Name: 4052-30-6|4-Methylsulfonylbenzoic acid|97%
Brand: Ambeed
SKU: A107704
Price: 5.0 USD
Availability: InStock
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1
[ 13205-48-6 ]
[ 4052-30-6 ]

Reference： [1]Tetrahedron Letters,1994,vol. 35,p. 3457 - 3460
[2]Catalysis science and technology,2015,vol. 5,p. 320 - 324
[3]Journal and Proceedings - Royal Society of New South Wales,1949,vol. 83,p. 90,93
[4]Journal of the American Chemical Society,1956,vol. 78,p. 3400,3401

2
[ 22821-76-7 ]
[ 4052-30-6 ]

Reference： [1]Journal of the Chemical Society,1945,p. 633,639
[2]Bulletin de la Societe Chimique de France,1946,p. 139,142

3
[ 67-56-1 ]
[ 4052-30-6 ]
[ 22821-70-1 ]

Reference： [1]Journal of the Chemical Society,1948,p. 1506

4
[ 98-10-2 ]
[ 4052-30-6 ]
[ 22821-76-7 ]

Reference： [1]Journal of the Chemical Society,1946,p. 763,766

5
[ 98-10-2 ]
[ 4052-30-6 ]
[ 22821-76-7 ]
[ 17574-50-4 ]

Reference： [1]Journal of the Chemical Society,1946,p. 763,766
[2]Journal of the Chemical Society,1946,p. 763,766

6
[ 98-10-2 ]
[ 4052-30-6 ]
[ 22821-76-7 ]
[ 857488-42-7 ]

Reference： [1]Journal of the Chemical Society,1946,p. 763,766
[2]Journal of the Chemical Society,1946,p. 763,766

7
[ 4052-30-6 ]
[ 40913-92-6 ]

Yield	Reaction Conditions	Operation in experiment
92.6%	With oxalyl dichloride; In dichloromethane; N,N-dimethyl-formamide; at 20℃; for 3h;	P-Methanesulfonylbenzoic acid (10 g, 0.050 mol)Suspended in 50 mL of dry dichloromethane,Oxalyl chloride (15 mL, 0.150 mol) was added and 1 drop of DMF was added dropwise. After stirring for 3 h at room temperature,The reaction was stopped and the reaction mixture was concentrated to dryness under reduced pressure to give 10.1 g of a white solid, yield: 92.6%.
69%	With oxalyl dichloride; In dichloromethane; at 0 - 25℃; for 0.5h;	General procedure: The purchased acids (14.40 mmol) was added into 5 mL DCM andcooled to 0 C. After the oxalyl chloride (1.50 mL, 17.30 mmol) wasadded drop wise, the mixture was removed to room temperature andstirred for 30 min. The solvent was evaporated for use.To a cooled solution of 5 (3.70 g, 17.30 mmol) in 20 mL DCM wasadded Et3N (3.00 mL, 21.60 mmol) then the prepared chloride wasadded drop wise. The mixture was stirred at room temperature for 1 h.The solvent was evaporated under reduced pressure and the residuewas purification by column chromatography with dichloromethane/methanol as eluent on silica gel to give the derivatives7a-7h.
	With thionyl chloride; In 1,2-dichloro-ethane; for 12h;Heating / reflux;	4-methanesulfonylbenzoyl chloride (0.24 g, 1.1 MMOL, prepared from heating 4- METHANESULFONYLBENZOIC acid and thionylchloride in 1, 2-dichloroethane at reflux overnight)

	With oxalyl dichloride; In DMF (N,N-dimethyl-formamide); dichloromethane; at 0 - 20℃; for 3h;	This example illustrates the preparation of 4-hydroxy-3, 5-diisopropylphenyl)- (4- (methylsulfonyl) phenyl) methanone (CY177). To a solution of <strong>[4052-30-6]4-methylsulfonylbenzoic acid</strong> (4.08 g, 24 mmol) and oxalyl chloride (3.9 mL, 44 mmol) in DCM (70 mL) at 0 C was added three drops of DMF. The reaction mixture was stirred at room temperature for 3 hours and concentrated on a rotavapor. The residue was dissolved in 20 mL of DCM and was added into a suspension of 2, 6-diisopropylphenol (2.12 g, 11.9 mmol) and aluminum chloride (1.6 g, 12 mmol in 50 mL of DCM. After being stirred for 14 hour, the reaction mixture was poured into 100 mL of ice-water and extracted with diisopropyl ether (2x 100 mL). The organic layer was washed accordingly with IN HC1, saturated aqueous NaHCO3, and brine, and was dried over anhydrous MgS04. After filtration, the solution was condensed on a rotary evaporator. The crude product was suspended in 100 mL of methanol and 30 mL of water. The resultant suspension was treated with an excess amount of solid NaOH for 16 hour at room temperature and acidified by IN HC1 to pH of 4. The reaction mixture was extracted with ethyl acetate (2x 100 mL). After washing with saturated aqueous NaHCO3 and brine, the organic layer was dried over anhydrous Na2S04 and filtered. The solution was concentrated and the residue was purified by flash silica gel chromatography to afford the desired product as a yellow solid (550 mg, Yield 13%). lH NMR (500 MHz, CDC13) S 1.27 (s, 6H), 1.29 (s, 6H), 3.12 (s, 3H), 3. 18 (hept, J= 6.9 Hz, 2H), 5.40 (br s, 1H), 7. 57 (s, 2H), 7.90 (dd, J= 6.6, 1.7 Hz, 2H), 8. 06 (dd, J = 6. 5,1. 7 Hz, 2H); Anal. Calcd for (Cl9H21FO2 + H) + : 361. Found: 361.
	With thionyl chloride;Heating / reflux;	Example 5 p-Methylsulfonyl-benzoyl Chloride A mixture of 11.2 g (0.056 mol) of p-methylsulfonyl-benzoic acid prepared in Example 4 and 30 ml of thionyl chloride were heated under reflux to give a clear solution. Removal of the excess of thionyl chloride under reduced pressure obtained white solid and without purification put into the next reaction.
	With thionyl chloride; In 1,2-dichloro-ethane;Heating / reflux;	The above N-hydroxyamidine (0.24 g, 1.0 mmol) was dissolved in glacial acetic acid (12 mL) and 4-methanesulfonylbenzoyl chloride (0.24 g, 1.1 mmol, prepared from heating 4-methanesulfonylbenzoic acid and thionylchloride in 1,2-dichloroethane at reflux overnight) was added. The reaction mixture was stirred overnight at ambient temperature and then heated at reflux for 1 h. The mixture was concentrated in vacuo and the residue was dissolved in a mixture of 1 N hydrochloric acid (10 mL) and water (50 mL). The aqueous solution was extracted with diethyl ether (3×15 mL). The organic extracts were discarded and the aqueous phase was made alkaline with 4 N sodium hydroxide and then extracted with ethyl acetate (2×30 mL). The combined organic extracts were evaporated and the residue was dissolved in 1 N hydrochloric acid (10 mL). The mixture was evaporated and re-evaporated twice with acetonitrile to give a solid residue that was crystallised from ethyl acetate. This afforded 0.25 g of the title compound as a solid. 1H NMR (400 MHz, CDCl3) delta 1.5-1.7 (m, 5H), 1.85-2.0 (m, 5H), 2.0-2.25 (m, 5H), 2.52-2.64 (m, 2H), 2.87 (t, 2H), 3.12 (s, 3H), 3.15-3.22 (m, 1H), 3.62-3.70 (m, 2H), 8.12 (d, 2H), 8.33 (d, 2H), 12.15 (brs). HPLC: Rt=8.88 min. reflux
	With thionyl chloride; In dichloromethane; toluene; at 60 - 80℃; for 44h;	To a stirred solution of 4-methylsulphonylbenzoic acid (100 mg, 0.48 mmol) in DCM (2 mL) was added SOCl2 (52 muL, 0.73 mmol) and toluene (2 mL) and the resulting reaction was stirred at 60 0C for 20 hours. A further charge Of SOCl2 (100 muL, 1.45 mmol) was added and the reaction was heated at 80 0C for a further 24 hours. Volatiles were removed at reduced pressure and the crude product used in subsequent steps without further purification.
6.54 g	With thionyl chloride; In tetrahydrofuran;	To a solution of 4-(methylsulfonyl)benzoic acid 1 (6.0 g, 30.0 mmol) in tetrahydrofuran (20 mL) was added 5 ml. of sulfurous dichloride. The reaction was stirred at 60 C until TLC analysis indicated the total consumption of the starting material. The solvent was evaporated to give 6.54 g of 4-(methylsulfonyl)benzoyl chloride 2.
	With oxalyl dichloride; at 0 - 20℃;	General procedure: Acid chloride (20 mol) was prepared from the corresponding carboxylic acid and oxalyl chloride. Acid chloride was added to a solution of 2,3,4,5,6-pentafluoroaniline (22 mmol) in toluene (50 mL). The reaction mixture was stirred for 24 h under reflux. After cooling to room temperature, the precipitate was filtered off, washed with water, and recrystallized from toluene or ethyl acetate/hexane to give the products 1 (the crude mixture was sometimes purified by flash chromatography if necessary).
	With thionyl chloride; In toluene; for 3h;Reflux;	Thionyl chloride (0.356 g; 3 mmol) was added to a mixture of 4-(methylsulfonyl)benzoic acid (0.200 g, 1 mmol) in toluene and themixture was heated at reflux for 3 h. The resultant acid chloride wasdropwised to a mixture of Compound 4 (0.279 g, 1 mmol) and DIPEA(0.258 g, 2 mmol) in dichloromethane (15 ml) at room temperature.The solution was stirred for overnight, then concentrated in vacuo. Theresidue was purified by silica gel column (DCM/MeOH = 20/1) toafford TPB6 (0.409 g, yield: 89%); purity: 97%; mp: 267.6-268.9 C;1H-NMR (d6-DMSO): delta = 10.88 (s, 1H), 8.20 (dd, J = 8.7, 2.1 Hz, 3H),8.17 (dd, J = 6.9, 0.8 Hz, 1H), 8.12 (dd, J = 8.7, 2.7 Hz, 3H), 7.79 (d,J = 8.8 Hz, 1H), 7.71 (dd, J = 7.2, 0.8 Hz, 1H), 7.06 (t, J = 7.1 Hz,1H), 3.31 (s, 3H); 13C-NMR (d6-DMSO): delta = 165.13 (s), 148.00 (s),146.12 (s), 143.92 (s), 139.32 (s), 138.84 (s), 131.03 (s), 129.24 (s),128.03 (s), 127.95 (s), 127.67 (s), 125.72 (s), 124.69 (s), 124.53 (s),124.15 (s), 120.65 (s), 114.90 (s); HR-ESI-MS for C20H15O3N4Cl2S([M + H]+) Calcd: 461.0242; Found: 461.0234.

Reference： [1]Tetrahedron,2016,vol. 72,p. 1787 - 1793
[2]Patent: CN105153055,2017,B .Location in patent: Paragraph 195-0197
[3]Canadian Journal of Chemistry,1984,vol. 62,p. 2330 - 2336
[4]Bioorganic and medicinal chemistry,2020,vol. 28
[5]Bulletin de la Societe Chimique de France,1946,p. 139,142
[6]Journal of medicinal chemistry,1968,vol. 11,p. 1023 - 1028
[7]Chemical and Pharmaceutical Bulletin,1980,vol. 28,p. 2045 - 2051
[8]Journal of Medicinal Chemistry,1988,vol. 31,p. 1762 - 1767
[9]European Journal of Medicinal Chemistry,1997,vol. 32,p. 433 - 443
[10]Pesticide Science,1999,vol. 55,p. 909 - 918
[11]Bioorganic and Medicinal Chemistry,2003,vol. 11,p. 5539 - 5544
[12]Journal of the American Chemical Society,2001,vol. 123,p. 4849 - 4850
[13]Journal of Medicinal Chemistry,2000,vol. 43,p. 859 - 872
[14]Patent: WO2004/54973,2004,A2 .Location in patent: Page 30
[15]Patent: WO2005/63665,2005,A1 .Location in patent: Page/Page column 22-23
[16]Patent: EP1193261,2002,A1 .Location in patent: Page 18
[17]Patent: US2004/58977,2004,A1 .Location in patent: Page/Page column 8; 14
[18]Patent: US2005/107434,2005,A1 .Location in patent: Page/Page column 14
[19]Patent: WO2010/86403,2010,A1 .Location in patent: Page/Page column 106
[20]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 3134 - 3141
[21]Journal of Organic Chemistry,2015,vol. 80,p. 5611 - 5624
[22]European Journal of Organic Chemistry,2017,vol. 2017,p. 2280 - 2289
[23]Advanced Synthesis and Catalysis,2017,vol. 359,p. 2241 - 2246
[24]Journal of Organic Chemistry,2017,vol. 82,p. 8716 - 8724
[25]Patent: WO2019/118528,2019,A1 .Location in patent: Paragraph 0079-0080
[26]Tetrahedron Letters,2020,vol. 61
[27]Bioorganic and Medicinal Chemistry,2020,vol. 28

8
[ 55424-42-5 ]
[ 4052-30-6 ]
[ 36158-01-7 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In N,N-dimethyl-formamide

Reference： [1]Current Patent Assignee: SPARAMEDICA; ROCHE HOLDING AG - DE2135713, 1972, A1 [Chem.Abstr., 1972, vol. 76, # 140794][Chem.Abstr., 1972, vol. 76, # 140794]

9
[ 67198-21-4 ]
[ 4052-30-6 ]
N-((1S,2S)-2-Dimethylamino-cyclohexyl)-4-methanesulfonyl-benzamide [ No CAS ]

Reference： [1]Patent: BE860727,1978,
Patent: DE2749984,1978,
Chem.Abstr.,1978,vol. 89

10
[ 67198-26-9 ]
[ 4052-30-6 ]
N-((1R,2R)-2-Dimethylamino-cyclohexyl)-4-methanesulfonyl-N-methyl-benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	(i) carbonyldiimidazole, THF, (ii) /BRN= 4952712/; Multistep reaction;

Reference： [1]Current Patent Assignee: PFIZER INC - BE860727, 1978, A [Chem.Abstr., 1978, vol. 89, # 146632][Chem.Abstr., 1978, vol. 89, # 146632]

11
[ 186581-53-3 ]
[ 4052-30-6 ]
[ 22821-70-1 ]

Reference： [1]Magnetic Resonance in Chemistry,1989,vol. 27,p. 585 - 591

12
[ 4052-30-6 ]
[ 22821-77-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tetrahydroborate; boron trifluoride diethyl etherate; In tetrahydrofuran; at 0 - 20℃;	4-Methylsulfonylbenzoic acid (12 g, 60.3 mmol, 1 eq) was dissolved in about 100 ml of tetrahydrofuran. The mixture was cooled to 0 C. and then added with sodium borohydride (0.5 to 5 eq). And then the mixture was slowly added with boron trifluoride etherate (0.1 to 6 eq), heated to room temperature, stirred under room temperature over night. TLC showed a new spot with relatively low polarity. The mixture was then slowly poured into cold water and added with ethyl acetate such that the layers were separated. The organic layer was dried by a rotary evaporator to obtain a product. 1H (DMSO, 500 MHz): delta 7.888-7.905 (2H,d), delta 7.543-7.560 (2H,d), delta 4.806 (2H,s), ? 3.035 (3H,s).

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 1757 - 1763
[2]Canadian Journal of Chemistry,1984,vol. 62,p. 2330 - 2336
[3]Patent: US2018/370921,2018,A1 .Location in patent: Paragraph 0130-0133

13
[ 10130-89-9 ]
[ 79-11-8 ]
[ 4052-30-6 ]

Reference： [1]Journal of Organic Chemistry,1991,vol. 56,p. 4974 - 4976

14
[ 3446-89-7 ]
[ 4052-30-6 ]

Reference： [1]Synthetic Communications,1994,vol. 24,p. 2665 - 2673
[2]Archiv der Pharmazie,2017,vol. 350
[3]Tetrahedron,1989,vol. 45,p. 3299 - 3306
[4]Organic Letters,2019,vol. 21,p. 8925 - 8929

15
[ 498-66-8 ]
[ 4052-30-6 ]
exo-bicyclo[2.2.1]heptan-2-yl 4-(methanesulfonyl)benzoate [ No CAS ]

Reference： [1]Chemical Communications,2005,p. 5103 - 5105

16
[ 14062-18-1 ]
[ 4052-30-6 ]
3-(4-methanesulfonylphenyl)-2-(4-methoxyphenyl)-3-oxo-propionic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With sodium hydride; 1,1'-carbonyldiimidazole; In DMF (N,N-dimethyl-formamide); at 20℃; for 12h;	Example 1; [ 3- (4-METHANESULFONYLPHENYL)-2- (4-METHOXYPHENYL)-3-OXO-PROPIONIC] acid ethyl ester. 1g of [4-METHANESULFONY] benzoicacid, 970mg of [4-METHOXYPHENYLACETIC] acid ethyl ester, and 950mg of carbonyldiimidazole were dissoved in [15MUT] of [DIMETHYLFORMAMIDE] and 230mg of sodium hydride were added dropwise to the solution and the mixture was reacted in room temperature for 12 hours. Afterwards, water was added to diute the resultant, followed by extraction with ethyl acetate. The obtained organic layer was dried over anhydrous magnesium sulfate to give 1.5g of the title compound as a light yellow liquid (yield 83%).
83%	With sodium hydride; 1,1'-carbonyldiimidazole; In DMF (N,N-dimethyl-formamide); at 20℃; for 12h;	1 g of 4-methanesulfony benzoicacid, 970 mg of 4-methoxyphenylacetic acid ethyl ester, and 950 mg of carbonyldiimidazole were dissoved in 15 ml of dimethylformamide and 230 mg of sodium hydride were added dropwise to the solution and the mixture was reacted in room temperature for 12 hours. Afterwards, water was added to diute the resultant, followed by extraction with ethyl acetate. The obtained organic layer was dried over anhydrous magnesium sulfate to give 1.5 g of the title compound as a light yellow liquid(yield 83%).

Reference： [1]Patent: WO2004/206,2003,A2 .Location in patent: Page 11
[2]Patent: US2004/2532,2004,A1 .Location in patent: Page 4-5

17
[ 459-03-0 ]
[ 4052-30-6 ]
2-(4-fluorophenyl)-1-(4-methanesulfonylphenyl)-butane-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With sodium hydride; 1,1'-carbonyldiimidazole; In N,N-dimethyl-formamide; for 2h;Heating / reflux;	2 g of 1-(4-fluorophenyl)-propane-2-one, 2.0 g of 4-methanesulfonyl benzoic acid and 1.67 g of carbonyl diimidazole was mixed and dissolved in 10 ml of dimethylformamide. And then, 0.8 g of sodium hydride was slowly added to the solution, and then refluxed for 2 hours. After completing the reaction, 100 ml of water was added thereto, and then extracted with dichloromethane to separate an organic layer. The separated organic layer was dried with anhydrous magnesium sulfate, and a solvent was evaporated under reduced pressure. As a result, 2.46 g of the compound of the formula 21 (yield: 56%) was obtained as a liquid phase.
56%	With sodium hydride; 1,1'-carbonyldiimidazole; In DMF (N,N-dimethyl-formamide); for 2h;Heating / reflux;	2g of [1- (4-FLUOROPHENYL)-PROPANE-2-ONE,] 2. 0g of 4- methanesulfonyl benzoic acid and 1.67g of carbonyl diimidazole was mixed and dissolved in [10ML] of dimethylformamide. And then, 0.8g of sodium hydride was slowly added to the solution, and then refluxed for 2 hours. After completing the reaction, [100ML] of water was added thereto, and then extracted with dichloromethane to separate an organic layer. The separated organic layer was dried with anhydrous magnesium sulfate, and a solvent was evaporated under reduced pressure. As a result, 2.46g of the compound of the formula 21 (yield: [56%)] was obtained as a liquid phase.

Reference： [1]Patent: US2004/72884,2004,A1 .Location in patent: Page/Page column 7
[2]Patent: WO2004/35553,2004,A1 .Location in patent: Page 25-26

18
[ 40784-88-1 ]
[ 4052-30-6 ]
2-(4-ethoxyphenyl)-3-(4-methanesulfonylphenyl)-3-oxo-propionicacid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With sodium hydride; 1,1'-carbonyldiimidazole; In DMF (N,N-dimethyl-formamide); at 20℃; for 12h;	499 mg of 4-ethoxyphenylacetic acid ethyl ester, 480 mg of carbonyldiimidazole, and 0.5 g of 4-methanesulfonyl benzoic acid were dissolved in 10 ml of dimethy formamide, and 119 mg of sodium hydride were slowly addded dropwise to the solution and the mixture was reacted at the room temperature for 12 hours. Afterwards, water was added to diute the resultant, followed by extraction with ethyl acetate. The obtained organic layer was dried over anhydrous magnesium sulfate to give 0.9 g of the titled compound as a light yellow liquid(yield 92%).1H-NMR(400MHz, CDCI3) 6 1H-NMR(400MHz, CDCI3) 6 8.14(d, 2H, J=8.4Hz), 8.04(d, 2H, J=8.4Hz), 6.95(d, 2H, J=8.4Hz), 6.65(d, 2H, J=8.4Hz), 5.56(s, 1H), 4.12(q, 2H, J=6Hz), 3.98(q, 2H, J=6.0Hz), 3.02(s, 3H), 1.33-1.31 (m,6H)

Reference： [1]Patent: WO2005/51941,2005,A1 .Location in patent: Page/Page column 14-15

19
[ 199938-27-7 ]
[ 4052-30-6 ]
[ 199935-82-5 ]

Yield	Reaction Conditions	Operation in experiment
64%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃; for 16h;pH 8.0;	[00395] Compound No. 99 (55 mg, 64%) was prepared by dissolving [4-(3,3-Diphenylpropyl)-1-homopiperazinyl]acetohydrazide (51 mg, 0.139 mmol) in dry CH2Cl2 (2 mL) and adding HOBt (21 mg, 0.155 mmol) and 4-(methylsulfonyl)benzoic acid (29 mg, 0.146 mmol). This mixture was cooled (0 C.) and treatede with EDCI (45 mg, 0.151 mmol) followed by Et3N such that the pH was around 8. After stirring for 16 h at room temperature, the mixture was diluted with CH2Cl2, washed with saturated NaHCO3, brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was applied to silica gel column chromatography (eluent: gradient of 96/4 to 94/6 CH2Cl2/MeOH, v/v) to afford the desired compound, TLC Rf=0.45 (10% CH3OH-CH2Cl2); RPLC tR=6.06 min (>85%), 220 nm (Method B); ESI/MS m/e 549.3 (M++H, C38H36N4O4S).

Reference： [1]Patent: US6686353,2004,B1 .Location in patent: Page/Page column 119

20
[ 4052-30-6 ]
[ 73874-95-0 ]
[ 872037-71-3 ]

Yield	Reaction Conditions	Operation in experiment
90.6%	With benzotriazol-1-ol; dicyclohexyl-carbodiimide; In dichloromethane; at 0 - 22℃; for 23h;	To an ice-cooled slurry of 4-N-Boc-amino-piperidine (400.8 mg, 2.0 mmol), 1-hydroxybenzotriazole (HOBt, 342.3 mg, 2.53 mmol), and p-(methylsulfonyl)-benzoic acid (445.9 mg, 2.23 mmol) in dichloromethane (6 mL) is added 1,3-dicyclohexylcarbodiimide (DCC, 496.7 mg, 2.40 mmol). The reaction mixture is stirred at 22C for 23 hr. The crude product is purified on a silica gel chromatography with ethyl acetate-hexanes to provide a white solid (692.9 mg, 90.6 % yield, ES+(m/z) 383.1 [M+H]).

Reference： [1]Patent: EP1609789,2005,A1 .Location in patent: Page/Page column 16

21
[ 341996-26-7 ]
[ 4052-30-6 ]
1-(7-(4-methanesulfonyloxyphenyl)-carbonyloxyheptyl)-cyclopropene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; toluene-4-sulfonic acid; dicyclohexyl-carbodiimide; In dichloromethane; at 15 - 20℃; for 1.5h;	To a 15 C. solution of 1-(7-hydroxyheptyl)-cyclopropene (537 mg, 3.47 mmol) and 4-methylsulfonyl benzoic acid (764 mg, 3.82 mmol) and N,N-dimethylaminopyridine (42.1 mg, 0.347 mmol) and p-toluenesulfonic acid monohydrate (33.0 mg, 0.173 mmol) in about 30 ml methylene chloride is added a solution of N,N'-dicyclohexylcarbodiimide (85.8 mg, 4.16 mmol) in about 10 ml of methylene chloride. After stirring at room temperature about 90 minutes, the reaction mixture was vacuum filtered through extremely retentive filter paper. Water was added to this filtrate and the mixture stirred about 30 minutes. After the phases were separated, the organic layer was dried over magnesium sulfate and dried in vacuo to give 1.5 g of 70% pure 1-(7-(4-methanesulfonyloxyphenyl)-carbonyloxyheptyl)-cyclopropene.

Reference： [1]Patent: US2005/65033,2005,A1 .Location in patent: Page/Page column 17

22
[ 776328-48-4 ]
[ 4052-30-6 ]
[ 874900-25-1 ]

Yield	Reaction Conditions	Operation in experiment
93.2%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 3h;	Step 2; To a solution of N-{5-[(methylamino)methyl]-4-[(Z)-2-(4-nitrophenyl)vinyl]-1,3-thiazol-2-yl}acetamide (100 mg) in 1 ml of dichloromethane were added 4-(methylsulfonyl)benzoic acid(60.2 mg) , HOBt (61 mg) and EDCI HC1 (86.5 mg), and then themixture was stirred for 3 hr at 20 C. The reaction mixturewas diluted with 4 ml of dichloromethane and washed withwater. The organic layer was dried over diatomaceous earth andevaporated under vaccum to give crude pale yellow oil (144.3mg, 93.2 %) . The crude oil was purified by preparative silicagel thin-layer chromatography with chloroform / methanol(15:1) as an eluent to give N-({2-(acetylamino)-4-[(Z)-2-(4-nitrophenyl)vinyl]-1,3-thiazol-5-yl}methyl)-N-methyl-4-(methylsulfonyl)benzamide (144.3 mg)

Reference： [1]Patent: WO2006/11631,2006,A2 .Location in patent: Page/Page column 94

23
[ 56602-33-6 ]
[ 4052-30-6 ]
2-((Propyl)amino)-N-[2-[[(cis)-2-[[4-(methylsulfonyl)benzoyl]amino]cyclohexyl]amino]-2-oxoethyl]-5-trifluoromethyl benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 4-methyl-morpholine;palladium-carbon; In 1,4-dioxane; hydrogenchloride; methanol; ethyl acetate; N,N-dimethyl-formamide;	(108a) For this preparation, Example 104, step 104c, was altered as follows. [(Cis)-2-[[[[(2-(allylamino)-5-trifluoromethyl)benzoyl]amino]acetyl]amino]cyclohexyl]carbamic acid tert-butyl ester from 104(b) (360 mg) was dissloved in 4M HCl/dioxane(10 mL). After stirring for 2 h, the solution was concentrated. A portion (300 mg) of the resulting residue was dissolved in MeOH (5 mL) and 10% Pd/C was added. A hydrogen balloon was added and the solution was stirred for 2 h. The palladium was filtered and the solution was concentrated. A portion (50 mg) of the resulting residue was dissolved in DMF (2.5 mL). After cooling to 0 C., 4-methylmorpholine (63 mg) and <strong>[4052-30-6]4-methylsulfonylbenzoic acid</strong> (30 mg) were added. BOP Reagent (83 mg) was added, and the mixture was stirred at rt for 18 h. EtOAc was added along with 1 N HCl solution. The EtOAc layer was washed with 1 N HCl, NaHCO3 solution, and brine. The EtOAc was dried (MgSO4), filtered, and concentrated. Reverse phase HPLC purification (gradient elution, water/acetonitrile/TFA) provided the title benzamide (15 mg). MS found: (M+H)+=583.3.

Reference： [1]Patent: US2003/4151,2003,A1

24
[ 6938-68-7 ]
[ 4052-30-6 ]
cyclohexyl-[5-(4-methanesulfonyl-phenyl)-3-methyl-3H-[1,3,4]thiadiazol-2-ylidene]-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26%	With sodium hydrogencarbonate; sodium chloride; trichlorophosphate; In 1,4-dioxane;	Cyclohexyl-[5-(4-methanesulfonyl-phenyl)-3-methyl-3H-[1,3,4]thiadiazol-2-ylidene]-amine To a mixture of 4-methylsulfonyl-benzoic acid (2.5 mmol, 500 mg), <strong>[6938-68-7]2-methylthiosemicarbazide</strong> (5a) (2.5 mmol, 468 mg) in anhydrous dioxane (5 mL) at 65 C., POCl3 (3 mmol, 280 muL) was added, and the mixture was warmed at 95 C. for 5 hours. The solvent was removed by distillation under reduced pressure to give a crude material which was basified at pH 8-7 with a saturated solution of NaHCO3. The aqueous phase was extracted with dichloromethane. The organic layer was washed with saturated solution of NaCl, dried over magnesium sulfate, filtered, and distilled to give a residue which was purified by silica gel chromatography (eluted with a gradient of cyclohexane/ethyl acetate finishing with the ratio 80:20) to afford 230 mg of the title compound. Yield: 26%. 1H-NMR (400 MHz, DMSO) delta ppm: 1.25-1.45 (m, 5H), 1.65-1.75 (m, 1H), 1.75-1.95 (m, 4H), 1.70-1.80 (m, 1H), 3.35 (s, 3H), 3.65 (s, 3H), 8.05 (dd, 4H). MS (m/z)/M+1=352.5.

Reference： [1]Patent: US2003/45557,2003,A1

25
[ 79-37-8 ]
[ 4052-30-6 ]
[ 33513-42-7 ]
[ 40913-92-6 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane	168.1 Step 1. Step 1. 4-Methylsulphonylbenzoyl chloride To a stirred solution of 4-methylsulphonyl benzoic acid (1 g, 4.99 mmol) in dry dichloromethane (10 ml) was added oxalyl chloride (0.88 ml, 9.87 mmol) followed by N,N-dimethyl formamide (2 drops). The reaction was stirred at room temperature under argon for 5 hours. The solvent was evaporated in vacuo. The product was used immediately in the next reaction; νmax (CH2 Cl2) 1784 cm-1.

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - US6020368, 2000, A

26
[ 4052-30-6 ]
[ 4205-90-7 ]
[ 87235-71-0 ]

Yield	Reaction Conditions	Operation in experiment
	With 1,1'-carbonyldiimidazole In tetrahydrofuran	2 EXAMPLE 2 EXAMPLE 2 4.40 g (22 mmoles) of p-methylsulfonylbenzoic acid are dissolved in 70 ml of anhydrous tetrahydrofuran, 3.56 g (22 mmoles) of N,N'-carbonyldiimidazole are added and stirred at room temperature for one hour. A solution of 4.60 g (20 mmoles) of 2-(2,6-dichlorophenylimino)-imidazolidine in 50 ml of anhydrous tetrahydrofuran is added dropwise while stirring further and the mixture is allowed to stand at room temperature for 20 hours. The residue from evaporation is triturated with water, separated off, washed with water, dried and recrystallized from dimethylformamide/water (1:1). 5.15 g (62.5% of theory) of 1-(p-methylsulfonylbenzoyl)-2-(2,6-dichlorophenylimino)-imidazolidine of melting point 240°-244° C. are obtained.

Reference： [1]Current Patent Assignee: JLL PARTNERS INC - US4581460, 1986, A

27
[ 4052-30-6 ]
trans-N-[2-(dimethylamino)cyclohexyl]-p-(methanesulfonyl)-benzamide 2-naphthalene sulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	In chloroform-d1;	EXAMPLE 7 trans-N-[2-(dimethylamino)cyclohexyl]-p-(methanesulfonyl)-benzamide 2-naphthalene sulfonate This titled amide was prepared by general procedure A, as in Example 6, using <strong>[4052-30-6]4-methylsulfonylbenzoic acid</strong> in place of the 4-acetylbenzoic acid. The crude product was crystallized from ethylacetate, m.p. 185-186.5, 77% yield. The analytical sample melted at 187-188. uv lambdamax 228 nm (epsilon 14,850); sh 263, sh 267, sh 272, sh 276. ir NH 3380, 3360; N-alkyl 2760; C=O 1640; C=C 1600, 1570; amide II 1545; SO2 /CN/other 1325, 1315, 1290, 1165, 1150, 1095, 970; aromatic/other 860, 785, 750. nmr in CDCl3 (100 MHz) was in accord. Mass spectrum M+ 324. Vpc 100% at 8.1 minutes. Anal. Calcd. for C16 H24 N2 O3 S: C, 59.23; H, 7.46; N, 8.64; S, 9.88. Found: C, 59.14; H, 7.38; N, 8.63; S, 9.92.
77%	In chloroform-d1;	Example 7 trans-N-[2-(dimethylamino)cyclohexyl]-p-(methanesulfonyl)-benzamide 2-naphthalene sulfonate This titled amide was prepared by general procedure A, as in Example 6, using <strong>[4052-30-6]4-methylsulfonylbenzoic acid</strong> in place of the 4-aceylbenzoic acid. The crude product was crystallized from ethylacetate, m.p. 185-186.5, 77% yield. The analytical sample melted at 187-188. uv lambdamax 228 nm (68 14,850); sh 263, sh 267, sh 272, sh 276. ir NH 3380, 3360; N-alkyl 2760; C=O 1640; C=C 1600, 1570; amide II 1545; SO2 /CN/other 1325, 1315, 1290, 1165, 1150, 1095, 970; aromatic/other 860, 785, 750. nmr in CDCl3 (100 MHz) was in accord. Mass spectrum M+ 324. Vpc 100% at 8.1 minutes. Anal. Calcd. for C16 H24 N2 O3 S: C, 59.23; H, 7.46; N, 8.64; S, 9.88. Found: C, 59.14; H, 7.38; N, 8.63; S, 9.92.
77%	In chloroform-d1;	EXAMPLE 7 trans-N-[2-(dimethylamino)cyclohexyl]-p-(methanesulfonyl)-benzamide-2-naphthalene sulfonate This titled amide was prepared by general procedure A, as in Example 6, using <strong>[4052-30-6]4-methylsulfonylbenzoic acid</strong> in place of the 4-acetylbenzoic acid. The crude product was crystallized from ethylacetate, m.p. 185-186.5, 77% yield. The analytical sample melted at 187-188. uv lambdamax 228 nm (epsilon 14,850); sh 263, sh 267, sh 272, sh 276. ir NH 3380, 3360; N-alkyl 2760; C=O 1640; C=C 1600, 1570; amide II 1545; SO2 /CN/other 1325, 1315, 1290, 1165, 1150, 1095, 970; aromatic/other 860, 785, 750. nmr in CDCl3 (100 MHz) was in accord. Mass spectrum M+ 324. Vpc 100% at 8.1 minutes. Anal. Calcd. for C16 H24 N2 O3 S: C, 59.23; H, 7.46; N, 8.64; S, 9.88. Found: C, 59.14; H, 7.38; N, 8.63; S, 9.92.

Reference： [1]Patent: US4098904,1978,A
[2]Patent: US4192885,1980,A
[3]Patent: US4215114,1980,A

28
N-(4-bromo-phenyl)-trifluoroacetamidrazone [ No CAS ]
[ 40913-92-6 ]
[ 4052-30-6 ]
1-(4-bromo-phenyl)-5-(4-methylsulfonyl-phenyl)-3-trifluoromethyl-1H-1,2,4-triazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26%	With pyridine In 1,4-dioxane; dichloromethane	18.b EXAMPLE 18 b) 1-(4-bromo-phenyl)-5-(4-methylsulfonyl-phenyl)-3-trifluoromethyl-1H-1,2,4-triazole To a solution of N-(4-bromo-phenyl)-trifluoroacetamidrazone (6.7 g, 23.7 mmol) and pyridine (2.1 ml, 26.1mmol) in dioxane (40 ml) was added a solution of 4-methylsulfonyl-benzoyl chloride (5.96 g, 27.3 mmol) (prepared in situ from 4-methylsulfonyl-benzoic acid) in dioxane (40 ml). Then the reaction mixture was heated to reflux for 5 hours. After evaporation of dioxane the residue was taken up in dichloromethane, the organic layer was washed with water, 0.1 N HCI, saturated brine, dried over sodium sulfate and evaporated under vacuum. The resulting residue was chromatographed on silica gel using a 95/5 mixture of toluene/dioxane as the eluent, then recrystallized from ethanol to give a white solid (2.8 g, 26 %). m.p. 198°C 1H-NMR (DMSO d6): 3.29 (s, 3H), 7.55 (d, 2H), 7.76 (d, 2H), 7.8 (dd, 2H), 8.02 (dd, 2H) MH+ = 446.

Reference： [1]Current Patent Assignee: THERAMEX SA - EP1099695, 2001, A1

29
N-(2-pyridinyl)-trifluoroacetamidrazone [ No CAS ]
[ 40913-92-6 ]
[ 4052-30-6 ]
1-(2-pyridinyl)-5-(4-methylsulfonyl-phenyl)-3-trifluoromethyl-1H-1,2,4-triazole hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15%	In 1,4-dioxane; toluene	31.b EXAMPLE 31 b) 1-(2-pyridinyl)-5-(4-methylsulfonyl-phenyl)-3-trifluoromethyl-1H-1,2,4-triazole hydrochloride To a solution of N-(2-pyridinyl)-trifluoroacetamidrazone (3.1 g, 15.1 mmol) in dioxane (15 ml) was added a solution of 4-methylsulfonyl-benzoyl chloride (3.6 g, 16.7 mmol) (prepared in situ from 4-methylsulfonyl-benzoic acid) in dioxane (15 ml). Then the reaction mixture was refluxed for 2 hours. After cooling the reaction mixture was filtered and concentrated to dryness. The residue was chromatographed on silica gel using an 85/15 mixture of toluene/dioxane as the eluent, then recrystallized from ethanol to give a white solid (0.94 g, 15 %). m.p. 144 °C 1H-NMR (DMSO d6): 3.27 (s, 3H), 7.6 (t, 1H), 7.8 and 8 (AB, 4H), 7.9 (d, 1H), 8.16 (t, 1H), 8.46 (d, 1H).

Reference： [1]Current Patent Assignee: THERAMEX SA - EP1099695, 2001, A1

30
[ 1071927-10-0 ]
[ 4052-30-6 ]
[ 1071927-25-7 ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 2h;	Production Example 25In 1 ml of N,N-dimethylformamide were dissolved 195 mg of 5- (5- (3, 5-dichlorophenyl) -4, 5- dihydro-5-trifluoromethyl-3-isoxazolyl) -2-methylaniline obtained according to Reference Production Example 5 and 400 mg of <strong>[4052-30-6]4-methylsulfonylbenzoic acid</strong>, and 125 mg of 1- [3- (diethylamino)propyl] -3-ethylcarbodiimide hydrochloride was added thereto at room temperature and stirred for 2 hours. A saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The resultant residue was subjected to silica gel column chromatography to obtain 247 mg of N- (5- (5- (3, 5- dichlorophenyl) -4, 5-dihydro-5-trifluoromethyl-3- isoxazolyl) -2-methylphenyl) -4-methylsulfonylbenzamide <n="128"/>(hereinafter referred to as the present compound (25) ) . The present compound (25) :1H-NMR (CDCl3) delta : 8.17 (IH, d, J = 1.5 Hz), 8.08-8.03 (4H, m) , 7.94 (IH, br s) , 7.55 (IH, dd, J = 7.8, 1.8 Hz), 7.51-7.51 (2H, m) , 7.42 (IH, t, J = 1.9 Hz), 7.32 (IH, d, J = 8.1 Hz), 4.12 (IH, d, J = 17.4 Hz), 3.73 (IH, d, J = 17.4 Hz), 3.10 (3H, s) , 2.39 (3H, s) .

Reference： [1]Patent: WO2008/126665,2008,A2 .Location in patent: Page/Page column 126-127

31
[ 536-90-3 ]
[ 4052-30-6 ]
[ 878598-69-7 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 143.8 mg (0.75 mmol) N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC.HCl) and 91.6 mg (0.75 mmol) 4-dimethylaminopyridine (DMAP) in 2 ml dichloromethane were added 92.3 mg (83.9 muL, 0.75 mmol) 3-methoxy-aniline and the solution stirred at ambient temperature for 5 min. Then this solution was added to 100 mg (0.5 mmol) 4-methanesulfonyl-benzoic acid and the solution stirred at ambient temperature for 18 hours. The reaction mixture was filtered through a cartridge filled with 5 g SCX/silica gel 2:3, pre-washed with 10 ml methanol and 20 ml dichloromethane, and the reaction product eluted with 50 ml dichloromethane. 4-methanesulfonyl-N-(3-methoxy-phenyl)-benzamide was obtained as colourless solid: MS (ISN): 304.4 ((M-H)-.).

Reference： [1]Patent: US2009/36420,2009,A1 .Location in patent: Page/Page column 10

32
[ 1204331-29-2 ]
[ 4052-30-6 ]
[ 1204331-31-6 ]

Yield	Reaction Conditions	Operation in experiment
69%		To a solution of 4-methanesulfonyl-benzoic acid (46 mg, 0.23 mmol) in NN- dimethylformamide (3.0 mL) is added di-imidazol-1-yl-methanone (37 mg, 0.23 mmol) and the reaction is stirred for 45 minutes. The product of Example 47 Step E (100 mg, 0.21 mmol) is added followed by NN-diisopropylethylamine (0.13 mL, 0.73 mmol) and the reaction is stirred overnight. The mixture is diluted with ethyl acetate and washed twice with water, once with brine, dried over Nua2SO4, filtered, and the solvent is removed in vacuo. The crude material is purified via silica gel chromatography using a gradient elution of 0-70% ethyl acetate/hexane to afford the desired product (90 mg, 69%). LCMS: 495.71 (M+H+).

Reference： [1]Patent: WO2010/5783,2010,A1 .Location in patent: Page/Page column 112-113

33
[ 1204331-51-0 ]
[ 4052-30-6 ]
[ 1204331-55-4 ]

Yield	Reaction Conditions	Operation in experiment
82%		To a solution of 4-methanesulfonylbenzoic acid (136 mg, 0.681 mmol) in NN- dimethylformamide (8.0 mL) is added di-imidazol-1-yl-methanone (110 mg, 0.681 mmol) and the mixture is stirred for 90 minutes. The product of Example 68 Step D (300 mg, 0.619 mmol) is then added followed by NN-diisopropylethylamine (0.33 mL, 1.87 mmol) and the reaction is stirred overnight at room temperature. The mixture is diluted with ethyl acetate, washed twice with water, once with brine, dried over Na2SO4, filtered, and the solvent is removed in vacuo to afford the desired product (376 mg, 82%). LCMS: 631.34 (M+H+).

Reference： [1]Patent: WO2010/5783,2010,A1 .Location in patent: Page/Page column 133-134

34
[ 857653-98-6 ]
[ 4052-30-6 ]
4-(5-(4-methanesulfonylphenyl)-[1,2,4]oxadiazol-3-ylmethoxy)piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		4-[5-(4-Methanesulfonylphenyl)-[l,2,4]oxadizol-3-ylmethoxy]piperidine-l-carboxylic acid tert- butyl ester (Example 2): A solution of 4-methanesulfonylbenzoic acid (88 mg, 0.44 mmol) and HOBt (60 mg, 0.44 mmol) in THF (0.8 mL) was treated with EDC (76 mg, 0.44 mmol) and subsequently a suspension of 4-(N-hydroxycarbamimidoylmethoxy)piperidine-l-carboxylic acid tert-butyl ester (Preparation 11, 109 mg, 0.4 mmol) in THF (0.4 mL). The mixture was stirred at rt overnight. A solution OfKO1Bu (205 mg, 1.83 mmol) in THF (0.6 mL) was added, causing formation of a thick, solid precipitate. Sufficient THF (0.3 mL) was added to give a fluid mixture, which was stirred for a further 2 h. The solvent was evaporated, the residue dissolved in a mixture of DMSO (0.3 mL), MeOH (0.4 mL) and DCM (0.4 mL) and purified by RP-HPLC to afford the title compound: deltaH (CDCl3) 1.49 (9H, s), 1.68 (2H, m), 1.95 (2H, m), 3.15 (3H, s), 3.16 (2H, m), 3.75 (IH, m), 3.84 (2H, m), 4.80 (2H, s), 8.17 (2H, d), 8.41 (2H, d).

Reference： [1]Patent: WO2007/3960,2007,A1 .Location in patent: Page/Page column 35

35
[ 1253383-66-2 ]
[ 4052-30-6 ]
[ 1253383-72-0 ]

Yield	Reaction Conditions	Operation in experiment
36%		Example 8: Synthesis of N-(5-Chloro-2-{4-[2-(3,5-dimethyl-pyrazol-l-yl)-acetyl]- piperazin-l-yl}-pyridin-3-yl)-4-methanesulfonyl-benzamide To a solution of 4-methanesulfonyl-benzoic acid (0.030 g, (0.150 mmol) in methylene chloride (2 niL) is added oxalyl chloride (0.017 niL, 0.200 mmol) followed by 1 drop of iV,./V-dimethylformamide. Vigourous bubbling is observed and the reaction mixture is stirred at room temperature for 2h. The mixture is concentrated under a stream of nitrogen. The residue is dissolved in methylene chloride (2 mL) and l-[4-(3-amino-5- chloro-pyridin-2-yl)-piperazin-l-yl]-2-(3,5-dimethyl-pyrazol-l-yl)-ethanone (0.040 g, 0.110 mmol) is added followed by (0.040 mL, 0.220 mmol) Lambdaf,iV-diisopropylethylamine (0.040 mL, 0.220 mmol). The mixture is stirred at room temperature for 3 days then concentrated under a stream of nitrogen. The residue is dissolved in dimethylsulfoxide and purified by reverse phase preparative HPLC to provide, after removal of the eluent, 0.022 g of N-(5-Chloro-2-{4-[2-(3,5-dimethyl-pyrazol-l-yl)-acetyl]-piperazin-l-yl}- pyridin-3-yl)-4-methanesulfonyl-benzamide as a white solid in 36% yield. MS; MH+=531.8

Reference： [1]Patent: WO2010/126851,2010,A1 .Location in patent: Page/Page column 102

36
[ 1220883-81-7 ]
[ 4052-30-6 ]
[ 1220883-84-0 ]

Yield	Reaction Conditions	Operation in experiment
78%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride;dmap; In dichloromethane; at 20℃;	A 10-mL round-bottomed flask was charged with dimer alcohol 11 (20.0 mg, 0.031 mmol), 4-(methylsulfonyl) benzoic acid (12.4 mg, 2 eq), EDC (12 mg, 2 eq) and a catalytic amount of 4-dimethylamino pyridine (DMAP) in 1 mL Of CH2Cl2 at room temperature. The reaction mixture was stirred for 2 h and then quenched with H2O, extracted with EtOAc, dried over MgSO4, and concentrated. The crude product was purified by column chromatography (ethyl acetate/hexane 1/2) to give 19.7 mg (78% yield) of sulfonylbenzoate 12c as an amorphous solid. 1H NMR: (400 MHz, CDCl3): 8.26 (d, J58 Hz, 2H), 8.02 (d, J58 Hz, 2H), 6.02 (s, IH), 5.38 (s, 2H), 5.35 (d, J54 Hz, 2H), 5.31 (d, J54 Hz, 2H), 4.62-4.60 (m, IH), 4.58-4.56 (m, IH), 3.07 (s, 3H), 2.68-2.58 (m, 2H), 2.37-2.26 (m, 4H), 2.19-2.15 (m, 2H), 2.02-1.98 (m, 2H), 1.93-1.88 (m, 2H), 1.79-1.75 (m, 2H), 1.66-1.62 (m, 4H), 1.39-1.37 (m, 2H), 1.39 (s, 3H), 1.36 (s, 3H), 1.30-1.22 (m, 6H), 0.96-0.90 (m, 2H), 0.95 (d, J54 Hz, 6H), 0.87 (d, J58 Hz, 3H), 0.86 (d, J54 Hz, 3H); 13C NMR: (100 MHz: CDCl3) 163.42, 144.10, 142.52, 142.32, 135.37, 130.62, 127.48, 115.56, 114.42, 102.91, 102.86, 89.58, 89.39, 81.07, 80.83, 72.60, 71.65, 52.12, 52.05, 44.35, 44.02, 37.49 37.47, 36.68, 36.63, 34.39, 32.37, 31.08, 30.47, 25.92, 25.89, 24.85, 24.77, 20.12, 20.09, 12.77, 12.65; [alpha]D24 5 +45.01 (c=0.95, CHCl3); IR (thin film) 2939, 2875, 1728, 1646, 1455, 1321, 1269, 1176, 1155, 753; HRMS(ESI) m/z calcd for C45H62Oi2S Na(M+Na)+849.3854; found 849.3831.

Reference： [1]Patent: WO2010/135427,2010,A2 .Location in patent: Page/Page column 62-63

37
[ 851471-38-0 ]
[ 4052-30-6 ]
[ 1190098-45-3 ]

Yield	Reaction Conditions	Operation in experiment
10%	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 16h;	N-(benzo[d][1,3]dioxol-5-yl)-1H-indazole-3-carboxamide (300 mg, 1.1 mmol) was dissolved in DMF (5 mL), 4-(methylsulfonyl)benzoic acid (260 mg, 1.2 mmol), (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (690 mg, 1.2 mmol) and diisopropylethylamine (0.57 mL, 3.3 mmol) were added and the resulting mixture was stirred at room temperature for 16 h. The reaction mixture was partitioned between ethyl acetate and water, the organic phase washed with water (2×), the aqueous phase extracted with ethyl acetate (1×) and the combined organic phases washed with brine, dried over magnesium sulfate and concentrated. The residue was purified by column chromatography eluting using a gradient (petroleum ether 40/60/ethyl acetate 1:0 v/v 9:1) to afford 51 mg (10%) of the title compound.N-(Benzo[d][1,3]dioxol-5-yl)-1-(4-(methylsulfonyl)benzoyl)-1H-indazole-3-carboxamide(LCMS RT=2.49 min, MH+=463.8, 927.3), 1H NMR (DMSO): 10.92 (1H, s), 8.52 (1H, d, J 9.8), 8.38 (2H, d, J 9.8), 8.29 (1H, d, J 9.3), 8.14 (2H, d, J 9.8), 7.81 (1H, t, J 8.6), 7.62 (1H, t, J 8.6), 7.44 (1H, d, J 2.3), 7.21 (1H, dd, J 2.4, 7.8), 6.93 (1H, d, J 9.8), 6.03 (2H, s).

Reference： [1]Patent: US2010/305120,2010,A1 .Location in patent: Page/Page column 46-47

38
[ 123-91-1 ]
[ 4052-30-6 ]
[ 1284251-57-5 ]

Reference： [1]Chemistry - A European Journal,2011,vol. 17,p. 4085 - 4089
[2]Organic Letters,2019,vol. 21,p. 8925 - 8929

39
[ 1072-97-5 ]
[ 4052-30-6 ]
[ 1206968-60-6 ]

Yield	Reaction Conditions	Operation in experiment
32%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;Inert atmosphere;	[Example 3]tert-Butyl 4-[2-(4-methanesulfonylbenzylamino)pyridin-5-yl]piperidine-1-carboxylate (1) N-(5-Bromopyridin-2-yl)-4-methanesulfonylbenzamide To a solution of 4-methanesulfonylbenzoic acid (100 mg, 0.50 mmol) and 2-amino-5-bromopyridine (104 mg, 0.60 mmol) in dry dichloromethane (10 mL) was added 4-(dimethylamino)pyridine (67 mg, 0.55 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (105 mg, 0.55 mmol). The mixture was stirred at room temperature overnight under N2, diluted with water (10 mL) and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/ ethyl acetate=3/1) to give the title compound as a white crystal (56 mg, yield 32%).1H NMR(CDCl3,400 MHz): delta= 3.10(3H, s), 7.90(1H, dd, J=2 Hz, 9 Hz), 8.10(4H, s), 8.32(1H, d, J=9 Hz), 8.39(1H, d, J=2 Hz), 8.55(1H, brs).

Reference： [1]Patent: EP2311822,2011,A1 .Location in patent: Page/Page column 33

40
[ 25888-99-7 ]
[ 10297-73-1 ]
[ 4052-30-6 ]

Yield	Reaction Conditions	Operation in experiment
30%; 68%		General procedure: A round-bottom flask that was flame-dried and cooled under dry air or oxygen atmosphere was charged with alcohol 6 or 33 (0.5 mmol) and THF (2.5 mL). After stirring at 0 C for 5 min, NaH powder (1 mmol, 2 equiv) was added in one portion, and the mixture was allowed to warm to room temperature. The reaction was quenched by addition of saturated NH4Cl (2 mL) after the indicated time, extracted with EtOAc (10 mL×2), and washed by brine (15 mL). The combined organic phase was dried over MgSO4, the solvent was removed under vacuum, and the residue was purified by flash chromatography on silica gel to give the desired ketone product 7 and 34. For isolations of acids 8 and 35/36: the combined aqueous phase was acidified with 2 M HCl, and then extracted with EtOAc (10 mL×2) and washed by brine (15 mL). The combined organic phase was dried over Na2SO4, the solvent was removed under vacuum to give acid product that can be further purified by flash chromatography on silica gel.

Reference： [1]Tetrahedron,2011,vol. 67,p. 3406 - 3411

41
[ 4052-30-6 ]
[ 95-51-2 ]
[ 883049-77-2 ]

Yield	Reaction Conditions	Operation in experiment
76%		(2) (a) Preparation of N-(2-chlorophenyl)-4-(methylsulfonyl)benzamide 3 :To a solution of 4-(methylsulfonyl)benzoic acid 1 (1.0 g, 5 mmol) in 50 mL of dichloromethane was added thionyl chloride (5 mL). The mixture was stirred at ambient temperature for 18 hours. After removal of all solvent, the residue was dissolved in 50 mL of dichloromethane. To the solution was added o-chloroaniline (0.766 g, 6 mmol) followed by 1.4 mL of Et3N. The mixture was stirred at ambient temperature for 2 hours. After washing with IN HC1 and water, the organic layer was concentrated to give N-(2-chlorophenyl)-4-(methylsulfonyl)benzamide 3 as a solid. Yield: 1.18 g, 76%.1HNMR (CDC13) delta (ppm): 8.54 (d, 1H); 8.43 (bs, 1H); 8.12(m, 4H); 7.46 (d, 1H); 7.38 (dd, 1H); 7.15 (dd, lH); 3.10 (s, 3H).

Reference： [1]Patent: WO2012/76898,2012,A1 .Location in patent: Page/Page column 45

42
[ 4052-30-6 ]
[ 110-83-8 ]
[ 1383677-45-9 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 3384 - 3387

43
[ 2033-24-1 ]
[ 4052-30-6 ]
[ 1404448-94-7 ]

Yield	Reaction Conditions	Operation in experiment
74%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;	Step 1. 2,2-Dimethyl-5-(4-(methylsulfonyl)benzoyl)-1,3-dioxane-4,6-dione A solution of 4-(methylsulfonyl)benzoic acid (2 g, 9.99 mmol, 1.00 equiv), 2,2-dimethyl-1,3-dioxane-4,6-dione (1.72 g, 11.93 mmol, 1.20 equiv), 4-dimethylaminopyridine (1.82 g, 14.92 mmol, 1.50 equiv), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC HCl) (2.5 g, 13.02 mmol, 1.30 equiv) in dichloromethane (50 mL) was stirred overnight at room temperature. The resulting solution was diluted with 100 mL of DCM and washed with 3100 mL of HCl (1N) and then 3100 mL of brine. The resulting organic layer was concentrated in vacuo to afford 2.4 g (74%) of 2,2-dimethyl-5-(4-(methylsulfonyl)benzoyl)-1,3-dioxane-4,6-dione as yellow solid.

Reference： [1]Patent: US2012/277224,2012,A1 .Location in patent: Page/Page column 23

44
[ 1093254-29-5 ]
[ 4052-30-6 ]
[ 1093255-44-7 ]

Yield	Reaction Conditions	Operation in experiment
39%	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃;	In a 1 dram vial, 3-[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5- chlorobenzonitrile (25 mg, 0.080 mmol), DIPEA (0.014 mL, 0.080 mmol) and 4- (methylsulfonyl)benzoic acid (16.09 mg, 0.080 mmol) were dissolved in DMF (1 mL). HATU was added (30.6 mg, 0.080 mmol) and the solution stirred overnight. The reaction mixture was diluted to 2 mL with MeOH. Purification was accomplished by Reverse-Phase HPLC (water/acetonitrile with 0.1 % TFA) to afford the title compound (0.016 g, 39%) as a white solid. 1H NMR (400 MHz, Acetone-d6).' delta ppm 8.59 (t, 1 H), 8.1 1 - 8.18 (m, 2 H), 8.00 - 8.07 (m, 2 H), 7.63 (t, 1 H), 7.47 - 7.53 (m, 1 H), 7.41 - 7.45 (m, 1 H), 7.36 - 7.41 (m, 2 H), 4.70 (d, 2 H), 3.16 (s, 3 H). LCMS m/z 494.9 (M+1 ).

Reference： [1]Patent: WO2008/154271,2008,A1 .Location in patent: Page/Page column 109

45
[ 1418026-00-2 ]
[ 4052-30-6 ]
[ 1418024-63-1 ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: Example 1-109 1-Phenyl-1H-pyrazole-4-carboxylic acid [7-fluoro-1-(2-fluoro-phenyl)-4-oxo-1,4-dihydro-quinolin-3-ylmethyl]-amide A mixture of 4-(methanesulfonyl)benzoic acid (50.2 mg, 0.251 mmol), bromo-tris- pyrrolidino-phosphonium hexafluorophosphate (PyBrOP) (140 mg, 0.301 mmol) N,N- diisopropylethylamine (162 mg, 1.25 mmol) and CH2CI2 (10 mL) was stirred at room temperature for 5 min. After this time, 3-aminomethyl-7-chloro-4-oxo- 1 -phenyl- 1,4- dihydro-quinoline-2-carboxylic acid methyl ester hydrochloride (intermediate I) (95 mg, 0.251 mmol) was added. The reaction mixture was stirred at room temperature for 3 hr. The reaction mixture was concentrated and purified by preparative reverse-phase HPLC, providing 7-chloro-3-[(4-methanesulfonyl-benzoylamino)-methyl]-4-oxo-1-phenyl-1,4- dihydro-quin-oline-2-carboxylic acid methyl ester. MS calcd. for C26H22CIN2O6S[(M+H)+] 525.1, obsd. 525.0.

Reference： [1]Patent: WO2013/7676,2013,A1 .Location in patent: Page/Page column 191

46
[ 3537-14-2 ]
[ 4052-30-6 ]
C₁₃H₁₀N₄O₄S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 5896 - 5899

47
[ 30235-26-8 ]
[ 4052-30-6 ]
4-methylsulfonyl-N-[4-(2-pyridinyl)-2-thiazolyl]-benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
32%		General procedure: EDCI (1.7 mmol) was added in small batches to a solution of the carboxylic acid (1.4 mmol) and HOBt (1.7 mmol) in dry DCM or DMF (5 ml), and the reaction mixture was stirred for 10 minutes at room temperature. A solution of the appropriate amine (1.1 mmol) in 5 ml of dry DCM or DMF was added in small portions and the reaction mixture left to stir for 24 hr at room temperature (monitored by TLC until completion). The reaction mixture was then washed with saturated aqueous sodium bicarbonate (3 x 10ml), saturated aqueous sodium chloride (2 x 10ml), dried with anhydrous Na2SO4 and concentrated under reduced pressure. Purification by column silica gel chromatography (EtOAc/Hexane, 40:60) afforded the products as solids

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 560 - 564

48
[ 22821-77-8 ]
[ 5398-77-6 ]
[ 4052-30-6 ]

Reference： [1]Chinese Journal of Chemistry,2014,vol. 32,p. 117 - 122

49
[ 4052-30-6 ]
[ 74-88-4 ]
[ 22821-70-1 ]

Reference： [1]Organic and Biomolecular Chemistry,2014,vol. 12,p. 2114 - 2127

50
[ 14150-95-9 ]
[ 4052-30-6 ]
C₁₃H₁₂N₂O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	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℃;Sealed tube;	General procedure: The appropriate aminopyridine-N-oxide (13, 1.00 equiv) and carboxylic acid/acid chloride (14, 1.20 equiv) were combined in DMF (0.50 M) and treated with i-Pr2EtN (2.5equiv) and HATU (1.2 equiv). The reaction was stirred at r.t.until the initial coupling was deemed complete by LC-MS(usually 1-2 h). The reaction was then treated with tetrahydroxydiboron (5, 2.00 equiv) in a single portion (Note: exotherm evident). After stirring for 10 min, the reaction was quenched with H2O (10 mL), which resulted in the precipitation of most products. The solids were filtered,washed with H2O, and air-dried to afford the desired products in sufficient purity. For those reactions where precipitation of solid was not evident, the desired products were extracted with EtOAc (3 × 10 mL), washed with brine,dried (Na2SO4), and evacuated. These crude materials were purified by silica gel column chromatography.

Reference： [1]Synlett,2013,vol. 24,p. 2695 - 2700

51
[ 79-19-6 ]
[ 4052-30-6 ]
5-(4-(methylsulfonyl)phenyl)-1,3,4-thiadiazol-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%		General procedure: 5.1.1 5-(4-Morpholinophenyl)-1,3,4-thiadiazol-2-amine (59) A mixture of 4-morpholinobenzoic acid (5.18 g, 25 mmol) and N-aminothiourea (2.28 g, 25 mmol) in POCl3 (7 ml) was stirred vigorously at 75 C for 0.5 h. After addition of H2O (30 ml), the reaction mixture was heated under reflux for 4 h and basified to pH 8 by 50% NaOH solution. The mixture was filtered and the filter cake was recrystallized from ethanol to yield 3.90 g of compound 59 as a yellow crystal. Yield: 59%; The synthetic procedures of compounds 60-81 were the same as that described above. 5.1.1.12 5-(4-(Methylsulfonyl)phenyl)-1,3,4-thiadiazol-2-amine (71) Yield: 41%, mp: 241-242 C (EtOH). ESI-MS m/z: 256.1 [M+H]+; 1H NMR (DMSO-d6) delta 3.26 (s, 3H), 7.65 (s, 2H), 7.99-8.02 (m, 4H).
200 mg	With trichlorophosphate; at 80℃; for 0.75h;	A mixture of 4-(methylsulfonyl)benzoic acid (200 mg, 1 mmol) and thiosemicarbazide (92 mg, 1 mmol) in phosphorous(V) oxychloride was heated to 80C for 45 minutes. The reaction mixture was cooled and water (5 ml) was added slowly (exothermic reaction). The reaction mixture was cooled and pH was adjusted to pH 7. The product was filtered and the solid was washed with water and dried to give 200 mg of the title compound as a solid. (0300) LC-MS (ES): 255.9 (M+H), 1H NMR (400 MHz, DMSO-d6) delta 8.00 (dd, 4H), 7.63 (s, 2H), 3.25 (s, 3H).

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 5766 - 5775
[2]Patent: WO2017/186893,2017,A1 .Location in patent: Page/Page column 39-40

52
[ 695-84-1 ]
[ 4052-30-6 ]
2,3-dihydrobenzofuran-3-yl 4-(methylsulfonyl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide; In 1,2-dichloro-ethane; at 60℃; for 6h;	The reaction flask was charged with Bu4NI (0.2 mmol, 74 mg)Compound 1a (2.8 mmol, 336 mg),Compound 2 g (2 mmol, 304 mg), t-BuOOH (412 muL), 1,2-dichloroethane (4.0 mL). The system was then heated in air at 60 C for about 6 hours, quenched with saturated sodium sulfite solution, extracted with ethyl acetate (40 mL x 3)The solvent was removed by rotary evaporator and adsorbed on silica gel. The product was purified by a simple column chromatography to yield 3 g of product in 88% yield.

Reference： [1]Patent: CN105130933,2017,B .Location in patent: Paragraph 0053-0055
[2]Journal of Organic Chemistry,2015,vol. 80,p. 10734 - 10741

53
[ 4052-30-6 ]
[ 343788-69-2 ]
tert-butyl 4-methyl-4-(4-(methylsulfonyl)benzamido)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With triethylamine; HATU; In dichloromethane; at 20℃; for 2h;	ieri-Butyl-4-methyl-4-(4-(methylsulfonyl)benzamido)piperidine-1-carboxylate To a stirred solution of 4-(methylsulfonyl)benzoic acid (200 mg, 1 mmol) in dichloromethane (20 mL) was added ferf-butyl 4-amino-4-methylpiperidine-1 -carboxylate (214 mg, 1 mmol), 1 - [bis(dimethylamino)methylene]-1 -/-1 ,2,3-triazolo[4,5-b]pyridinium-3-oxide hexafluorophosphate (HATU) (380 mg, 1 mmol) and triethylamine (0.202 g, 2 mmol). The resulting mixture was stirred for 2 hours at room temperature before the reaction was quenched with water (20 mL). The aqueous layer was extracted with ethyl acetate (2 chi 30 mL) and the combined organic layers were concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluting with ethyl acetate : petroleum ether = 1 :1 to afford ferf-butyl-4-methyl-4-(4-(methylsulfonyl)benzamido)piperidine-1 - carboxylate (0.3 g, 75%) as a colorless oil. LCMS (ESI): m/z = 397.2 [M+H] +.

Reference： [1]Patent: WO2015/175171,2015,A1 .Location in patent: Page/Page column 77

54
4-(5-(4-(benzyloxy)phenyl)-1H-imidazol-1-yl)piperidine [ No CAS ]
[ 4052-30-6 ]
4-(1-(1-(4-(methylsulfonyl)benzoyl)piperidin-4-yl)-1H-imidazol-5-yl)phenyl 3-cyanobenzenesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76.9%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20℃; for 2h;	Finally,The intermediate (30.0 mg, 0.07 mmol)And TEA (12.3 [mu] L, 0.09 mmol)Dissolve in dry dichloromethane (5 mL)4- (Methylsulfonyl) benzoic acid (18.0 mg, 0.09 mmol) And EDC HCl (17.3 mg, 0.09 mmol)Solution.After stirring at room temperature for 2 hours, the residue was diluted with saturated aqueous NH4CI (5 mL) and extracted with dichloromethane (3 x 5 mL). The organics were dried under MgSO4, filtered and concentrated in vacuo. The resultant was purified by silica gel chromatography (CHCl3: MeOH = 40: 1) to give 13a (31.8 mg, 76.9% yield)

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 7410 - 7430
[2]Patent: KR2017/85170,2017,A .Location in patent: Paragraph 0239; 0240

55
C₂₂H₂₄N₄O₄S [ No CAS ]
[ 4052-30-6 ]
4-(1-(1-(4-(methylsulfonyl)benzoyl)piperidin-4-yl)-1H-imidazol-5-yl)phenyl 3-(methylcarbamoyl)benzenesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72.8%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20℃; for 2h;	Finally,The intermediate (30.0 mg, 0.07 mmol)And TEA (12. 5 mul, 0. 09 mmol) Dissolve in dry dichloromethane (5 mL)To this mixture was added 4- (methylsulfonyl) benzoic acid (20.2 mg, 0.09 mmol) And EDCmHCl (17.3 mg, 0.09 mmol). After stirring at room temperature for 2 hours, the residue was diluted with saturated aqueous NH4Cl (5 mL) and extracted with dichloromethane (3 x 5 mL). The organics were dried under MgSO4, filtered and concentrated in vacuo. The result was purified by silica gel chromatography (CHCl3: MeOH = 40: 1) to give compound 13e (30.8 mg, 72.8% yield)

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 7410 - 7430
[2]Patent: KR2017/85170,2017,A .Location in patent: Paragraph 0239; 0240

56
4-(1-(piperidin-4-yl)-1H-imidazol-5-yl)phenyl 3-(cyclopropylcarbamoyl)benzenesulfonate [ No CAS ]
[ 4052-30-6 ]
4-(1-(1-(4-(methylsulfonyl)benzoyl)piperidin-4-yl)-1H-imidazol-5-yl)phenyl 3-(cyclopropylcarbamoyl)benzenesulfonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66.9%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; at 20℃; for 2h;	Following,Finally, the intermediate (30.0 mg, 0.06 mmol) and TEA (5.67 L, 0.08 mmol) was dissolved in dry dichloromethane (5 mL), and a solution of 4- (methylsulfonyl) benzoic acid (16.0 mg, 0.08 mmol) and EDCHCl (15.3 mg, 0.08 mmol) . After stirring at room temperature for 2 hours,The residue was diluted with saturated aqueous NH4Cl (5 mL) and extracted with dichloromethane (3 x 5 mL).The organics were dried under MgSO4, filtered and concentrated in vacuo. The resultant was purified by silica gel chromatography (CHCl3: MeOH = 40: 1) to obtain Compound 13e (26.1 mg, 66.9% yield)

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 7410 - 7430
[2]Patent: KR2017/85170,2017,A .Location in patent: Paragraph 0263; 0264

57
[ 123-30-8 ]
[ 4052-30-6 ]
N-(4-hydroxyphenyl)-4-(methylsulfonyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%		General procedure: (1.30 g, 6.49 mmol) of 4-(Methylsulfonyl)benzoic acid (1a) was mixed with (4.67 g, 2.83 mL, 38.9 mmol) of thionyl chloride in anhydrous THF (7 mL) under argon in a 48 mL HW pressure vessel. After sonication in water bath at 65 C for 75-90 min. the solvent was reduced under vacuum, dry ether was added under argon, followed by removing the solvent again under vacuum. The resulted product was dissolved in anhydrous THF (5 mL) and added slowly to a mixture, in ice bath, of triethylamine (1.97 g, 1.40 mL, 19.5 mmol) and 4-substituted aniline 2a (0.779 g, 7.14 mmol), 2b (0.880 g, 7.14 mmol), 2c (0.980 g, 7.14 mmol), under argon. After stirring for 24 h at r. t., solvent was removed under vacuum and the crude solid was sonicated with a mixture of diethyl ether and THF (9:1) (50 mL) followed by suction filtration and additional wash with Et2O (2 x 50 mL) to offer the desired amide in a pure form 3a? (1.55 g, 5.32 mmol, 82%), 3b? (1.59 g, 5.19 mmol, 80%), and 3c? (1.76 g, 5.52 mmol, 85%).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 4757 - 4762

58
[ 623-04-1 ]
[ 4052-30-6 ]
N-(4-(hydroxymethyl)phenyl)-4-(methylsulfonyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%		General procedure: (1.30 g, 6.49 mmol) of 4-(Methylsulfonyl)benzoic acid (1a) was mixed with (4.67 g, 2.83 mL, 38.9 mmol) of thionyl chloride in anhydrous THF (7 mL) under argon in a 48 mL HW pressure vessel. After sonication in water bath at 65 C for 75-90 min. the solvent was reduced under vacuum, dry ether was added under argon, followed by removing the solvent again under vacuum. The resulted product was dissolved in anhydrous THF (5 mL) and added slowly to a mixture, in ice bath, of triethylamine (1.97 g, 1.40 mL, 19.5 mmol) and 4-substituted aniline 2a (0.779 g, 7.14 mmol), 2b (0.880 g, 7.14 mmol), 2c (0.980 g, 7.14 mmol), under argon. After stirring for 24 h at r. t., solvent was removed under vacuum and the crude solid was sonicated with a mixture of diethyl ether and THF (9:1) (50 mL) followed by suction filtration and additional wash with Et2O (2 x 50 mL) to offer the desired amide in a pure form 3a? (1.55 g, 5.32 mmol, 82%), 3b? (1.59 g, 5.19 mmol, 80%), and 3c? (1.76 g, 5.52 mmol, 85%).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 4757 - 4762

59
[ 4052-30-6 ]
[ 104-10-9 ]
N-(4-(2-hydroxyethyl)phenyl)-4-(methylsulfonyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%		General procedure: (1.30 g, 6.49 mmol) of 4-(Methylsulfonyl)benzoic acid (1a) was mixed with (4.67 g, 2.83 mL, 38.9 mmol) of thionyl chloride in anhydrous THF (7 mL) under argon in a 48 mL HW pressure vessel. After sonication in water bath at 65 C for 75-90 min. the solvent was reduced under vacuum, dry ether was added under argon, followed by removing the solvent again under vacuum. The resulted product was dissolved in anhydrous THF (5 mL) and added slowly to a mixture, in ice bath, of triethylamine (1.97 g, 1.40 mL, 19.5 mmol) and 4-substituted aniline 2a (0.779 g, 7.14 mmol), 2b (0.880 g, 7.14 mmol), 2c (0.980 g, 7.14 mmol), under argon. After stirring for 24 h at r. t., solvent was removed under vacuum and the crude solid was sonicated with a mixture of diethyl ether and THF (9:1) (50 mL) followed by suction filtration and additional wash with Et2O (2 x 50 mL) to offer the desired amide in a pure form 3a? (1.55 g, 5.32 mmol, 82%), 3b? (1.59 g, 5.19 mmol, 80%), and 3c? (1.76 g, 5.52 mmol, 85%).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 4757 - 4762

60
[ 623-73-4 ]
[ 110-67-8 ]
[ 4052-30-6 ]
ethyl N-(3-methoxypropanoyl)-N-(4-(methylsulfonyl)benzoyl)glycinate [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2016,vol. 14,p. 10723 - 10732

61
1-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-(2-amino-2-methylpropanamido)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl) 3-benzyl (1R,3S)-2,2-dimethylcyclobutane-1,3-dicarboxylate [ No CAS ]
[ 4052-30-6 ]
1-benzyl 3-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-3a-(2-methyl-2-(4-(methylsulfonyl)benzamido)-2-methylpropanamido)-2-oxo-2,3,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl) (1R,3S)-2,2-dimethylcyclobutane-1,3-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60.97%		To a stirred solution of 4-(methylsulfonyl)benzoic acid (0.778 g, 3.889 mmol, 3.0 eq) in DMF (10 ml) was added HBTU (1.475 g, 3.889 mmol, 3.0 eq) followed by triethylamine (1.08 ml, 7.776 mmol, 6.0 eq). The reaction mixture was stirred at room temperature for about 30 minutes then 1 -((3 aR, 5 aR,5bR, 73^,9^, 1 laR, l lbR, 13a,S)-3a-(2-amino-2-methyl propanamido)-l-isopropyl-5a,5b,8,8,l la-pentamethyl-2-oxo-3,3a,4,5,5a,5b,6,7,7a,8,9,10, l l, 1 la, l lb, 12, 13, 13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl) 3-benzyl (lS,3R)-2,2-di methylcyclobutane-1, 3-dicarboxylate (Intermediate 1, 1.0 g, 1.296 mmol, 1.0 eq) was added and stirred at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was diluted with water (120 ml) and extracted with ethyl acetate (2x50 ml). The combined organic extracts were washed with water (70 ml), dried over Na2S04, filtered and evaporated under reduced pressure. The residue was purified by silicagel column chromatography by using 0-2% methanol in dichloromethane gradient. The fractions containing the expected product were combined and concentrated under reduced pressure to obtain the desired product (0.75 g, yield: 60.97%) as a white solid. 1H NMR (300 MHz, CDC13): delta ppm 8.0 (d, J = 6.9 Hz, 2H), 7.96 (d, J = 6.9 Hz, 2H), 7.34 (m, 5H), 7.18 (s, 1H), 6.70 (s, 1H), 5.15, 5.09 (ABq, J^ = 12.3 Hz, 2H), 4.45 (dd, J = 11.1, 4.5 Hz, 1H), 3.22-3.11 (m, 1H), 3.06 (s, 3H), 2.84-2.72 (m, 3H), 2.70-2.60 (m, 2H), 2.38-2.26 (m, 2H), 2.09-1.98 (m, 1H), 1.97-1.83 (m, 3H), 1.72 (brs, 6H), 1.71-1.40 (m, 9H), 1.40-1.29 (m, 2H), 1.34 (s, 3H), 1.27-1.17 (m, 8H), 1.08 (s, 3H), 0.96 (s, 3H), 0.95 (s, 3H), 0.89 (s, 3H), 0.85 (s, 3H), 0.84 (s, 3H), 0.79 (m, 1H); ESI-MS: m/z 976.15 (M+Na)+.

Reference： [1]Patent: WO2016/178092,2016,A2 .Location in patent: Page/Page column 102; 103

62
[ 3185-99-7 ]
[ 5398-77-6 ]
[ 22821-77-8 ]
[ 4052-30-6 ]

Yield	Reaction Conditions	Operation in experiment
		The fresh material added to the primary oxidation reactor was MnO2 dissolved in methyl sulfone toluene and acetic acid And Co(Ac)2*4H2O at a total concentration of 150 ppm and a mass ratio of acetic acid to p-methylsulphenyltoluene of 0.15. When the device was operated at steady state, the flow rate of the fresh p-methylsulphenyl toluene in the oxidation reactor was 9.4 mL / h. The average residence time of the oxidation reactor in liquid phase was 3.5 h, Pure oxygen was continuously introduced into the oxidation reactor, maintaining the reaction temperature at 150 C and the reaction pressure at 1.1MPa. The volume ratio of water added into the hydrolysis reactor to that of the oxidation reaction liquid entering the hydrolysis reactor was 0.42:1, the reaction temperature in the hydrolysis reactor was maintained at 105 C and the reaction pressure was 0.7 MPa. The retention time of liquid phase was 3.5 h. The liquid phase at the outlet of the hydrolysis reactor was continuously fed into a liquid-liquid delaminator at a temperature of 136 C and a pressure of 0.6 MPa. The conversion of p-methylsulphenyl toluene in the system was 97.0%, and the selectivity to p-methylsulfonylbenzyl alcohol, p-methylsulfonylbenzaldehyde and p-methylsulfonylbenzoic acid was 51%.5%, 39.2% and 9.3%, respectively. Other by-products were not detected.

Reference： [1]Patent: CN105237317,2016,A .Location in patent: Paragraph 0071; 0072

63
[ 4052-30-6 ]
[ 603143-27-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: dicyclohexyl-carbodiimide / ethyl acetate / 3 h / 20 °C / Inert atmosphere 2: pyridine; caesium carbonate / ethyl acetate / 30 h / 35 °C / Inert atmosphere; Irradiation
	Multi-step reaction with 2 steps 1: dmap; dicyclohexyl-carbodiimide / 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran / 2 h / 20 °C / Schlenk technique; Inert atmosphere 2: isonicotinate tert-butyl ester / 24 h / 110 °C / Schlenk technique; Inert atmosphere

Reference： [1]Candish, Lisa; Teders, Michael; Glorius, Frank [Journal of the American Chemical Society, 2017, vol. 139, # 22, p. 7440 - 7443]
[2]Cheng, Wan-Min; Shang, Rui; Zhao, Bin; Xing, Wei-Long; Fu, Yao [Organic Letters, 2017, vol. 19, # 16, p. 4291 - 4294]

64
[ 85342-65-0 ]
[ 4052-30-6 ]
4,5,6,7-tetrachloro-1,3-dioxoisoindolin-2-yl 4-(methylsulfonyl)benzoate [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2017,vol. 139,p. 7440 - 7443

65
[ 524-38-9 ]
[ 4052-30-6 ]
1,3-dioxoisoindolin-2-yl 4-(methylsulfonyl)benzoate [ No CAS ]

Reference： [1]Organic Letters,2017,vol. 19,p. 4291 - 4294

66
[ 4052-30-6 ]
[ 53250-83-2 ]

Reference： [1]Journal of Organic Chemistry,2017,vol. 82,p. 8716 - 8724

67
(1-(3-aminophenyl)piperidin-4-yl)(4-methylpiperazin-1-yl)methanone [ No CAS ]
[ 4052-30-6 ]
N-(3-(4-(4-methylpiperazine-1-carbonyl)piperidin-1-yl)phenyl)-4-(methylsulfonyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37%	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; ethyl acetate; at 20℃; for 20h;	General procedure: 4 (0.1 g, 0.0002 mol), 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxidhexafluorophosphate (HATU, 0.2 g, 0.0004 mol), and substituted benzoic acid (0.0003 mol) weredissolved in 2 mL of dichloromethane followed by DIPEA (1 g, 0.7 mmol), the reaction was allowed toreact at room temperature for 20 h, 20 mL of methylene chloride was added, and the reaction solutionwas washed with saturated sodium bicarbonate solution (10 mL x 2). The reaction solution was driedover anhydrous sodium sulfate and evaporated to dryness under reduced pressure to give a yellowoil which was purified by column chromatography on silica gel (n-hexane:ethyl acetate = 10:1) to getproduct 5a-q.

Reference： [1]Molecules,2018,vol. 23

68
ethyl 2-(N-tert-butoxycarboxamido)-4-(methylsulfonylbenzamide)acetate [ No CAS ]
ethyl 2-((tert-butoxycarbonyl)amino)-3-(4-(methylsulfonyl)phenyl)-3-oxopropanoate [ No CAS ]
[ 4052-30-6 ]

Yield	Reaction Conditions	Operation in experiment
27.1 g; 4.5 g	With potassium tert-butylate; In tetrahydrofuran; at 0 - 10℃; for 2h;Inert atmosphere;	A solution of t-BuOK (14.4 g, 0.13 mol) in THF (150 mL) was added to a solution of crude 9 (38.0 g, 0.1 mol) in THF (200 mL) at 0 C dropwise over 1 h under N2. After aging at 0-10 C for 1 h, then adjusted to pH7 with 10% citric acid, and the organic layer was washed with brine (50 mL x 3), the combined organic layers were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Recrystallized from MTBE afforded 5 (27.1 g, 71%, over three steps) as a colorless solid. Mp 100.6-102.7 C. FTIR (ATR): nu 3354, 2982, 2931, 1736, 1680, 1511, 1278, 1149, 1004, 961, 777, 728. 1H NMR (400 MHz, CDCl3): delta 8.30 (d, J=8.0 Hz, 2H), 8.08 (d, J=8.0 Hz, 2H), 5.89 (dd, J=6.8 Hz,17.6 Hz, 2H), 4.20 (q, 2H), 3.10 (s, 3H),1.45 (s, 9H), 1.16 (t, J=7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3): delta 192.7, 167.3, 155.9, 146.0, 139.6, 131.2, 128.8, 82.0, 63.8, 60.7, 45.3, 29.2, 14.9. HRMS (ESI) calcd for C17H23NNaO7S [M+Na]+ 408.1093, found 408.1086. After the aqueous phase was adjusted to pH 2-3 with 1 N aqueous HCl, the white precipitate was collected by filtration to afford the starting material 6 (4.5 g, 23%) as a white crude solid, mp 265-268 C (lit.13 mp 264-265 C).

Reference： [1]Tetrahedron,2016,vol. 72,p. 1787 - 1793

69
(2S,4S)-N-(4-(2-amino-2-oxoacetyl)tetrahydro-2H-pyran-4-yl)-1-((R)-2-amino-3-cyclohexylpropanoyl)-4-(5-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)pyrrolidine-2-carboxamide monohydrochloride [ No CAS ]
[ 4052-30-6 ]
(2S,4S)-N-(4-(2-amino-2-oxoacetyl)tetrahydro-2H-pyran-4-yl)-1-((R)-3-cyclohexyl-2-(4-(methylsulfonyl)benzamido)propanoyl)-4-(5-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)pyrrolidine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; HATU; In dichloromethane; N,N-dimethyl-formamide; at 23℃; for 18h;	To a mixture of 4-(methylsulfonyl)benzoic acid (Combi-Blocks, CA, catalog* OR-0048) (659 mg, 3.29 mmol), Intermediate J (1.6 g, 2.74 mmol) and HATU (1.46 g, 3.84 mmol) in DMF (6 mL) and DCM (16 mL) was added /Pr2EtN (52 y , 0.3 mmol) and the reaction mixture was stirred at 23 C for 18 hours. The mixture was partitioned between EtOAc (100 mL) and sat. aq. NaHCC (100 mL) and the aqueous layer was extracted with EtOAc (3 x 100 mL). The combined extracts were washed with brine (100 mL), dried over MgS04, filtered and concentrated under reduced pressure. This residue was purified by column chromatography using a RediSep Gold cartridge (120 g, silica gel) eluting with a 0-12.5% MeOH in DCM gradient. The desired fractions were concentrated under reduced pressure to provide the title compound as a white solid. MS (ESI+): 730

Reference： [1]Patent: WO2017/222915,2017,A1 .Location in patent: Paragraph 0259-0260

70
benzyl (7-amino-5-((3S)-2-((R)-2-amino-3-cyclohexylpropanoyl)-2-azabicyclo[2.2.1]heptane-3-carboxamido)-6-hydroxy-7-oxoheptyl)carbamate hydrochloride [ No CAS ]
[ 4052-30-6 ]
benzyl (7-amino-5-((3S)-2-((R)-3-cyclohexyl-2-(4-(methylsulfonyl)benzamido)propanoyl)-2-azabicyclo[2.2.1]heptane-3-carboxamido)-6-hydroxy-7-oxoheptyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90 mg		[0435] Into a 20 mL sample vial equipped with a magnetic stir bar and under N2 was added 4-(methanesulfonyl)benzoic acid (46 mg, 0.23 mmol, 1.0 equiv), HATU (89 mg, 0.23 mmol, 1.0 equiv), EtN(iPr)2 (161 muL, 0.92 mmol, 4 equiv) and DMF (2 mL). The reaction was stirred at room temperature for 10 minutes at which stage a solution of benzyl (7-amino-5-((3S)-2-((R)-2-amino-3-cyclohexylpropanoyl)-2-azabicyclo[2.2.1]heptane-3- carboxamido)-6-hydroxy-7-oxoheptyl)carbamate hydrochloride (140 mg, 0.23 mmol, 1.0 equiv) in DMF (2 mL) was added. The reaction mixture was stirred at room temperature for 18 h overnight. The reaction mixture was quenched with water (10 mL) and extracted with EtOAc (2 × 20 mL). The combined organic layers were washed with brine (5 mL), dried over MgSO4, filtered and concentrated under reduced pressure. Purification by column chromatography through silica gel (24 g), eluting with 100:0:0 to 70:15:15 Hexanes:CH2Cl2:iPrOH as a gradient afforded the title compound (90 mg).

Reference： [1]Patent: WO2017/222917,2017,A1 .Location in patent: Paragraph 0434; 0435

71
(2S,4S)-1-((R)-2-amino-3-cyclohexylpropanoyl)-N-(1-amino-7-(3-cyclopropylureido)-1,2-dioxoheptan-3-yl)-4-(5-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)pyrrolidine-2-carboxamide hydrochloride [ No CAS ]
[ 4052-30-6 ]
(2S,4S)-N-(1-amino-7-(3-cyclopropylureido)-1,2-dioxoheptan-3-yl)-1-((R)-3-cyclohexyl-2-(4-(methylsulfonyl)benzamido)propanoyl)-4-(5-(2-hydroxypropan-2-yl)-1H-1,2,3-triazol-1-yl)pyrrolidine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
24 mg	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 23℃; for 18h;Inert atmosphere;	[0403] To a round-bottom flask equipped with a magnetic stir bar and under nitrogen was prepared a solution of (2S,4S)-1-((R)-2-amino-3-cyclohexylpropanoyl)-N-(1- amino-7-(3-cyclopropylureido)-1,2-dioxoheptan-3-yl)-4-(5-(2-hydroxypropan-2-yl)-1H- 1,2,3-triazol-1-yl)pyrrolidine-2-carboxamide hydrochloride (Intermediate M, 100 mg, 0.15 mmol, 1.0 equiv), 4-(methylsulfonyl)benzoic acid (30 mg, 0.15 mmol, 1.0 equiv), HATU (68 mg, 0.18 mmol, 1.2 equiv) and DMF (1.0 mL). The solution was treated with drop-wise addition of EtN(iPr)2 (105 muL, 0.6 mmol, 4.0 equiv) and the mixture was stirred at room temperature for 18 h overnight. The reaction mixture was quenched with water (5 mL) and extracted with CH2Cl2 (3 × 5 mL) and the combined organic layers were concentrated under reduced pressure and loaded directly onto a 5 g C18 cartridge. Purification by reverse-phase column chromatography (15 g C18 column + 5 g C18 precartridge), eluting with 100:0 to 60:40 H2O:MeCN + 0.1% HCO2H as a gradient afforded the title compound (24 mg). [0404] 1H NMR (CD3OD, 300 MHz): delta 8.12-7.85 (4H, m), 7.48-7.45 (1H, m), 5.85-5.76 (1H, m), 5.11-5.03 (1H, m), 4.67-4.38 (1H, m), 4.20-4.05 (2H, m), 3.11 (3H, s), 3.15-2.86 (4H, m), 2.24-2.18 (1H, m), 1.98-0.34 (30H, m) ppm. MS (ESI+) 814 (M+1) ^

Reference： [1]Patent: WO2017/222917,2017,A1 .Location in patent: Paragraph 0403; 0404

72
[ 55424-42-5 ]
[ 4052-30-6 ]
[ 36198-15-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine / N,N-dimethyl-formamide 2: trifluoroacetic acid

Reference： [1]Current Patent Assignee: SPARAMEDICA; ROCHE HOLDING AG - DE2135713, 1972, A1 [Chem.Abstr., 1972, vol. 76, # 140794][Chem.Abstr., 1972, vol. 76, # 140794]

73
[ 331959-40-1 ]
[ 4052-30-6 ]
3-methyl-5-(4-(methylsulfonyl)benzamido)-N₂-phenylthiophene-2,4-dicarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%		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.

Reference： [1]European Journal of Medicinal Chemistry,2019,vol. 164,p. 179 - 192

74
[ 124-38-9 ]
4-(methylsulfonyl)phenyl sulfurofluoridate [ No CAS ]
[ 4052-30-6 ]

Reference： [1]Organic Letters,2019,vol. 21,p. 2464 - 2467

75
[ 4052-30-6 ]
[ 64984-08-3 ]

Yield	Reaction Conditions	Operation in experiment
80%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; 1-iodo-butane; N,N,N',N'-tetramethyl-1,8-diaminonaphthalene; chloro-N,N,N',N'-bis(tetramethylene)formamidinium hexafluorophosphate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In toluene at 120℃; for 16h; Sealed tube; Inert atmosphere;
	Multi-step reaction with 2 steps 1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 20 °C / Inert atmosphere; Schlenk technique 2: [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis{3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC}iridium(III) hexafluorophosphate; Chloroiodomethane / ethyl acetate / 12 h / Schlenk technique; Inert atmosphere; Irradiation

Reference： [1]Boehm, Philip; Cacherat, Bastien; Lee, Yong Ho; Martini, Tristano; Morandi, Bill [Angewandte Chemie - International Edition, 2021, vol. 60, # 31, p. 17211 - 17217][Angew. Chem., 2021, vol. 133, # 31, p. 17348 - 17355]
[2]Patra, Tuhin; Mukherjee, Satobhisha; Ma, Jiajia; Strieth-Kalthoff, Felix; Glorius, Frank [Angewandte Chemie - International Edition, 2019, vol. 58, # 31, p. 10514 - 10520][Angew. Chem., 2019, vol. 131, p. 10624 - 10630,7]

76
(2S)-2-amino-4-methylsulfanyl-N-(4-phenylthiazol-2-yl)butanamide [ No CAS ]
[ 4052-30-6 ]
N-[(1S)-3-methylsulfanyl-1-[(4-phenylthiazol-2-yl)carbamoyl]propyl]-4-methylsulfonylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of <strong>[4052-30-6]4-methylsulfonylbenzoic acid</strong> (23.75 mg, 1 18.64 pmol) in DCM (3 ml_) was added DIPEA (46.00 mg, 355.91 pmol) and HATU (49.62 mg, 130.50 pmol). The mixture was stirred at 30 for 10 min. (2S)-2-amino-4-methylsulfanyl-N-(4-phenylthiazol-2-yl)butanamide (50 mg, 1 18.64 pmol) was added and the reaction mixture was stirred at 30C for 2 hr. The reaction mixture was concentrated to dryness to give a residue. The residue was purified by prep-HPLC (column: Phenomenex Synergi C18 1502510 pm; mobile phase: [water(0.1 %TFA)-ACN]; B%: 45%-69%, 12 min) and lyophilized to afford compound 68 as a white solid. 1 H NMR (400 MHz, METHANOL-d4) d = 8.19-8.05 (m, 4H), 7.92 (d, J= 7.2 Hz, 2H), 7.42-7.39 (m, 3H), 7.33-7.31 (m, 1 H), 4.97-4.94 (m, 1 H), 3.19 (s, 3H), 2.73-2.66 (m, 2H), 2.33-2.24 (m, 2H), 2.16 (s, 3H) ppm. LCMS (ESI) m/z: [M+H]+=490.1 .

Reference： [1]Patent: WO2019/152437,2019,A1 .Location in patent: Page/Page column 150

77
(Z)-N'-hydroxy-4-(((4-methyl-2-oxo-2H-chromen-7-yl)oxy)methyl)benzimidamide [ No CAS ]
[ 4052-30-6 ]
4-methyl-7-((4-(5-(4-(methylsulfonyl)phenyl)-1,2,4-oxadiazol-3-yl)benzyl)oxy)-2H-chromen-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49.2%		General procedure: To a solution of substituted carboxylic acid (0.5 mmol) in a mixed solvent of N,Ndiisopropylethylamine(110 mul, 0.55 mmol) and CH2Cl2 (5 ml) was added HATU (209 mg,0.55 mmol). The reaction mixture was stirred for 3 h at room temperature, transferredvia pipet, and added dropwise to a stirred solution of intermediate 4 (162 mg, 0.5 mmol)in CH2Cl2 (5 ml). The reaction was stirred 3 h and concentrated under reduced pressure. Ethyl acetate (15 ml) was added to the resulting residue, followed by washing with H2O(30 ml) and then brine (30 ml). The organic layer was concentrated. The resulting residue and NaOAc (29 mg, 4 mmol) were dissolved in EtOH (10 ml). The reaction mixture was refluxed overnight and then concentrated. The residue was purified by silica gel column chromatography to afford corresponding target compounds 5a-5x.

Reference： [1]Journal of Asian Natural Products Research,2019,vol. 21,p. 1090 - 1103

78
[ 1517-05-1 ]
[ 4052-30-6 ]
2-azidoethyl 4-(methylsulfonyl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane;Inert atmosphere;	A mixtureof acid derivative (1 eq.), 2-azidoethanol 12 (1.5 eq.), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride(EDC) (2 eq.), and dimethylamino pyridine (DMAP)(1.5 eq.) in 6 ml of DCM was put on stirrer under argon andthe reaction was left overnight. )en, the reaction was dilutedwith 70 ml DCM and washed with 50 ml 1M HCl. )eorganic layer was collected and evaporated under reducedpressure. )e remaining crude was puri7ed by Bash chromatographyon silica gel. (14a). Following the general procedure for esteri7cationreaction, 4-(methylsulfonyl) benzoicacid 13a (150 mg,0.75 mmol), 2-azidoethanol 12 (98 mg, 1.125 mmol), EDC(287.55 mg, 1.5 mmol), and DMAP (138.0 mg, 1.125 mmol)in 6 ml DCM were used. )en, the crude product was puri7ed using Bash chromatography with a mobile phase ofHexane : EtOAc (1 : 1). A pure white solid product was obtained(Yield 69%, 140 mg, 0.52 mmol). Rf: 0.4 (Hexane/EtOAc 1 : 1).1H NMR (500 MHz, DMSO): * 8.17 (d, 2H,J = 7.9 Hz, Ph H-2, Ph H-6), 8.07 (d, 2H, J = 8.2 Hz, Ph H-3,Ph H-5), 4.47 (t, 2H, J = 4.9 Hz, CH2O), 3.67 (t, 2H,J = 5.2 Hz, CH2N3), 3.24 (s, 3H, SO2CH3). 13C NMR(125 MHz, DMSO): * 164.9, 145.4, 134.1, 130.6, 128.0, 64.8,49.8, 43.7.

Reference： [1]Journal of Chemistry,2020,vol. 2020

79
[ 3482-49-3 ]
[ 4052-30-6 ]
3-((4-(methylsulfonyl)benzoyl)oxy)fusidic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 25℃;Inert atmosphere;	General procedure: The respective carboxylic acid (4.0 eq.), DCC (4.0 eq.) and DMAP (0.4 eq.) were added to a solution of FA (1.0 eq.) in anhydrous DCM. The reaction mixture was stirred at 25 C under N2 atmosphere. After completion of reaction (TLC), the reaction mixture was diluted with EtOAc, filtered and washed with 2 N HCl, saturated aqueous NaHCO3, brine and water. The organic layer was then dried over anhydrous MgSO4, filtered and concentrated in vacuo. The crude product was then purified by column chromatography on silica gel to afford the corresponding target compound.

Reference： [1]Bioorganic and Medicinal Chemistry,2020,vol. 28

80
[ 4393-16-2 ]
[ 4052-30-6 ]

Yield	Reaction Conditions	Operation in experiment
78%	With tert.-butylhydroperoxide; sodium chloride; sodium hydroxide In water monomer at 90℃; for 8h; Green chemistry;	General procedure for the synthesis of 4-methoxy benzoicacid from 4-methoxy benzylamines General procedure: A 50 mL of round bottom flask was charged with a magneticbead,0.1 g (0.729 mmol) of 4- methoxy benzyl amine, 0.0084 g ofNaCl (20 mol%), 0.116 g of NaOH (4 equiv) and 0.336 g of aq. TBHP (5equiv) in 0.3 mL of deionised H2O and it was heated at 90 C for 8 h. Afterwards, the reaction mixture was neutralized by aq. HCl and extracted with EtOAc. The organic layer was dried over anhydrousNa2SO4 and after evaporation of the solvent, the crude mixture waspurified by the silica gel column chromatography with EtOAc:Hexane (06:94 v/v) as eluent. 4-methoxy benzoic acid was obtainedin 84% yield (93 mg).
	Multi-step reaction with 2 steps 1: 4-phenylnaphthalene-1,2-dione; N,N,N-tributyl-1-butanaminium iodide / acetonitrile; water monomer / 24 h / 80 °C 2: tert.-butylhydroperoxide / water monomer / 24 h / 80 °C

Reference： [1]Jaiswal, Arvind Kumar; Kushawaha, Ajay Kishor; Pandey, Shubham; Sashidhara, Koneni V. [Tetrahedron, 2021]
[2]Kim, Hun Young; Oh, Kyungsoo; Si, Tengda [Chemistry - A European Journal, 2021, vol. 27, # 72, p. 18150 - 18155]

81
[ 4052-30-6 ]
[ 18107-18-1 ]
[ 22821-70-1 ]

Yield	Reaction Conditions	Operation in experiment
81.4 mg	In methanol; benzene at 20℃; for 4h;	16 Example 16: Preparation of Compound III-10 At room temperature, p-methylsulfonyltoluene (85.1 mg, 0.5 mmol) was dissolved in acetonitrile (1.5 mL) and 1 M aqueous hydrochloric acid (1.5 mL), TBADT (33.0 mg, 0.01 mmol) was added, followed by the reaction The system was connected to an oxygen balloon, and the reaction system was placed under a 2×3W purple LED lamp and stirred for 24 hours. After the reaction of the raw materials was completed, the solvent was removed under reduced pressure to obtain a crude product.The crude product was dissolved in benzene (2.4 mL) and methanol (0.6 mL), TMSCHN2(171.33 mg, 1.5 mmol) was added, stirred at room temperature for 4 hours, and the reaction system was adjusted to Vpetroleum ether/Vethyl acetate=10 : 1 column chromatography to obtain 81.4 mg of III-10 target product with a yield of 76%.

Reference： [1]Current Patent Assignee: UNIV CENTRAL CHINA NORMAL - CN114057569, 2022, A Location in patent: Paragraph 0100-0103

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

CAS No. :	4052-30-6	MDL No. :	MFCD00007564
Formula :	C₈H₈O₄S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	AJBWNNKDUMXZLM-UHFFFAOYSA-N
M.W :	200.21	Pubchem ID :	77670
Synonyms :

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.12
Num. rotatable bonds :	2
Num. H-bond acceptors :	4.0
Num. H-bond donors :	1.0
Molar Refractivity :	46.5
TPSA :	79.82 Å²

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.05 cm/s

Log Po/w (iLOGP) :	0.92
Log Po/w (XLOGP3) :	0.67
Log Po/w (WLOGP) :	1.87
Log Po/w (MLOGP) :	1.11
Log Po/w (SILICOS-IT) :	0.53
Consensus Log Po/w :	1.02

[ CAS No. 4052-30-6 ] {[proInfo.proName]}

Quality Control of [ 4052-30-6 ]

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Product Details of [ 4052-30-6 ]

Calculated chemistry of [ 4052-30-6 ]

Physicochemical Properties

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Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 4052-30-6 ]

Application In Synthesis of [ 4052-30-6 ]

[ 4052-30-6 ] Synthesis Path-Upstream 1~2

[ 4052-30-6 ] Synthesis Path-Downstream 1~81

Related Functional Groups of
[ 4052-30-6 ]

Aryls

Carboxylic Acids

Sulfones

Precautionary Statements-General

Prevention

Response

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Disposal

Physical hazards

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Environmental hazards

Inquiry

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

Log S (ESOL) :	-1.71
Solubility :	3.88 mg/ml ; 0.0194 mol/l
Class :	Very soluble
Log S (Ali) :	-1.92
Solubility :	2.39 mg/ml ; 0.0119 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.09
Solubility :	1.63 mg/ml ; 0.00817 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.5

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302	Packing Group:	N/A
GHS Pictogram:

Precautionary Statements-General
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Code	Phrase
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P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
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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.
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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

[ CAS No. 4052-30-6 ] {[proInfo.proName]}

Quality Control of [ 4052-30-6 ]

Related Doc. of [ 4052-30-6 ]

Product Details of [ 4052-30-6 ]

Calculated chemistry of [ 4052-30-6 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 4052-30-6 ]

Application In Synthesis of [ 4052-30-6 ]

[ 4052-30-6 ] Synthesis Path-Upstream 1~2

[ 4052-30-6 ] Synthesis Path-Downstream 1~81

Related Functional Groups of [ 4052-30-6 ]

Aryls

Carboxylic Acids

Sulfones

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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[ 4052-30-6 ]