Name: 14316-16-6|N-(2-Aminoethyl)-4-methylbenzenesulfonamide|95%
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SKU: A103957
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1
[ 2362-45-0 ]
[ 14316-16-6 ]
[ 14316-17-7 ]

Yield	Reaction Conditions	Operation in experiment
	(i) tBuCOCl, Py, CHCl₃, (ii) /BRN= 612776/; Multistep reaction;

Reference： [1]Zaoral,M. et al. [Collection of Czechoslovak Chemical Communications, 1967, vol. 32, # 2, p. 843 - 853]

2
[ 3634-89-7 ]
[ 14316-16-6 ]
[ 77429-97-1 ]

Yield	Reaction Conditions	Operation in experiment
77%	In acetonitrile Heating;
71%	In acetonitrile Heating;
70%	In acetonitrile for 15h; Heating;

Reference： [1]Martin, Andrea E.; Ford, Thomas M.; Bulkowski, John E. [Journal of Organic Chemistry, 1982, vol. 47, # 3, p. 412 - 415]
[2]Zhang, Zhibo; Mikkola, Satu; Loennberg, Harri [Organic and Biomolecular Chemistry, 2003, vol. 1, # 5, p. 854 - 858]
[3]Padayachy; Fernandes; Marques; De Sousa [Journal of Chemical Crystallography, 2008, vol. 38, # 8, p. 577 - 582]
[4]Martin, Andrea E.; Bulkowski, John E. [Journal of the American Chemical Society, 1982, vol. 104, # 5, p. 1434 - 1436] Gu, Kun-Jian; Bowman-James, Kristin [Tetrahedron Letters, 1995, vol. 36, # 12, p. 1977 - 1980]

3
[ 3634-89-7 ]
[ 14316-16-6 ]

Yield	Reaction Conditions	Operation in experiment
94%	With ammonia In ethanol at 18 - 25℃; for 5h;
	Multi-step reaction with 2 steps 1: 95 percent / TMSN₃; TBAF / tetrahydrofuran / 12 h / 20 °C 2: 94 percent / H₂ / Pd/C / methanol / 20 h / 20 °C

Reference： [1]Baranov, S. V.; Mochalin V. B. [Journal of Organic Chemistry USSR (English Translation), 1981, vol. 17, p. 951 - 953][Zhurnal Organicheskoi Khimii, 1981, vol. 17, # 5, p. 1077 - 1080]
[2]Wu, Jie; Hou, Xue-Long; Dai, Li-Xin [Journal of Organic Chemistry, 2000, vol. 65, # 5, p. 1344 - 1348]

4
[ 107-15-3 ]
[ 98-59-9 ]
[ 14316-16-6 ]

Yield	Reaction Conditions	Operation in experiment
95%	With zinc oxide-nanoparticle at 50℃; for 1h; Neat (no solvent); chemoselective reaction;
85%	In dichloromethane at 20℃; for 3h;
83%	With triethylamine In dichloromethane at 20℃; for 12h;	1.1 (1) Synthesis of N-(2-aminoethyl)-4-methylphenyl-1-sulfonamide: Ethylenediamine (10 mmol) was dissolved in 10 mL of dichloromethane, and a solution of 30 mmol of triethylamine and 10 mL of dichloromethane containing 4-toluenesulfonyl chloride (7.5 mmol) was added at room temperature under stirring at room temperature. Stir for 12 hours, then add 50 mL of dichloromethane, and wash 2-3 times with 15% potassium hydrogencarbonate solution and ultrapure water, separate the organic phase, distill off the organic solvent under reduced pressure, separate by column chromatography, rinse The reagent is petroleum ether/dichloromethane (V/V=50:1-10:1), and the compound N-(2-aminoethyl)-4-methylphenyl-1-sulfonamide (1) is obtained. yield : 83%.

83%	In dichloromethane at 40℃; for 0.25h;	1.1; 2.1; 3.1; 4.1; 5.1 Step 1: Under stirring conditions, evenly disperse 4-toluenesulfonyl chloride (1.90g 10mmol) and ethylenediamine (6.0g 100mmol) in the solvent dichloromethane (25mL), heat the reaction at 40°C for 15 minutes and then cool to room temperature . The obtained substituted product mixture was washed twice with distilled water (25 mL), dried over sodium sulfate and then revolved to remove the solvent to obtain a white solid product with a yield of 83% (1.78 g). Named as compound 1.
83%	In dichloromethane at 20℃; for 6h;	Compound 6 A solution of toluene sulfonyl chloride (10 mmol, 1.90 g) in CH2Cl2(25 mL) was added slowly to a stirred solution of ethylenediamine (100 mmol, 6.00 g) in CH2Cl2(25 mL). After being stirred at room temperature for 6 h, the mixture was washed twice with water (25 mL) and dried over Na2SO4. The solvent was removed in vacuo to obtain a white solid product. Yield: 1.78 g, 83%.1H NMR (400 MHz, CDCl3-d) δ 7.78 - 7.71 (m, 2H), 7.33 - 7.27 (m, 2H), 3.01 - 2.88 (m, 2H), 2.78 (dd,J= 6.6, 4.7 Hz, 2H), 2.42 (s, 3H).
81%	With triethylamine In dichloromethane at 20℃; for 2h; Inert atmosphere;
81%	With triethylamine In dichloromethane at 20℃; for 2h; Inert atmosphere;
80%	In dichloromethane; 1,2-dichloro-ethane at 0℃; for 1h;	23.1 (1)According to the method of step (1) in Preparation 1,the difference is,Ethylenediamine (20 mmol) was used instead of (R, R) -1,2-diphenyl-ethylenediamine,And the reaction at 0 1h,Thus, 14.6 mmol of the diamine derivative represented by Formula 3-9 was obtained,The yield was 80%.
79%	In dichloromethane at 20℃; for 2h;	4.4. The synthesis of 3b The ethylenediamine (1.500 g, 25 mmol) was dissolved inCH2Cl2 (100 ml). TsCl (0.953 g, 5 mmol) in CH2Cl2 (20 ml)was addeddropwise over 2 h. The reaction stirred at room temperatureovernight. The reaction was monitored by TLC. After the reactionwas completed, the mixturewas concentrated under reduced press.The residue was purified by column chromatography using CH2Cl2:MeOH 10:1(v/v) as eluent. The product was isolated as a whitesolid. Yield: 846 mg, 79.0%. 1H NMR (400 MHz, CDCl3) δ 7.76 (d,J = 7.4 Hz, 2H), 7.27 (d, J =7.6 Hz, 2H), 4.80 (s, 3H), 3.04 (d,J = 4.6 Hz, 2H), 3.01-2.91 (m, 2H), 2.39 (s, 3H).
79%	In dichloromethane at 20℃; Cooling with ice;	1 Synthesis of compound 3b First, ethylene diamine (1.500 g, 25 mmol) was dissolved in 100 ml of CH2Cl2. Then, p-toluenesulfonyl chloride (0.953 g, 5 mmol) was dissolved in dichloromethane under ice-water bath conditions using a constant-pressure dropping funnel and slowly added dropwise to the reaction system.The reaction was stirred at room temperature overnight. The reaction was monitored by TLC.After the reaction was completed, the mixture was concentrated under reduced pressure to remove the solvent.Finally, take CH2Cl2: MeOH (10: 1 v / v)Further separation and purification by silica gel column chromatography as an eluent gave a white viscous solid846 mg.The yield was 79.0%.
77%	With triethylamine In dichloromethane at 0 - 20℃;	4.2 General procedure for preparation of ethylenediamine and propylenediamine sulfonamides 3a-t General procedure: To a solution of proper diamine 1a,b (10 mmol) in dichloromethane (20 mL), triethylamine (300 mg, 0.416 mL, 30 mmol) was added with stirring. The mixture was cooled to 0 °C, and a solution of the appropriate sulfonyl chloride 2a-j (5 mmol) in dichloromethane (2 mL) was added dropwise. The mixture stirred at room temperature overnight. The reaction mixture was washed with 10% Na2CO3 (20 mL) and then with distilled water (3×15mL). The organic layer separated and dried over anhydrous Na2SO4. The solvent was evaporated under reduced pressure, and the residue was purified flash column chromatography (silica gel, appropriate ratio of hexanes-ethyl acetate) to give the purified semisolid compounds 3a-t.
76%	In dichloromethane for 0.25h;
76%	In dichloromethane for 0.25h;	A mixture of p-toluenesulfonyl chloride (1.91 g, 10 mmol) in dichloromethane (25 mL) was slowly added to a stirred solution of ethylenediamine (6.0 g, 100 mmol) in dichloromethane (25 mL). The resulting mixture was stirred for another 15 min, washed twice with distilled water (25 mL) and dried over CaH2. The solvent was removed in vacuo to give a fine white powder (1.62 g, 7.6 mmol, 76%). 1H-NMR (400 MHz, CDCl3, 330K): δ 2.42 (s, 3H); 2.79 (m, 2H); 2.94 (m, 2H); 7.30 (d, 2H, J = 8.3 Hz); 7.75 (d, 2H, J = 8.3 Hz).
75%	With cesium hydroxide In N,N-dimethyl-formamide at 0℃; for 2h;
75%	With cesium hydroxide; 4 A molecular sieve In N,N-dimethyl-formamide at 0℃; for 2h;
75.2%	In chloroform at 18℃; for 2h; Inert atmosphere;	N-(2-Aminoethyl)-4-methylbenzenesulfonamide (2). A solution of 15.00 g (78.74 mmol) of 4-toluenesulfonylchloride in 45 mL of chloroform was addeddropwise with stirring at 18°C under dry nitrogen to asolution of 23.62 g (393.70 mmol) of ethylenediamine.The mixture was stirred for 2 h, washed with distilledwater to remove ethylenediamine hydrochloride andexcess ethylenediamine, dried over MgSO4, filtered,and evaporated under reduced pressure. Yield 75.2%, white powder. IR spectrum, ν, cm-1: 3363 (N-H,amine), 3288 (N-H, amide), 3049 (C-Harom), 2975-2885 (CH3, CH2); 1596, 1492, 1440 (C=Carom); 1458-1439, 1404-1364 [δ(CH3), δ(CH2)]; 1315-1288, 1146(SO2); 1186, 1044, 1018 [δ(C-Harom)], 1062 (C-N,amine), 922 (S-N), 814 [δ(C-Harom)]. 1H NMR spectrum,δ, ppm: 2.37 m (3H, CH3), 2.49-2.53 m (2H,CH2NH2), 2.69-2.72 m (2H, SO2NHCH2), 3.72 m(3H, NH2, SO2NH), 7.36-7.40 m (2H, C6H4), 7.61-7.69 m (2H, C6H4).
74%	In benzene for 3h;
74%	With triethylamine In dichloromethane at 0℃;
73%	In dichloromethane at 0 - 20℃; for 10h;	General procedure for the synthesis of N-sulfonamides 7 General procedure: To a solution of the corresponding sulfonyl chloride (26.0 mmol)in 26 mL of dichloromethane at 0 °C, was added rapidly propane-1,3-diamine or (rac)-cyclohexane-1,2-diamine (10 eq., 3 M). Themixturewas allowed to reach roomtemperature andwas stirred during10 h. The crude mixture was filtered and the obtained oil was concentratedunder reduced pressure. Then, 10 mL of ice-water were addedto the concentrated mixture and a solid appeared which was filtrated and washed with cool water and dried under vacuum for 12 h.
72%	In toluene at 40℃; Reflux;	1 Example 1 Synthesis of compound N - (2-aminoethyl) -4-methylbenzenesulfonamide (3):. In a 25 mL round bottom flask,Ethylenediamine (1) 1 mmol, 1 mmol) was slowly added to toluene (5 mL) at 40 ° C,With full stirring p-toluenesulfonyl chloride (2) 1.0 mmol,Heated to reflux for 3 - 4 h, cooled to room temperature,To the reaction, 5 ml of 1 M aqueous HCl solution was added,Remove the filter residue by suction filtration,The filtrate was neutralized with NaOH to precipitate a large amount of white solid,Vacuum filtration, solid vacuum drying,Solid N - (2-aminoethyl) -4-methylbenzenesulfonamide (3) was obtained.Yield: 72%. The product is not purified,Direct the next reaction.
70%	In dichloromethane at 0 - 20℃;
70.6%	In dichloromethane at 40℃; for 1.5h;
63%	Stage #1: ethylenediamine With triethylamine In dichloromethane at 0℃; for 0.166667h; Stage #2: p-toluenesulfonyl chloride In dichloromethane at 20℃;	1 Synthesis of compound N-(2-aminoethyl)-4-methylbenzenesulfonamide (3) : At 0 °C, a 100 mL round bottom flask was charged with 10 mmol of ethylenediamine (1) and 20 mL of methylene chloride, with stirring, 30 mmol of triethylamine, after the resulting solution was stirred for 10 min, a further 5 mmol of p-toluenesulfonyl chloride (2) in dichloromethane (3 mL) was added dropwise. Then warmed to room temperature and stirred for 10-12 hours. The reaction was then quenched by adding 20 mL of 10% aqueous sodium carbonate solution to the reaction, additional 20 mL of dichloromethane was added to the reaction system, After the whole reaction system was washed with water three times, the organic phase is dried over anhydrous magnesium sulphate. The dichloromethane was distilled off under reduced pressure to give a crude white powder which was purified by column chromatography (petroleum ether / methylene chloride = 50: 1 to 10: 1), recrystallization from ethanol gave the product as a white solid N-(2-aminoethyl)-4-methylbenzenesulfonamide (3). Yield: 63%.
63%	In dichloromethane at 20℃; for 12h;
60%	In dichloromethane at 20℃; for 6h;
59%	With triethylamine In tetrahydrofuran; dichloromethane at 20℃; for 2h;	N-(2-Aminoethyl)-4-methylbenzenesulfonamide N-(2-Aminoethyl)-4-methylbenzenesulfonamide 1,2-Diaminoethane(2.0 g, 33 mmol) and triethylamine (6.7 g,75 mmol) were dissolved in a 2/1 solvent mixture of CH2Cl2/THF(50 mL). The resulting solution was stirred at room temperature and4-methylbenzenesulfonyl chloride (3.2 g, 17 mmol) was added portion-wise over 2h. The reaction was quenched by addition of 1 M HCl (50 mL). The biphasicmixture was extracted with 1 M HCl (20 mL x 2). The combined aqueous layerswere basified with 2 M NaOH (50 mL) and extracted with CH2Cl2 (50 mL x 3). The organic layerswere combined, dried (MgSO4), filtered and concentrated under reducedpressure to give a colourless solid (2.1 g, 59% yield) suitably pure forsubsequent synthetic steps. Mpt: Decomposed before melting; Rf =0.22 (15% MeOH in CH2Cl2);IR (νmax/cm-1, thin film): 3360, 2644, 1598, 1493, 1317; 1H NMR (600 MHz, CD3OD):δH= 2.42 (s, 3H, CH3), 2.65 (t, J = 6.2 Hz, 2H, 8-H),2.89 (t, J = 6.2 Hz, 2H, 7-H), 7.38 (d, J = 8.2 Hz, 2H, 3-Hand 5-H), 7.73 (d, J = 8.2 Hz, 2H, 2-H and 6-H); 13CNMR (150 MHz, CD3OD): δC =21.4 (CH3), 42.2 (C-8), 46.4 (C-7),128.0 (C-2 and C-6), 130.8 (C-3 andC-5), 138.8 (C-1),144.7 (C-4); HRMS m/z (EI+): Found 215.08564 [M+ H]+; C9H15O2N3Srequires 215.08542.
58%	With triethylamine In tetrahydrofuran; dichloromethane at 20℃; for 2h;	19.1 Step 1A/-(2-aminoethyl)-4-methylbenzenesulfonamide (8TP27)1 ,2-Diaminoethane (2.0 g, 33 mmol) and triethylamine (6.7 g, 66 mmol) were dissolved in a 2/1 solvent mixture of CH2CI2/THF (50 mL). The resulting solution was stirred at room temperature and 4-methylbenzenesulfonyl chloride (3.2 g, 17 mmol) was added portion-wise over 2 h. The reaction was quenched by addition of 1 M HCI (50 mL). The biphasic mixture was extracted with 1 M HCI (20 mL x 2). The combined aqueous layers were basified with 2 M NaOH (50 mL) and extracted with CH2CI2 (50 mL x 3). The organic layers were combined, dried (MgS04), filtered and concentrated in vacuo to give a colourless solid (2.1 g, 58% yield) suitably pure for subsequent synthetic steps. Rf = 0.22 (15% MeOH in CH2CI2); 1H NMR (600 MHz, CD3OD): δΗ = 2.42 (s, 3H, CH3), 2.65 (t, J = 6.2 Hz, 2H, CH2NH2), 2.89 (t, J = 6.2 Hz, 2H, NHCH2), 7.38 (d, J = 8.2 Hz, 2H, 3-H and 5-H), 7.73 (d, J = 8.2 Hz, 2H, 2-H and 6-H); 13C NMR (150 MHz, CD3OD): 5c = 21.4 (CH3), 42.2 (CH2NH2), 46.4 (NHCH2), 128.0 (C-2 and C-6), 130.8 (C-3 and C-5), 138.8 (C-1 ), 144.7 (C-4);
57%	In pyridine at -13℃; for 2h;
53.9%	In dichloromethane for 1h;
	In dichloromethane for 12h; Ambient temperature;
	In dichloromethane for 0.25h;	4.2. General procedure for synthesis of mono-N-sulfonated ethylenediamines General procedure: A solution of sulfonyl chloride (10 mmol) in CH2Cl2 (25 mL) was slowly added to a stirred solution of ethylenediamine (6.0 g, 100 mmol) in dry CH2Cl2 (25 mL). The resulting mixture was stirred for 15 min, washed twice with water (25 mL) and dried over Na2SO4. The solvent was removed in vacuo and the monosulfonylated ethylenediamine was obtained after flash chromatography (CH2Cl2/methanol).
	With triethylamine In dichloromethane at 0 - 20℃;
	In dichloromethane at 20℃; Cooling with ice; Inert atmosphere;	1.1 (1) 3 g of 4-methylbenzenesulfonyl chloride (15.8 mmol) was dissolved in 8 mL of dichloromethane, was added dropwise to 9.48 g of ethylenediamine (158 mmol) under ice-cooling and nitrogen protection, the resulting mixed solution was stirred at room temperature overnight. After completion of the reaction, the reaction mixture was extracted three times with dichloromethane and potassium carbonate aqueous solution, the organic phase was collected, adding magnesium sulfate and drying, filtered; the resulting solid was purified by column chromatography over silica gel using dichloromethane / methanol as the eluent and V / V = 8: 1, the organic solvent was removed by rotary evaporation, to give solid N-(2-aminoethyl)-4-methylbenzenesulfonamide. (...) The above obtained N-(2-aminoethyl)-4-methylbenzenesulfonamide solid (430 mg, 2 mmol) with 4-bromo-1,8-naphthalic anhydride (554 mg, 2 mmol) was dissolved in 20 mL of ethanol, stirring to make it completely dissolved; the resulting solution was heated to 85 ° C under stirring conditions for 18h; after cooling to room temperature, filtered, N-[2-(6-bromo-1H-benzo(de)isoquinolin-1,3(2H)-dion-2-yl)-ethyl]-4-methylbenzenesulfonamide was obtained.
	In dichloromethane at 0℃; for 4h;	General procedure for the preparation of unsaturated amide 2.1h To a solution of ethylenediamine (30.0 g, 498.3 mmol) in dry CH2Cl2 (125 mL) wasadded slowly p-toluenesulfonyl chloride (9.5 g, 49.8 mmol) in dry CH2Cl2 (125 mL) at 0°C. The reaction mixture was stirred for 4 h. The resulting solution was concentrated andwashed with water (50 mL × 2), dried over anhydrous Na2SO4 and KOH pellets, filteredand evaporated in vacuo to obtain crude amine 2.5h.
	With MC at 0 - 20℃; for 18h;
	In dichloromethane at 20℃; for 3h;
	With triethylamine In dichloromethane at 0 - 20℃; for 18h;	4.1.1. General procedure for synthesis of N-(2-aminoethyl and 3-aminopropyl)unsubstituted and substituted phenyl sulfonamide (3a-p) General procedure: A solution of appropriate sulfonyl chloride (2a-h, 5 mmol) in dichloromethane (2 mL) was added dropwise to a solution of properdiamine (1a,b, 10 mmol) and trimethylamine (300 mg, 30 mmol) in dichloromethane (20 mL) at 0 °C. The reaction mixture was allowed to stir at rt for 18 h. The reaction mixture was washed with saturated solution of NaHCO3 (20 mL). The organic layer was dried over anhydrous sodium sulfate and evaporated under vacuum to give the titled products 3a-p [27].
	With triethylamine In dichloromethane at 0 - 20℃;	4.1.1. General procedure for synthesis of N-(2-aminoethyl and 3-aminopropyl)unsubstituted and substituted phenyl sulfonamide (3a-h and 4a-h): General procedure: A solution of appropriate sulfonyl chloride (2a-h, 5 mmol) in dichloromethane(2 ml) was added dropwise to a solution of properdiamine (1a,b, 10 mmol) and trimethylamine (300 mg, 30 mmol) indichloromethane (20 ml) at 0 °C. The reaction mixture was allowed tostir at rt for 18 h. The reaction mixture was washed with saturatedsolution of NaHCO3 (20 ml). The organic layer was dried over anhydrous sodium sulfate and evaporated under vacuum to give the titled products 3a-h and 4a-h [30].
	In dichloromethane at 0 - 20℃;	1.2.1. General procedure for synthesis of N-(2-aminoethyl and 3-aminopropyl)unsubstituted and substitutedphenyl sulfonamide (3a-p): General procedure: A solution of appropriate sulfonyl chloride (2a-h, 5 mmol) in dichloromethane (2 ml) was added dropwise to a solutionof proper diamine (1a,b, 10 mmol) and trimethylamine (300 mg, 30 mmol) in dichloromethane (20 ml) at 0 °C. Thereaction mixture was allowed to stir at rt for 18 h. The reaction mixture was washed with saturated solution of NaHCO3(20 ml). The organic layer was dried over anhydrous sodium sulfate and evaporated under vacuum to give the titledproducts 3a-p.
	With triethylamine In dichloromethane at 0 - 20℃; for 4h;	General procedure for preparation of sulfonamide EA derivatives General procedure: The synthesis of the key intermediates compounds 2(a-i), 3(a-i) as well as 4(a-i) were achieved following the previously reported procedures. Ethylene diamine sulfonyl 2(a-i) and piperaziene sulfonyl 3(a-i) were prepared according to references 48-53, while, the 4-aminopiperidine-1-sulfonyl 4(a-i) were prepared according to reference 55. To a solution of 1,2-diaminoethane or piperazine (5.00 mmol) in dichloromethane (10 mL), triethylamine (1.51 g, 2 mL, 15.00 mmol) were added with stirring. The mixture was cooled to 0°C and a solution of the appropriate sulfonyl chloride (2.50 mmol) in dichloromethane (2 mL) was added dropwise. The mixture was stirred at room temperature for 4 hours. The reaction mixture was washed with 20 mL saturated aqueous solution of NaHCO3 and the organic layer was extracted with ethyl acetate (3x 20mL), dried over magnesium sulfate and concentrated under reduced pressure to give the desired intermediates 2(a-i) and 3(a-i). For the synthesis of intermediates 4(a-i), a solution of 4-(N-Boc) aminopiperidine (0.10 g, 0.50 mmol) in dichloromethane (10 mL) and triethylamine (0.15 g, 0.2 mL, 1.50 mmol) was added at 0°C. Then, a solution of sulfonyl chloride (0.50 mmol) in dichloromethane (2 mL) was added in small portions. The reaction was stirred for 4 hours, then, the reaction mixture was quenched with 20 mL of a saturated aqueous solution of NaHCO3. The aqueous layer was extracted with ethyl acetate (3x 20mL), dried over magnesium sulfate and concentrated under reduced pressure. The crude product was dissolved in solution (5 mL) of HCl in dioxane at room temperature for 1h. All solvents were removed under reduced pressure, which gave the corresponding crude salt. The intermediates 2(a-i), 3(a-i) and 4(a-i) were used in the next step directly without further purification. To a solution of EDC (0.62 g, 0.39 mmol), HOBt (0.60 g, 0.39 mmol) and ethacrynic acid (0.10 g, 0.33 mmol) in dry DMF (5 mL) at 0°C, crude amine (2(a-i) or 3(a-i)) was added. In the case of the intermediates 4(a-i), 0.30 mmol of triethylamine was used and the solution was stirred at room temperature. The reaction was monitored by TLC until all the amine was consumed. The mixture was diluted with ethyl acetate (100 mL) and extracted (3x 20mL). The organic phase was washed with water (2 × 50 mL) and brine (3 × 50 mL), dried over anhydrous MgSO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography. 2-(2,3-Dichloro-4-(2-methylenebutanoyl)phenoxy)-N-(2-((4-methylphenyl)sulfonamido)ethyl)acetamide (5a) Following general procedure, the crude residue was purified by silica gel column chromatography, using DCM/EtOAc, 3:1 (v/v) as eluent, Rf =0.50 (3/1. DCM/EtOAc), to furnish 5a as a white solid (98 mg, yield of 60%), m.p. 170-171°C.1H NMR (CDCl3; 400 MHz), δ (ppm): 7.70 (d, J = 8.6 Hz, 2H), 7.25 (d, J = 8.6 Hz, 2H), 7.18-7.12 (m, 2H), 6.84 (d, J= 9.0 Hz, 1H), 5.90 (s, 1H), 5.62-5.58 (m, 2H), 4.51 (s, 2H), 3.47 (q, J= 6.0 Hz, 2H), 3.13 (q, J= 6.0 Hz, 2H), 2.45 (q, J= 7.4 Hz, 2H), 2.36 (s, 3H), 1.13 (t, J= 7.4 Hz, 3H). 13C NMR (CDCl3, 101 MHz); δ (ppm):195.62, 167.92, 154.52, 150.12, 143.56, 136.77, 134.16 131.38, 129.77, 128.86, 127.21, 126.98, 123.05, 111.06, 68.17, 42.89, 38.99, 23.40, 21.47, 12.39. IR (neat): ν = 3401 (NH), 1666 (C=O), 1634 (C=C) cm-1. HRMS (+ESI) m/z: [M+H]+ calculated for C22H24Cl2N2O5S: 499.0855, found, 499.0857
	In dichloromethane at 20℃;
	With triethylamine In dichloromethane at 0 - 20℃; for 2.2h;	1.2 (2) Dissolve p-toluenesulfonyl chloride, ethylenediamine, and triethylamine in a dichloromethane solution at a molar ratio of 1:3:1 at 0°C; then stir at room temperature for 2 hours; then wash with water to remove impurities, The organic phase was collected and dried in vacuum to obtain compound 2 as a white powder.

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[14]Salvatore; Schmidt; Shin; Nagle; Worrell; Jung [Tetrahedron Letters, 2000, vol. 41, # 50, p. 9705 - 9708]
[15]Salvatore, Ralph Nicholas; Nagle, Advait S.; Kyung, Woon Jung [Journal of Organic Chemistry, 2002, vol. 67, # 3, p. 674 - 683]
[16]Gataulina; Kutyrev; Maksimov; Ernandes; Kutyreva [Russian Journal of General Chemistry, 2018, vol. 88, # 11, p. 2300 - 2306][Zh. Obshch. Khim., 2018, vol. 88, # 11, p. 1822 - 1829,8]
[17]Barros, M. Teresa; Siñeriz, Fernando [Tetrahedron, 2000, vol. 56, # 27, p. 4759 - 4764]
[18]Abdel-Maksoud, Mohammed S.; El-Gamal, Mohammed I.; Lee, Bong S.; Gamal El-Din, Mahmoud M.; Jeon, Hong R.; Kwon, Dow; Ammar, Usama M.; Mersal, Karim I.; Ali, Eslam M. H.; Lee, Kyung-Tae; Yoo, Kyung Ho; Han, Dong Keun; Lee, Jae Kyun; Kim, Garam; Choi, Hong Seok; Kwon, Young Jik; Lee, Kwan Hyi; Oh, Chang Hyun [Journal of Medicinal Chemistry, 2021, vol. 64, # 10, p. 6877 - 6901]
[19]Del Solar, Virginia; Quiñones-Lombraña, Adolfo; Cabrera, Silvia; Padrón, José M.; Ríos-Luci, Carla; Alvarez-Valdés, Amparo; Navarro-Ranninger, Carmen; Alemán, José [Journal of Inorganic Biochemistry, 2013, vol. 127, p. 128 - 140]
[20]Current Patent Assignee: UNIVERSITY OF JINAN (SHANDONG) - CN106518762, 2017, A Location in patent: Paragraph 0017; 0018
[21]Li, Xuefeng; Li, Liangchun; Tang, Yuanfu; Zhong, Ling; Cun, Linfeng; Zhu, Jin; Liao, Jian; Deng, Jingen [Journal of Organic Chemistry, 2010, vol. 75, # 9, p. 2981 - 2988]
[22]Ji, Xiuru; Li, Shan; Sun, Lu; Tu, Xiaoqiang; Xi, Zhen; Yang, Chao; Ye, Haishun; Yi, Long [Organic and Biomolecular Chemistry, 2021, vol. 19, # 29, p. 6527 - 6533]
[23]Current Patent Assignee: UNIVERSITY OF JINAN (SHANDONG) - CN107298654, 2017, A Location in patent: Paragraph 0017
[24]Xu, An; Tang, Yonghe; Lin, Weiying [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2018, vol. 204, p. 770 - 776]
[25]Joseph, Kiran; Tikdari, Ahmad M; Mukerjee, Arya K [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1997, vol. 36, # 2, p. 182 - 184]
[26]Sayer, James R.; Walldn, Karin; Pesnot, Thomas; Campbell, Frederick; Gane, Paul J.; Simone, Michela; Koss, Hans; Buelens, Floris; Boyle, Timothy P.; Selwood, David L.; Waksman, Gabriel; Tabor, Alethea B. [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 22, p. 6459 - 6470]
[27]Current Patent Assignee: UNIVERSITY OF LONDON - WO2012/168733, 2012, A1 Location in patent: Page/Page column 101
[28]Zhang, Zhibo; Mikkola, Satu; Loennberg, Harri [Organic and Biomolecular Chemistry, 2003, vol. 1, # 5, p. 854 - 858]
[29]Chen, Feng; Soldevila-Barreda, Joan J.; Romero-Canelón, Isolda; Coverdale, James P. C.; Song, Ji-Inn; Clarkson, Guy J.; Kasparkova, Jana; Habtemariam, Abraha; Brabec, Viktor; Wolny, Juliusz A.; Schünemann, Volker; Sadler, Peter J. [Dalton Transactions, 2018, vol. 47, # 21, p. 7178 - 7189]
[30]Okawara, Tadashi; Uchiyama, Koichi; Okamoto, Yoshinari; Yamasaki, Tetsuo; Furukawa, Mitsuru [Journal of Chemical Research, Miniprint, 1992, p. 2035 - 2048]
[31]Location in patent: experimental part Tan, Jing; Tang, Weijun; Sun, Yawei; Jiang, Zhen; Chen, Fei; Xu, Lijin; Fan, Qinghua; Xiao, Jianliang [Tetrahedron, 2011, vol. 67, # 34, p. 6206 - 6213]
[32]Gamal El-Din, Mahmoud M.; El-Gamal, Mohammed I.; Abdel-Maksoud, Mohammed S.; Yoo, Kyung Ho; Baek, Daejin; Choi, Jungseung; Lee, Huiseong; Oh, Chang-Hyun [Journal of Enzyme Inhibition and Medicinal Chemistry, 2016, vol. 31, p. 111 - 122]
[33]Current Patent Assignee: SOUTH CHINA UNIVERSITY OF TECHNOLOGY - CN106117139, 2016, A Location in patent: Paragraph 0043
[34]Lo, Kai-Yip; Ye, Liu; Yang, Dan [Synlett, 2017, vol. 28, # 13, p. 1570 - 1575]
[35]Abdel-Maksoud, Mohammed S.; Ammar, Usama M.; Oh, Chang-Hyun [Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 10, p. 2041 - 2051]
[36]Polat, Dilan E.; Brzezinski, David D.; Beauchemin, André M. [Organic Letters, 2019, vol. 21, # 12, p. 4849 - 4852]
[37]Abdel-Maksoud, Mohammed S.; Ammar, Usama M.; El-Gamal, Mohammed I.; Gamal El-Din, Mahmoud M.; Mersal, Karim I.; Ali, Eslam M.H.; Yoo, Kyung Ho; Lee, Kyung-Tae; Oh, Chang-Hyun [Bioorganic Chemistry, 2019, vol. 93]
[38]Abdel-Maksoud, Mohammed S.; Ali, Eslam M. H.; Ammar, Usama M.; Ho Yoo, Kyung; Mersal, Karim I.; Oh, Chang-Hyun [Bioorganic Chemistry, 2020, vol. 100]
[39]Ammar, Usama M.; Abdel-Maksoud, Mohammed S.; Mersal, Karim I.; Ali, Eslam M.H.; Yoo, Kyung Ho; Choi, Hong Seok; Lee, Jae Kyun; Cha, Sun Young; Oh, Chang-Hyun [Bioorganic and Medicinal Chemistry Letters, 2020, vol. 30, # 20]
[40]Bignon, Jérôme; El Abbouchi, Abdelmoula; El Brahmi, Nabil; El Kazzouli, Saïd; Guillaumet, Gérald; Hiebel, Marie-Aude; Suzenet, Franck [Bioorganic and medicinal chemistry letters, 2020, vol. 30, # 19]
[41]Kong, Xiuqi; Lin, Weiying; Tang, Yonghe; Zhang, Yunyan [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2021, vol. 247]
[42]Current Patent Assignee: SHANDONG UNIVERSITY - CN113416163, 2021, A Location in patent: Paragraph 0024-0025; 0031-0032

5
[ 107-13-1 ]
[ 14316-16-6 ]
[ 294676-95-2 ]

Yield	Reaction Conditions	Operation in experiment
93%	In acetonitrile for 3h; Heating;
	In ethanol for 6h; Heating;

Reference： [1]Barros, M. Teresa; Siñeriz, Fernando [Tetrahedron, 2000, vol. 56, # 27, p. 4759 - 4764]
[2]Okawara, Tadashi; Uchiyama, Koichi; Okamoto, Yoshinari; Yamasaki, Tetsuo; Furukawa, Mitsuru [Journal of the Chemical Society. Chemical communications, 1990, # 20, p. 1385 - 1386]
[3]Okawara, Tadashi; Uchiyama, Koichi; Okamoto, Yoshinari; Yamasaki, Tetsuo; Furukawa, Mitsuru [Journal of Chemical Research, Miniprint, 1992, p. 2035 - 2048]

6
[ 108-31-6 ]
[ 14316-16-6 ]
N-(2-maleimidoethyl)toluene-4-sulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With cobalt naphthenate; acetic anhydride In N,N-dimethyl acetamide at 70 - 80℃; for 2h;

Reference： [1]Corrie, John E. T. [Journal of the Chemical Society. Perkin transactions I, 1994, # 20, p. 2975 - 2982]

7
[ 15159-40-7 ]
[ 14316-16-6 ]
Morpholine-4-carboxylic acid [2-(toluene-4-sulfonylamino)-ethyl]-amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With triethylamine In 1,4-dioxane at 20℃;

Reference： [1]Luk'yanov, O. A.; Pokhvisneva, G. V.; Ternikova, T. V. [Russian Chemical Bulletin, 1994, vol. 43, # 8, p. 1376 - 1380][Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1994, # 8, p. 1452 - 1456]

8
[ 13939-69-0 ]
[ 14316-16-6 ]
Piperidine-1-carboxylic acid [2-(toluene-4-sulfonylamino)-ethyl]-amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With triethylamine In 1,4-dioxane at 20℃;

Reference： [1]Luk'yanov, O. A.; Pokhvisneva, G. V.; Ternikova, T. V. [Russian Chemical Bulletin, 1994, vol. 43, # 8, p. 1376 - 1380][Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1994, # 8, p. 1452 - 1456]

9
[ 124-63-0 ]
[ 14316-16-6 ]
N-(2-Methanesulfonylamino-ethyl)-4-methyl-benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With triethylamine In 1,4-dioxane at 20℃;

Reference： [1]Luk'yanov, O. A.; Pokhvisneva, G. V.; Ternikova, T. V. [Russian Chemical Bulletin, 1994, vol. 43, # 8, p. 1376 - 1380][Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1994, # 8, p. 1452 - 1456]

10
[ 98-09-9 ]
[ 14316-16-6 ]
N-(2-Benzenesulfonylamino-ethyl)-4-methyl-benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	With triethylamine In 1,4-dioxane at 20℃;

Reference： [1]Luk'yanov, O. A.; Pokhvisneva, G. V.; Ternikova, T. V. [Russian Chemical Bulletin, 1994, vol. 43, # 8, p. 1376 - 1380][Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1994, # 8, p. 1452 - 1456]

11
[ 14316-16-6 ]
[ 98-74-8 ]
C₁₅H₁₇N₃O₆S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With triethylamine In 1,4-dioxane at 20℃;

Reference： [1]Luk'yanov, O. A.; Pokhvisneva, G. V.; Ternikova, T. V. [Russian Chemical Bulletin, 1994, vol. 43, # 8, p. 1376 - 1380][Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1994, # 8, p. 1452 - 1456]

12
[ 14316-16-6 ]
[ 93-11-8 ]
naphthalene-2-sulfonic acid [2-(toluene-4-sulfonylamino)-ethyl]-amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With triethylamine In dichloromethane at 20℃;

Reference： [1]Nyasse, Barthelemy; Grehn, Leif; Maia, Hernani L.S.; Monteiro, Luis S.; Ragnarsson, Ulf [Journal of Organic Chemistry, 1999, vol. 64, # 19, p. 7135 - 7139]

13
[ 261912-63-4 ]
[ 14316-16-6 ]

Yield	Reaction Conditions	Operation in experiment
94%	With hydrogen In methanol at 20℃; for 20h;

Reference： [1]Wu, Jie; Hou, Xue-Long; Dai, Li-Xin [Journal of Organic Chemistry, 2000, vol. 65, # 5, p. 1344 - 1348]

14
[ 78-84-2 ]
[ 14316-16-6 ]
[ 303172-50-1 ]

Yield	Reaction Conditions	Operation in experiment
83%	In ethanol at 20℃; for 1h;
	In acetonitrile at 20℃; for 1h;

Reference： [1]Pokhvisneva; Luk'yanov [Russian Chemical Bulletin, 2000, vol. 49, # 5, p. 894 - 898]
[2]Pokhvisneva; Luk'Yanov [Russian Chemical Bulletin, 2006, vol. 55, # 5, p. 903 - 906]

15
[ 100-10-7 ]
[ 14316-16-6 ]
[ 303172-53-4 ]

Yield	Reaction Conditions	Operation in experiment
83%	In ethanol at 20℃; for 1h;

Reference： [1]Pokhvisneva; Luk'yanov [Russian Chemical Bulletin, 2000, vol. 49, # 5, p. 894 - 898]
[2]Pokhvisneva; Luk'Yanov [Russian Chemical Bulletin, 2006, vol. 55, # 5, p. 903 - 906]

16
[ 100-52-7 ]
[ 14316-16-6 ]
[ 37075-68-6 ]

Yield	Reaction Conditions	Operation in experiment
46%	With borax; sodium tetrahydroborate; sodium tetraborate In ethanol at 20℃; for 2h;

Reference： [1]Squires, Clare; Baxter, Christopher W.; Campbell, John; Lindoy, Leonard F.; McNab, Hamish; Parkin, Andrew; Parsons, Simon; Tasker, Peter A.; Wei, Gang; White, David J. [Dalton Transactions, 2006, # 16, p. 2026 - 2034]

17
[ 123-05-7 ]
[ 14316-16-6 ]
[ 888710-12-1 ]

Yield	Reaction Conditions	Operation in experiment
88%	With borax; sodium tetrahydroborate; sodium tetraborate In ethanol at 20℃;

Reference： [1]Squires, Clare; Baxter, Christopher W.; Campbell, John; Lindoy, Leonard F.; McNab, Hamish; Parkin, Andrew; Parsons, Simon; Tasker, Peter A.; Wei, Gang; White, David J. [Dalton Transactions, 2006, # 16, p. 2026 - 2034]

18
[ 3112-31-0 ]
[ 14316-16-6 ]
3,5-bis[(N-tosylamino)ethylcarbamoyl]pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	Stage #1: 3,5-pyrazoledicarboxylic acid With thionyl chloride In N,N-dimethyl-formamide Stage #2: N-tosylethylenediamine In tetrahydrofuran at 20℃;

Reference： [1]Eisenwiener, Alexander; Neuburger, Markus; Kaden, Thomas A. [Dalton Transactions, 2007, # 2, p. 218 - 233]

19
[ 26663-10-5 ]
[ 14316-16-6 ]
3,5-bis[(N-tosylamino)ethylcarbamoyl]-1H-[1,2,4]triazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: monopotassium salt of 1,2,4-triazole-3,5-dicarboxylic acid With thionyl chloride In N,N-dimethyl-formamide Heating; Stage #2: N-tosylethylenediamine With triethylamine In tetrahydrofuran at 20℃;

Reference： [1]Eisenwiener, Alexander; Neuburger, Markus; Kaden, Thomas A. [Dalton Transactions, 2007, # 2, p. 218 - 233]

20
[ 14316-16-6 ]
[ 22589-46-4 ]
[ 87484-85-3 ]

Yield	Reaction Conditions	Operation in experiment
	With oxalic acid In methanol; acetone	VII Methyl 2-[2-Hydroxy-3-[N-[2-[N-(4-methylphenylsulfonyl)amino]ethyl]amino]propoxy]benzoate Oxalate Methyl 2-[2-Hydroxy-3-[N-[2-[N-(4-methylphenylsulfonyl)amino]ethyl]amino]propoxy]benzoate Oxalate A solution of 2.15 g of N-(2-aminoethyl)-p-toluenesulfonamide (0.1 mole) and 2.08 g of methyl 2-(2,3-epoxypropoxy)benzoate (0.01 mole) in 100 ml of methanol was stored at 25° C. for 4 hours. The methanol was then removed under reduced pressure, leaving an oil (NMR indicated only mono-alkylated product). The oil was then dissolved in 50 ml of methanol and an equimolar quantity of oxalic acid was added to the solution. 50 Ml of acetone was added, and the product crystallized upon refrigeration. The product was recrystallization from acetone/methanol (1:1) to yield 1.4 g of product which had a melting point of 165°-166° C. The elemental analysis (CHN) and NMR spectrum were consistent with the assigned structure.

Reference： [1]Current Patent Assignee: DUPONT DE NEMOURS INC - US4623652, 1986, A

21
[ 108-05-4 ]
(η6-Benzene))ruthenium (II) dichloride [ No CAS ]
[ 14316-16-6 ]
[ 78-79-5 ]
4-methyl-1,5-hexadien-1-yl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
6%	In methanol	3 Synthesis of 4-methylhexa-1,5-dien-1-yl acetate Example 3 Synthesis of 4-methylhexa-1,5-dien-1-yl acetate 4 mg (0.016 mmol) of (η6-benzene) ruthenium (II) dichloride, 15 mg (0.058 mmol) of silver triflate and 11.2 mg (0.052 mmol) of N-2-aminoethyl-p-toluenesulfonamide were placed in a sealed tube, which was then charged with 2 ml (20 mmol) of isoprene, 2 ml (22 mmol) of vinyl acetate and 2 ml of methanol. The mixture was heated with stirring at 100° C. for 6 hours in an argon atmosphere. The reaction mixture was poured into water and the organic layer was concentrated to obtain 0.17 g (yield: 6% based on isoprene) of a co-dimer (4-methylhexa-1,5-dien-1-yl acetate) (Purity: 75%, regioisomer: 17%, cyclic dimer of dienes: 8%).

Reference： [1]Current Patent Assignee: TAKASAGO INTERNATIONAL CORPORATION - US6239324, 2001, B1

22
((tetra-n-butylammonium)6K)-α2-[P2W17O61(Sn(CH2)2CO2H)] [ No CAS ]
[ 14316-16-6 ]
α2-[P2W17O61(Sn(CH2)2CO(monotosyl-ethylenediamine(-H)))](tetra-n-butylammonium)7 [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With CH₃CH₂O(C₉H₆N)CO₂CH₂CH₃ In acetonitrile (TBA6K)(P2W17O61SnCH2CH2COOH) added to soln. of EtO(C9H6N)CO2Et in refluxing MeCN, after 15 min amine added, mixt. refluxed for 96 h; monitored by NMR, filtration, concn. in vacuo, pptn. (acetone/Et2O);
57%	With potassium <i>tert</i>-butylate; isobutyl chloroformate In acetonitrile (TBA6K)(P2W17O61SnCH2CH2COOH) added to suspn. of t-BuOK in MeCN at room temp., after 5 min ClCO2i-Bu slowly added at 0°C, mixt. allowed to warm to room temp. for 30 min., amine added to stirred suspn., stirredfor 1.5 h; monitored by NMR, filtration, concn. in vacuo, pptn. (acetone/Et2O);

Reference： [1]Bareyt, Sebastian; Piligkos, Stergios; Hasenknopf, Bernold; Gouzerh, Pierre; Lacote, Emmanuel; Thorimbert, Serge; Malacria, Max [Journal of the American Chemical Society, 2005, vol. 127, # 18, p. 6788 - 6794]
[2]Bareyt, Sebastian; Piligkos, Stergios; Hasenknopf, Bernold; Gouzerh, Pierre; Lacote, Emmanuel; Thorimbert, Serge; Malacria, Max [Journal of the American Chemical Society, 2005, vol. 127, # 18, p. 6788 - 6794]

23
[ 603956-14-5 ]
[ 14316-16-6 ]
[ 905592-44-1 ]

Yield	Reaction Conditions	Operation in experiment
76%	With triethylamine In dichloromethane at 20℃; for 24h;

Reference： [1]Location in patent: experimental part Masuko, Takashi; Nemoto, Yuta; Kusama, Tadashi; Metori, Koichi; Kizawa, Yasuo; Miyake, Muneharu [Heterocycles, 2009, vol. 78, # 10, p. 2549 - 2558]

24
[ 14316-16-6 ]
[ 906565-55-7 ]
[ 1273236-28-4 ]

Yield	Reaction Conditions	Operation in experiment
49%	Stage #1: N-tosylethylenediamine; 2,4,6-triethylbenzene-1,3,5-tricarbaldehyde at 20℃; for 24h; Stage #2: With sodium tetrahydroborate In methanol for 2h;

Reference： [1]Location in patent: experimental part Cacciarini, Martina; Nativi, Cristina; Norcini, Martina; Staderini, Samuele; Francesconi, Oscar; Roelens, Stefano [Organic and Biomolecular Chemistry, 2011, vol. 9, # 4, p. 1085 - 1091]

25
N-(3-amino-5,6-dichloro-pyrazine-2-carbonyl)guanidine hydrochloride [ No CAS ]
[ 14316-16-6 ]
[ 1345839-27-1 ]

Yield	Reaction Conditions	Operation in experiment
89%	Stage #1: N-(3-amino-5,6-dichloro-pyrazine-2-carbonyl)guanidine hydrochloride; N-tosylethylenediamine In N,N-dimethyl-formamide at 100℃; Stage #2: With hydrogenchloride In water

Reference： [1]Location in patent: scheme or table Matthews, Hayden; Ranson, Marie; Tyndall, Joel D.A.; Kelso, Michael J. [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 22, p. 6760 - 6766]

26
[ 75-15-0 ]
[ 14316-16-6 ]
[ 75483-20-4 ]

Yield	Reaction Conditions	Operation in experiment
60%	With silica gel In water at 20℃; for 12h;	Typical procedure for the synthesis of N-sulfonylcyclothioureas (2a-q) from N-sulfonyldiamines (1a-q) General procedure for N-sulfonylcyclothioureas 2a-g (condition A): To a well-stirred solution of N-sulfonyldiamines (1.5 mmol) in water (5.0 ml) was added silica gel (200-300 mesh, 0.50g) and carbon disulfide (5.0 mmol) at room temperature, and stirring was continued for 12 h. The solid was separated by centrifugation and extracted with acetone (10 ml×3). The mixture was filtered and the combined filtrate was dried over sodium sulfate. The solvent was removed in vacuo and the crude product was purified by column chromatography on silica gel or recrystallization.
58%	Stage #1: carbon disulfide; N-tosylethylenediamine With sodium hydroxide In water at 20℃; for 5h; Stage #2: With sodium monochloroacetic acid In water

Reference： [1]Wan, Guo-Xiang; Xu, Liang; Ma, Xiao-Si; Ma, Ning [Tetrahedron Letters, 2011, vol. 52, # 47, p. 6250 - 6254]
[2]Location in patent: experimental part Wan, Guoxiang; Xu, Liang; Ma, Xiaosi; Zhang, Yong; Wang, Jian; Zhang, Jian; Ma, Ning [Chinese Journal of Chemistry, 2011, vol. 29, # 10, p. 2081 - 2085]

27
C₁₀H₁₆O₃S [ No CAS ]
[ 14316-16-6 ]
[ 1245811-44-2 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In 1,2-dimethoxyethane at 60 - 80℃;	8.2 To a stirred solution of 3-(1,4-cyclohexadien-1-yl)-1-propanol (MW: 138.21; 1.21 g, 9.18 mmol) in 25 mL of DCM 2.7 mL of NEt3 (19.28 mmol) was added and cooled to 0° C. A solution of methane sulfonyl chloride (1.1 mL, 13.8 mmol) was added over a period of 20 min by keeping the internal temperature below 5° C. After 30 min the reaction mixture was allowed to warm up to RT and stirred overnight. The reaction was quenched with saturated NaHCO3 solution. The reaction was worked up with water, brine and dried over Na2SO4. The mesylate derivative (96% yield) was isolated was carried forward to the next step. To a stirred solution of monotosylated ethylenediamine (1.98 g, 9.25 mmol) in 20 mL of 1,2-dimethoxy ethane and NEt3 (2.7 mL, 19.43 mmol) at 60° C. a solution of the mesylate derivative in 10 mL of DME was added slowly over a period of 5 min. Then the solution was heated to 80° C. and stirred overnight. The reaction was quenched with saturated NaHCO3 solution. The reaction was worked up with water, brine and dried over Na2SO4. The desired ligand was isolated by column chromatography with EtOAc as eluent (Rf value 0.1 in EtOAc; visualised with UV @ 254 nm or with basic KMnO4). Isolated yield of the ligand was 1.0 g (33% based on the starting alcohol). 1H NMR: (300 MHz, CDCl3) 7.77-7.73 (2H, m, ArH), 7.32-7.27 (2H, m, ArH), 5.71 (2H, br s, CHCH), 5.34 (2H, br s, CH), 3.04-3.00 (2H, m, CH2NH), 2.82-2.73 (2H, m, CH2NH), 2.72-2.68 (2H, m, -CH2C or CH-CH2-CH), 2.56-2.51 (4H, m, -CH2C or CH-CH2-CH), 2.42 (3H, s, CH3), 1.95-1.90 (2H, m, -NH-CH2-), 1.53-1.48 (2H, m, -CH2-CH2-CH2).
	With triethylamine In 1,2-dimethoxyethane at 59.84 - 79.84℃;

Reference： [1]Current Patent Assignee: JOHNSON MATTHEY PLC - US2012/123142, 2012, A1 Location in patent: Page/Page column 18
[2]Chen, Feng; Romero-Canelón, Isolda; Soldevila-Barreda, Joan J.; Song, Ji-Inn; Coverdale, James P. C.; Clarkson, Guy J.; Kasparkova, Jana; Habtemariam, Abraha; Wills, Martin; Brabec, Viktor; Sadler, Peter J. [Organometallics, 2018, vol. 37, # 10, p. 1555 - 1566]

28
[ 52462-29-0 ]
[ 14316-16-6 ]
[ 208988-63-0 ]

Yield	Reaction Conditions	Operation in experiment
66%	With triethylamine In isopropyl alcohol at 80℃; Inert atmosphere;
36.7%	With triethylamine In isopropyl alcohol Inert atmosphere; Reflux;
	at 20℃; for 0.5h;	1 Example 1 : Production of the catalysts In a 25 mL 2-necked round bottomed flask equipped with thermometer and a magnetic stirrer, 0.020 mmol of metal complex (M(Y)X2]2) and 0.044 mmol of a ligand (Z) were dissolved in 9 mL solvent at room temperature. The mixture was stirred for 30 min. The solvent was ethyl acetate, isopropanol or methanol. All of the following catalysts [(C1 ) - (C8)] were produced according to the process of Example 1

	at 20℃; for 0.5h;	1 Example 1 : Production of the catalysts In a 25 mL 2-necked round bottomed flask equipped with thermometer and a magnetic stirrer, 0.020 mmol of metal complex (M(Y)X2]2) and 0.044 mmol of a ligand (Z) were dissolved in 9 mL solvent at room temperature. The mixture was stirred for 30 min. The solvent was ethyl acetate, isopropanol or methanol. All of the following catalysts [(C1 ) - (C8)] were produced according to the process of Example 1
	at 20℃; for 0.5h;	1 Example 1 : Production of the catalysts General procedure: In a 25 mL 2-necked round bottomed flask equipped with thermometer and a magnetic stirrer, 0.020 mmol of metal complex (M(Y)X2]2) and 0.044 mmol of a ligand (Z) were dissolved in 9 mL solvent at room temperature. The mixture was stirred for 30 min. The solvent was ethyl acetate, isopropanol or methanol. All of the following catalysts [(C1 ) - (C8)] were produced according to the process of Example 1

Reference： [1]Chen, Yanyan; Dai, Nan; Liu, Libing; Lv, Fengting; Qi, Ruilian; Wang, Shu; Zhao, Hao [Chemistry - A European Journal, 2020]
[2]Soldevila-Barreda, Joan J.; Bruijnincx, Pieter C. A.; Habtemariam, Abraha; Clarkson, Guy J.; Deeth, Robert J.; Sadler, Peter J. [Organometallics, 2012, vol. 31, # 16, p. 5958 - 5967]
[3]Current Patent Assignee: KONINKLIJKE DSM N.V. - WO2015/4088, 2015, A1 Location in patent: Page/Page column 18
[4]Current Patent Assignee: KONINKLIJKE DSM N.V. - WO2015/4117, 2015, A1 Location in patent: Page/Page column 18
[5]Current Patent Assignee: KONINKLIJKE DSM N.V. - WO2015/4116, 2015, A1 Location in patent: Page/Page column 18

29
[ 1415830-54-4 ]
[ 14316-16-6 ]
[ 1415829-69-4 ]

Yield	Reaction Conditions	Operation in experiment
21.9%	With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 100℃; for 16h;	19.2 Step 24-methyl-yV-(2-(2-(naphthalen-2-yl)imidazo[1 ,2-a]pyrazin-8- ylamino)ethyl)benzenesulfonamide (JS209)To a solution of 8TP27 (65.9 mg, 0.310 mmol) in anhydrous DMF (2 ml) was added DIPEA (53.9 μΙ, 0.310 mmol) followed by JS132 (50 mg, 0.155 mmol) and the reaction mixture was stirred at 100 °C for 16 h. Cooling to RT and removal of the solvent was followed by flash chromatography (Toluene; 2:1 Toluene/EtOAc), which yielded the title compound as a white solid (15 mg, 0.0328 mmol, 21 .9%). Mpt: Decomposed before melting; Rf = 0.26 (3:1 EtOAc/Pet Ether); IR (vmax/cm"1, thin film): 3412, 3029, 2924, 2853 (C-H stretch), 1621 , 1538, 1327, 1 158; 1H NMR (600 MHz, CDCI3): δΗ = 2.24 (s, 3H, 29-H), 3.32 (ap.d, J = 4.7 Hz, 2H, 22-H), 3.71 (ap.q, J = 5.6 Hz, 2H, 21 -H), 6.32 (bs, 1 H, 20-H), 6.55 (bs, 1 H, 23-H), 7.10 (d, J = 8.0 Hz, 2H, 23-H), 7.29 (d, J = 4.6 Hz, 1 H, 6-H), 7.45 (d, J = 4.6 Hz, 1 H, 5-H), 7.48-7.52 (m, 2H, 15,16-H), 7.63 (d, J = 8.1 Hz, 2H, 26-H), 7.85-7.86 (m, 2H, 3,14-H), 7.88-7.91 (m, 2H, 12,17-H), 7.94 (ap.d, J = 8.4 Hz, 1 H, 11 -H), 8.37 (s, 1 H, 19-H); 13C NMR (150 MHz, CDCI3): 5C = 21 .6 (C-29), 40.7 (C-21 ), 45.0 (C-22), 1 10.6 (C-5), 1 1 1 .0 (C-3), 124.0 (C-11 ), 124.8 (C-19), 126.4 (C-15), 126.6 (C-16), 127.0 (C-26), 127.9 (C-6,14), 128.4 (C-17), 128.7 (C-12), 129.5 (C-27), 130.4 (C-10), 133.2 (C-9), 133.4 (C-13), 133.7 (C-18), 137.0 (C-25), 143.3 (C-28), 144.9 (C-2), 149.5 (C-8); LRMS m/z (ES+): 458 [M+H]+
21%	With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 100℃; for 16h;	4-Methyl-N-(2-(2-(naphthalen-2-yl)imidazo[1,2-a]pyrazin-8-ylamino)ethyl)benzenesulfonamide(31) 4-Methyl-N-(2-(2-(naphthalen-2-yl)imidazo[1,2-a]pyrazin-8-ylamino)ethyl)benzenesulfonamide(31) To a solution of N-(2-aminoethyl)-4-methylbenzenesulfonamide (65.9 mg, 0.310 mmol) in anhydrous DMF (2 mL) was added DIPEA (53.9µL, 0.310 mmol) followed by 24 (50.0mg, 0.155 mmol) and the reaction mixture was stirred at 100 °C for 16 h. Cooling to RT and removal of the solvent wasfollowed by flash chromatography (applied in toluene; eluted 2:1toluene/EtOAc), which yielded the title compound as a white solid (15 mg, 0.033mmol, 21%). Mpt: 158-160 °C; Rf = 0.26 (3:1 EtOAc/pet.ether); IR (νmax/cm-1, thin film): 3412, 3029, 2924, 2853, 1621, 1538; 1HNMR (600 MHz, CDCl3): δH = 2.24 (s, 3H, 29-H), 3.32 (bd, J = 4.7 Hz, 2H, 22-H),3.70-3.73 (m, 2H, 21-H), 6.32 (bs,1H, 20-H), 6.55 (bs, 1H, 23-H), 7.10 (d, J = 8.1 Hz, 2H, 27-H),7.29 (d, J = 4.6 Hz, 1H, 6-H), 7.45 (d, J = 4.6 Hz, 1H, 5-H),7.48-7.52 (m, 2H, 15,16-H), 7.63 (d,J = 8.1 Hz, 2H, 26-H), 7.85-7.86 (m, 2H, 3,14-H),7.88-7.91 (m, 2H, 12,17-H), 7.94 (d,J = 8.4 Hz, 1H, 11-H), 8.37 (s, 1H, 19-H);1H NMR (600 MHz, (CD3)2SO):δH = 2.30 (s, 3H, 29-H),3.03 (q, J = 6.3 Hz, 2H, 22-H), 3.53 (q, J = 6.3 Hz, 2H, 21-H),7.23-7.24 (m, 3H, 6,27-H), 7.45 (t, J = 5.9 Hz, 1H, 20-H), 7.50-7.56 (m, 2H, 15,16-H),7.63 (d, J = 8.2 Hz, 2H, 26-H), 7.67 (t, J = 5.5 Hz, 1H, 23-H),7.77 (d, J = 4.6 Hz, 1H, 5-H), 7.94 (d, J = 7.9 Hz, 1H, 14-H),7.96 (d, J = 7.9 Hz, 1H, 17-H), 8.00 (d, J = 8.6 Hz, 1H, 12-H),8.11 (dd, J = 8.6, 1.6 Hz, 1H, 11-H), 8.46 (s, 1H, 3-H), 8.52 (s, 1H, 19-H); 13C NMR (150 MHz, CDCl3): δC= 21.6 (C-29), 40.7 (C-21), 45.0 (C-22), 110.6 (C-5),111.0 (C-3), 124.0 (C-11), 124.8 (C-19), 126.4 (C-15),126.6 (C-16), 127.0 (C-26), 127.9 (C-6,14), 128.4 (C-17),128.7 (C-12), 129.5 (C-27), 130.4 (C-10), 133.2 (C-9),133.4 (C-13), 133.7 (C-18), 137.0 (C-25), 143.3 (C-28),144.9 (C-2), 149.5 (C-8);13C NMR (150 MHz, (CD3)2SO):δC = 21.0 (C-29), 40.1 (C-21), 41.6 (C-22), 110.3 (C-5),112.0 (C-3), 123.8 (C-19), 124.1 (C-11), 126.1 (C-15),126.6 (C-16), 126.6 (C-26), 127.7 (C-14), 128.0 (C-17),128.1 (C-6), 128.3 (C-12), 129.4 (C-27), 131.0 (C-10),132.6 (C-13), 132.9 (C-9), 133.2 (C-18), 137.3 (C-25),142.4 (C-28), 143.0 (C-2), 148.4 (C-8); LRMS m/z (ES+): 458 [M+H]+; HRMS m/z(EI+): Found 458.1656 [M+H]+; C25H24N5O2Srequires 458.1651.

Reference： [1]Current Patent Assignee: UNIVERSITY OF LONDON - WO2012/168733, 2012, A1 Location in patent: Page/Page column 102
[2]Sayer, James R.; Walldn, Karin; Pesnot, Thomas; Campbell, Frederick; Gane, Paul J.; Simone, Michela; Koss, Hans; Buelens, Floris; Boyle, Timothy P.; Selwood, David L.; Waksman, Gabriel; Tabor, Alethea B. [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 22, p. 6459 - 6470]

30
[ 124-07-2 ]
[ 14316-16-6 ]
[ 1422144-59-9 ]

Yield	Reaction Conditions	Operation in experiment
94%	With ethanaminium,N-(difluoro-λ⁴-sulfanylidene)-N-ethyl-,tetrafluoroborate In tetrahydrofuran at 0 - 20℃; for 4h; Inert atmosphere; Cooling with ice;

Reference： [1]Orliac, Aurélie; Gomez Pardo, Domingo; Bombrun, Agnès; Cossy, Janine [Organic Letters, 2013, vol. 15, # 4, p. 902 - 905]

31
[ 24424-99-5 ]
[ 14316-16-6 ]
[ 134360-52-4 ]

Yield	Reaction Conditions	Operation in experiment
79%	With triethylamine In dichloromethane at 0 - 20℃; for 1.5h;