	Reaction Conditions	Operation in experiment
41%	With triethylamine; In N,N-dimethyl-formamide; for 12h;Reflux;	General procedure: To a solution of 2-chloro-6-[3-methoxy-4-[2-(pyrrolidin-1-yl)ethoxy]phenyl]-5H-pyrrolo[3,4-b]pyridin-7(6H)-one (40 mg, 0.10 mmol) in DMF (3 ml) were added thiophenol (0.021 mL, 0.20 mmol) and triethylamine (0.046 mL, 0.30 mmol), then the reaction mixture was refluxed for 12 h. After completion of reaction, the reaction mixture was combined with 20 ml of water ,and extracted with ethyl acetate (20 ml x 2) being washed with water and a sodium bicarbonate. The combined organic layer was dried over anhydrous sodium sulfate, and filtered. The solvent was removed under reduced pressure, and the residue was refined by silica gel column chromatography (10% MeOH/MC) to obtain 27 mg (yield 56%) of the title compound.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 1736 - 1739

58
[ 1996-44-7 ]
C₆H₃F₂S^(1-)*Na⁽¹⁺⁾ [ No CAS ]

Reference： [1]Chemistry - A European Journal,2013,vol. 19,p. 6221 - 6224

59
[ 1996-44-7 ]
C₁₆H₁₁F₂FeNO₄S [ No CAS ]

Reference： [1]Chemistry - A European Journal,2013,vol. 19,p. 6221 - 6224

60
[ 1996-44-7 ]
[ 1452261-76-5 ]

Reference： [1]Synlett,2013,vol. 24,p. 1533 - 1540

61
[ 1996-44-7 ]
(3RS,4SR)-ethyl 4-((E)-2-(2,4-difluorophenylsulfonyl)vinyl)-1-benzylpyrrolidine-3-carboxylate [ No CAS ]

Reference： [1]Synlett,2013,vol. 24,p. 1533 - 1540

62
[ 75-11-6 ]
[ 1996-44-7 ]
[ 1452261-49-2 ]

Reference： [1]Synlett,2013,vol. 24,p. 1533 - 1540

63
[ 74-96-4 ]
[ 1996-44-7 ]
[ 1084334-19-9 ]

Yield	Reaction Conditions	Operation in experiment
67%		Potassium hydroxide (0.42 g, 7.5 mmol) was added to a solution of <strong>[1996-44-7]2,4-difluorothiophenol</strong> (1.0 g, 6.8 mmol) inethanol under inert atmosphere. After stirring for 30 min, ethyl bromide (1.1 g, 10 mmol) was added and the reaction mixture kept at 25 C for 12 h. Aqueous sodium hydroxide (2.0 M, 4.0 mL) was then added, and ethanol was removed under vacuum. The reaction mixture was diluted with water (40 mL), extracted with dichloromethane (3 x 30 mL), and the combined extracts were washed with water (50 mL), brine (50 mL), dried with sodium sulfate and evaporated. The product was purified by chromatography (silica gel; eluent: hexane/chloroform, 9:1) to afford a colourless liquid (0.80 g, 67%). 1H NMR: delta 7.48 (q, J 8.4 Hz, ArZH, 1H), 7.01 (m, ArZH, 2H), 2.93 (q,J 7.4 Hz, SZCH2, 2H), 1.24 (t, J 7.3 Hz, CH2ZCH3)ppm. 13C NMR: 161.7 (dd, J 245.3, 11.3 Hz, ArCF),162.6 (dd, J 244.5, 12.0 Hz, ArCF), 134.7 (dd, J 9.8,3.0 Hz, ArC), 119.7 (dd, J 18.0, 3.8 Hz, ArCS), 112.9(dd, J 21.5, 3.8 Hz, ArC), 105.1 (t, J 26.9 Hz, ArC),28.5 (d, J 2.3 Hz, ArSCH2), 14.8 (ArSCH2CH3) ppm.

Reference： [1]Organic Process Research and Development,2008,vol. 12,p. 1060 - 1077
[2]Supramolecular Chemistry,2014,vol. 26,p. 632 - 641

64
[ 75-61-6 ]
[ 1996-44-7 ]
bromodifluoro(2,4-difluorophenylthio)methane [ No CAS ]

Reference： [1]Organic Letters,2013,vol. 15,p. 5666 - 5669

65
[ 1996-44-7 ]
[ 141599-33-9 ]
[ 1615239-35-4 ]

Yield	Reaction Conditions	Operation in experiment
87%		General procedure: To a solution containing KOH (3.0 eq.) in 1 ml of methanol at room temperature different thiophenols were added (1 eq). After 15 min, 6 (30 mg, 0.083 mmol) was also added. The mixture was allowed to stay to room temperature for 3 h followed by neutralizing with a diluted acetic acid. The mixture was evaporated and the product was purified by flash chromatography.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 81,p. 492 - 498

66
[ 70336-36-6 ]
[ 1996-44-7 ]
C₁₈H₁₄F₂O₂S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 3764 - 3771

67
[ 10419-77-9 ]
[ 1996-44-7 ]
(2,4-difluorophenylsulfanylmethyl)-phosphonic acid diethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%		General procedure: General Procedure H. Preparation of Arylsulfanylmethylphosphonic acid Diethyl Esters(11)Compounds (ha) and (hib) were prepared by the procedure described below and illustrated in Scheme 19. To a room temperature solution of NaH (60% in mineral oil, 1.2 equiv.) in acetonitrileunder an argon atmosphere, arylthiol (9) (1 equiv.) was added dropwise. After 30 mm.,iodomethyldiethylphophonate (10) (1.1 mmol) was added and the mixture was stirred at roomtemperature overnight. After quenching the reaction with water, the mixture was extracted with ethyl acetate. The combined organic layers were dried over Na2SO4 and evaporated to afford the corresponding sulfane (11), which was used directly in the next step. Starting from <strong>[1996-44-7]2,4-difluorobenzenethiol</strong> (9a) and iodomethyldiethylphophonate (10), compound (ha) was obtained in 75 % using the method described in General Procedure H. ?HNMR (300 MHz, CDC13), oe 7.52-7.45 (m, Ar-H, 1H), 6.82-6.75 (m, Ar-H, 2H), 4.06-3.99 (m,-OCH2-, 4H), 3.03 (d, P-CL2-, J= 13.2 Hz, 2H), 0.83-0.76 (m, -CH3, 6H).

Reference： [1]Patent: WO2014/151682,2014,A1 .Location in patent: Page/Page column 89; 90

68
[ 1996-44-7 ]
(2,4-difluorobenzenesulfonylmethyl)phosphonic acid diethyl ester [ No CAS ]

Reference： [1]Patent: WO2014/151682,2014,A1

69
[ 1996-44-7 ]
5-{2-[(2,4-difluorophenyl)sulfonyl]vinyl}-N-methyl-2-(methylsulfanyl)pyrimidin-4-amine [ No CAS ]

Reference： [1]Patent: WO2014/151682,2014,A1

70
[ 1996-44-7 ]
5-{2-[(2,4-difluorophenyl)sulfonyl]vinyl}-N-methyl-2-(methylsulfinyl)pyrimidin-4-amine [ No CAS ]

Reference： [1]Patent: WO2014/151682,2014,A1

71
[ 1996-44-7 ]
5-{2-[2,4-(difluorophenyl)sulfonyl]vinyl}-N²-(1H-indol-5-yl)-N⁴-methylpyrimidine-2,4-diamine [ No CAS ]

Reference： [1]Patent: WO2014/151682,2014,A1

72
[ 1996-44-7 ]
C₂₁H₁₆Cl₃N₃O₂ [ No CAS ]
[ 547756-24-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 273 - 276

73
[ 1996-44-7 ]
C₂₁H₁₅BrCl₃N₃O₂ [ No CAS ]
[ 632628-12-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 273 - 276

74
[ 1996-44-7 ]
C₁₃H₁₀ClN₃OS [ No CAS ]
C₁₉H₁₃F₂N₃OS₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 5473 - 5477

75
[ 1996-44-7 ]
diethyl 2-(bromomethyl)-1-methyl-1H indol 3,5-dicarboxylate [ No CAS ]
diethyl (2-(2,4-difluorophenylthio)methyl)-1-methyl-1H indol 3,5 dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium hydride; In tetrahydrofuran;	General procedure: To a stirred solution of 1.2 equiv of thiophenol and 1.5 equiv of 60% NaH in dry THF (3 mL), 1 equiv of compounds 7 or 8 dissolved in THF (1 mL) were added. The reaction mixture was left overnight, diluted with CH3OH and the solvent removed under reduced pressure. The crude was purified by flash chromatography.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 6014 - 6025

76
[ 1996-44-7 ]
C₁₈H₂₂BrNO₄ [ No CAS ]
C₂₄H₂₅F₂NO₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium hydride; In tetrahydrofuran;	General procedure: To a stirred solution of 1.2 equiv of thiophenol and 1.5 equiv of 60% NaH in dry THF (3 mL), 1 equiv of compounds 7 or 8 dissolved in THF (1 mL) were added. The reaction mixture was left overnight, diluted with CH3OH and the solvent removed under reduced pressure. The crude was purified by flash chromatography.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 6014 - 6025

77
[ 28562-53-0 ]
[ 1996-44-7 ]
4-(2,4-difluoro-phenylsulfanyl)-azetidin-2-one [ No CAS ]