Name: 14068-53-2|5-Ethyl-1,3,4-thiadiazol-2-amine|97%
Brand: Ambeed
SKU: A386660
Rating: 93 (26 reviews)

1
[ 14068-53-2 ]
[ 121-60-8 ]
[ 1037-51-0 ]

Yield	Reaction Conditions	Operation in experiment
70%	With pyridine at 95℃; for 1h;	N-(4-(N-(5-Ethyl-1,3,4-thiadizol-2-yl)sulfamoyl)phenyl)acetamide (10). General procedure: Compound 9 is commercially available. Alternatively, 2-amino-5-methyl-1,3,4-thiadiazole (250 mg, 2.19 mmol) was suspended in pyridine (0.5 mL). N-Acetylsulfanilyl chloride (410 mg, 1.75 mmol) was added slowly at 0 °C. The reaction mixture was then heated to 95 °C and was stirred for 1 h. The reaction mixture was then added to aqueous 3N HCl and the mixture extracted with EtOAc. The organic extracts were washed with water (3 ' 20 mL), brine (3 ' 20 mL), dried over anhydrous Na2SO4, filtered, and volatiles evaporated in vacuo. The residue was crystallized from MeOH to give 9 (491 mg, 1.6 mmol, 97%),
70%	With pyridine at 0 - 95℃;	1 -Amino-5-ethyl-l,3,4-thiadiazole (250 mg, 1.93 mmol) was suspended in pyridine (0.5 mL). /V-Acetylsulfanilyl chloride (361 mg, 1.54 mmol) was added slowly at 0 0C. The reaction mixture was then heated to 95 0C and was stirred for 1 h. The reaction mixture was then added to aqueous 3N HCl and the mixture extracted with ethyl acetate. The organic extracts were washed with water (3 x 20 mL), brine (3 x 20 mL), dried over anhydrous Na2SO4, filtered, and volatiles evaporated. The residue was crystallized from MeOH to give the product (350 mg, 1.07 mmol, 70%) as a solid, mp 197-198 0C; 1H NMR (500 MHz, DMSO) δ 1.28 (3, t, J= 7.0 Hz), 2.07 (3, s), 2.82 (2, q, J= 7.0 Hz), 7.72 (4, s), 10.32 (1, s), 13.91 (1, s); 13C NMR (125 MHz, DMSO) δ 12.2, 23.7, 24.1, 48.6, 118.5, 126.9, 135.6, 142.7, 159.8, 167.3, 168.9; MS (LCQ, ESI+) Calculated for C12Hi5N4O3S2 327.1, found 327.1 (M+H)+; HRMS (FAB+, m/z) Calculated for Ci2Hi5N4O3S2 327.0586, found 327.0585 (M+H)+.
	With pyridine

Reference： [1]Ahad, Ali Md.; Zuohe, Song; Du-Cuny, Lei; Moses, Sylvestor A.; Zhou, Li Li; Zhang, Shuxing; Powis, Garth; Meuillet, Emmanuelle J.; Mash, Eugene A. [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 6, p. 2046 - 2054]
[2]Current Patent Assignee: THE UNIVERSITY OF TEXAS SYSTEM; ARIZONA BOARD OF REGENTS - WO2009/129267, 2009, A2 Location in patent: Page/Page column 90-91
[3]Wojahn; Wuckel [Archiv der Pharmazie, 1951, vol. 284, p. 53,57]

2
[ 14068-53-2 ]
[ 71859-81-9 ]

Yield	Reaction Conditions	Operation in experiment
79%	With hydrogenchloride; copper; sodium nitrite In water at -5 - 55℃;
35%	With hydrogenchloride; copper; acetic acid; sodium nitrite In water at 15 - 20℃;	1 To a mixture of 5-(l-ethyl-lH-pyrazol-4-yl)-[l,3,4]thiadiazol-2-ylamine (5.0 g, 0.04mol), Cu (0.39 g), in 37% aq. HCl (25mL) and HOAc (75mL) was dropwise added aq. NaNO2 (2.3g, 0.039 mol) in H2O (1OmL) at 150C. Then the mixture was stirred at room temperature overnight, poured into water and extracted with CHCI3, the aqueous layer was concentrated and basified with 50% NaOH and extracted with CHCI3, combined the organic layer and dried with Na2Sθ4 and concentrated in vacuum to give crude 2-chloro-5-(l-ethyl-lH-pyrazol- 4-yl)-[l,3,4]thiadiazole. Then the crude product was purified with chromatography to give 2-chloro-5-(l-ethyl- lH-pyrazol-4-yl)-[l,3,4]thiadiazole (2.0 g, 35 %) as a white solid. ES-MS m/z: 149(M+H+).
	With hydrogenchloride; sodium nitrite anschliessend mit Kupfer behandeln;

With hydrogenchloride; copper; sodium nitrite

Reference： [1]Location in patent: experimental part Cressier, Damien; Prouillac, Caroline; Hernandez, Pierre; Amourette, Christine; Diserbo, Michel; Lion, Claude; Rima, Ghassoub [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 14, p. 5275 - 5284]
[2]Current Patent Assignee: ELI LILLY & CO - WO2008/144767, 2008, A1 Location in patent: Page/Page column 119
[3]Kanaoka [Pharmaceutical Bulletin, 1957, vol. 5, p. 385,387, 388]
[4]Russo; Santagati; Santagati [Farmaco, Edizione Scientifica, 1979, vol. 34, # 8, p. 688 - 697]

3
[ 79-03-8 ]
[ 79-19-6 ]
[ 14068-53-2 ]

Yield	Reaction Conditions	Operation in experiment
83%	at 40℃; for 4h; Neat (no solvent);	11 A mixture of 25 g (0.27 mol) of thiosemicarbazide and 46.6 ml propanoyle chloride (0.54 mol, 2 eq) is agitated at 40° C. for 4 h. The propanoyle chloride excess is then evaporated under a vacuum and the residue is triturated in ether. A solid product is obtained. It contains the expected thiadiazole and an impurity that is eliminated by precipitation in ethanol. White solid, 33.6 g (Yield: 83%) Kromasil C18 HPLC Tr 6.32 min in 30% CH3CN.

Reference： [1]Current Patent Assignee: PHARMALEADS SAS - US2009/12153, 2009, A1 Location in patent: Page/Page column 12
[2]Current Patent Assignee: PFIZER INC - US2497825, 1946, A Takatori et al. [Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1959, vol. 79, p. 913,915, 916][Chem.Abstr., 1960, p. 514]
[3]Current Patent Assignee: PFIZER INC - US2422050, 1945, A

4
[ 14068-53-2 ]
[ 67475-55-2 ]
[ 67475-18-7 ]

Reference： [1]Pharmazie,1978,vol. 33,p. 254 - 256

5
[ 14068-53-2 ]
[ 67475-56-3 ]
[ 67475-19-8 ]

Reference： [1]Pharmazie,1978,vol. 33,p. 254 - 256

6
[ 14068-53-2 ]
[ 407-25-0 ]
[ 22926-50-7 ]

Yield	Reaction Conditions	Operation in experiment
88%	In toluene
85%	With N-ethyl-N,N-diisopropylamine In toluene for 1h; Ambient temperature;

Reference： [1]Hirata, Terukage; Nomiyama, Jun; Sakae, Nobuya; Nishimura, Kouji; Yokomoto, Masaharu; Inoue, Satoshi; Tamura, Koichi; Okuhira, Masayasu; Amano, Hirotaka; Nagao, Yoshimitsu [Bioorganic and Medicinal Chemistry Letters, 1996, vol. 6, # 13, p. 1469 - 1474]
[2]Nagao, Yoshimitsu; Hirata, Terukage; Goto, Satoru; Sano, Shigeki; Kakehi, Akikazu; Iizuka, Kinji; Shiro, Motoo [Journal of the American Chemical Society, 1998, vol. 120, # 13, p. 3104 - 3110]
[3]Gagiu; Daicoviciu; Binder; Gyoerfi [Pharmazie, 1969, vol. 24, # 2, p. 98 - 99]

8
[ 14068-53-2 ]
[ 58755-91-2 ]
[ 139477-32-0 ]

Reference： [1]Pharmazie,1991,vol. 46,p. 705 - 707

9
[ 14068-53-2 ]
[ 79-04-9 ]
[ 21521-90-4 ]

Yield	Reaction Conditions	Operation in experiment
92%	In benzene for 3h; Heating;
80%	In 1,4-dioxane for 1h; Heating;
	In benzene Heating;

Reference： [1]Shakya; Patnaik; Mishra [European Journal of Medicinal Chemistry, 1992, vol. 27, # 1, p. 67 - 71]
[2]Mishra; Shakya; Agrawal; Patnaik [Journal of the Indian Chemical Society, 1990, vol. 67, # 6, p. 520 - 521]
[3]Gupta; Misra [Journal of Pharmaceutical Sciences, 1980, vol. 69, # 11, p. 1313 - 1317]

10
[ 14068-53-2 ]
[ 98-74-8 ]
[ 76170-72-4 ]

Yield	Reaction Conditions	Operation in experiment
95%	With pyridine at 20℃; for 3h;
	In chlorobenzene at 115 - 120℃; for 2h; Yield given;

Reference： [1]Ganesh, Thota; Jiang, Jianxiong; Shashidharamurthy, Rangaiah; Dingledine, Ray [ACS Medicinal Chemistry Letters, 2013, vol. 4, # 7, p. 616 - 621]
[2]Luk'yanov, A. V.; Onoprienko, V. S.; Borodina, K. S.; Zasosov, V. A.; Van'kovich, E. V.; et al. [Pharmaceutical Chemistry Journal, 1980, vol. 14, # 9, p. 640 - 644][Khimiko-Farmatsevticheskii Zhurnal, 1980, vol. 14, # 9, p. 87 - 91]

11
[ 802294-64-0 ]
[ 79-19-6 ]
[ 14068-53-2 ]

Yield	Reaction Conditions	Operation in experiment
92.6%	With silica gel; trichlorophosphate at 20℃; for 0.166667h;	2 1) was added 0.05mol thiosemicarbazide To a dry mortar, 0.055 mol propionic acid, and 0.055 mol of phosphorus oxychloride 0.25mol silica gel, triturated at room temperature 10min, at which time TLC monitoring showed starting material thiosemicarbazide point disappears, indicating material complete reaction, then allowed to stand 30min, to obtain a crude product; TLC developing solvent wherein the volume ratio of 1: 3 mixture of ethyl acetate and petroleum ether; document.write(""); 2) The crude product was transferred to a beaker, was added to the crude product concentration of 5% sodium carbonate solution, pH of the resulting mixture to a value of 8, and then the mixture is filtered off with suction, the resulting cake with a solvent DMF after dissolution continued suction filtration, silica gel was removed, and then the resulting filtrate was concentrated under reduced pressure, the solvent was removed, and then concentrated under reduced pressure to give the product washed with water, filtered off with suction, i.e. 2-amino-5-ethyl-1,3, 4- thiadiazole, yield 92.6%.
90.3%	With hydrogenchloride In water for 5h; Reflux;
84%	With poly(ethylene glycol) supported dichlorophosphate at 120℃; for 0.0833333h; microwave irradiation;

80%	With sulfuric acid
78%	With sulfuric acid for 0.133333h; Microwave irradiation;
70%	With sulfuric acid for 6h; Heating;
64.5%	With methanesulfonic acid; phosphorus pentoxide at 70℃; for 10h;
58%	With sulfuric acid
51%	With sulfuric acid for 2h; Heating;
50%	With sulfuric acid for 3h; Heating;
	With trichlorophosphate Irradiation;
	With trichlorophosphate Microwave irradiation;
	Reflux;
	With hydrogen bromide at 105℃; for 4.7h;	1.1 the solid thiosemicarbazide,Formic acid and hydrobromic acid,Open the oil bath heating and stirring,The solid thiosemicarbazide and formic acid mass ratio of 6: 1,Formic acid mass fraction of 90%, hydrobromic acidMass fraction of 50%; heating to 105 incubated for 4.5 hours, the reaction was completed and cooled to room temperature;Ice water bath with 40% sodium hydroxide solution to adjust the pH to 8 ~ 9;The reaction solution precipitated solid, ice-water bathUnder 30 minutes to fully precipitate; vacuum filtration, filter cake was collected and dried to give the crude product;The crude product is recrystallized from 30% aqueous ethanol and dried to obtain 2-amino-1,3,4-thiadiazole.
	With trichlorophosphate at 75℃; for 1h;	4.1.2. General procedure for the preparation 5-substituted-1,3,4-thiadiazol-2-amines 4a-4f General procedure: To a round-bottom flask were added thiosemicarbazide (10 mmol,1.0 eq.), carboxylic acid (11 mmol, 1.1 eq.) and POCl3 (5 mL). The resulting mixture was heated to 75 °C and stirred for 1 h. The reaction mixture was then cooled to room temperature, to which tepid water(10 mL) was slowly added, and it was further heated to reflux and stirred for 1 h. After cooling, the reaction mixture was neutralized with 50% NaOH and the precipitated solid was collected by filtration and washed with water. The crude product was then recrystallized from ethanol. Yield 70-80%.

Reference： [1]Current Patent Assignee: SHAANXI UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN103880776, 2016, B Location in patent: Paragraph 0028-0030
[2]Yuting, Liu; Gangtao, Liang; Dawei, Yin [Journal of the Chemical Society of Pakistan, 2015, vol. 37, # 1, p. 115 - 121]
[3]Li, Zheng; Yu, Jin-Lan; Yang, Jing-Ya; Shi, Sheng-Yi; Wang, Xi-Cun [Journal of Chemical Research, 2005, # 5, p. 341 - 343]
[4]Mishra; Shakya; Agrawal; Patnaik [Journal of the Indian Chemical Society, 1990, vol. 67, # 6, p. 520 - 521]
[5]Jha, Anjali; Murthy; Sanyal; Durga [Medicinal Chemistry Research, 2012, vol. 21, # 9, p. 2548 - 2556]
[6]Pandey; Tusi, Sarah; Tusi, Zehra; Raghubir; Dixit; Joshi; Bajpai [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 1, p. 180 - 183]
[7]Tsuji, Tadakazu; Takenaka, Keiko [Bulletin of the Chemical Society of Japan, 1982, vol. 55, # 2, p. 637 - 638]
[8]Pandey; Tusi; Tandon; Joshi; Bajpai [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2003, vol. 42, # 10, p. 2583 - 2588]
[9]Pandey; Negi; Joshi; Bajpai [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2003, vol. 42, # 1, p. 206 - 210]
[10]Location in patent: experimental part Samel, Amarish B.; Pai, Nandini R. [Journal of the Chinese Chemical Society, 2010, vol. 57, # 6, p. 1327 - 1330]
[11]Xiaodong, Yang [Heterocyclic Communications, 2007, vol. 13, # 6, p. 387 - 392]
[12]Location in patent: scheme or table Liu, Xing-Hai; Shi, Yan-Xia; Ma, Yi; Zhang, Chuan-Yu; Dong, Wei-Li; Pan, Li; Wang, Bao-Lei; Li, Bao-Ju; Li, Zheng-Ming [European Journal of Medicinal Chemistry, 2009, vol. 44, # 7, p. 2782 - 2786]
[13]Meng, Wen-Fei; Yang, Mei-Pan; Li, Bo; Cheng, Zhao; Yang, Bing-Qin [Tetrahedron, 2014, vol. 70, # 45, p. 8577 - 8581]
[14]Current Patent Assignee: ZHANGJIAGANG MAOAN TRADE - CN107501343, 2017, A Location in patent: Paragraph 0027; 0037
[15]Peng, Kewen; Li, Yu; Bai, Ying; Jiang, Teng; Sun, Huiyong; Zhu, Qihua; Xu, Yungen [Bioorganic and Medicinal Chemistry, 2020, vol. 28, # 1]

12
[ 14068-53-2 ]
[ 550-24-3 ]
[ 160562-17-4 ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1994,vol. 33,p. 1189 - 1190

13
[ 14068-53-2 ]
[ 135-19-3 ]
[ 523999-52-2 ]

Yield	Reaction Conditions	Operation in experiment
58%	Stage #1: 2-amino-5-ethyl-1,3,4-thiadiazole With hydrogenchloride; sodium nitrite at 0℃; for 1h; Stage #2: β-naphthol With sodium hydroxide at 0 - 5℃; Stage #3: With hydrogenchloride In water at 20℃; for 0.5h;

Reference： [1]Pandey; Negi; Joshi; Bajpai [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2003, vol. 42, # 1, p. 206 - 210]

14
[ 14068-53-2 ]
[ 105-56-6 ]
[ 544431-10-9 ]

Yield	Reaction Conditions	Operation in experiment
55%	With sodium methylate In methanol for 8h; Heating;
55%	Stage #1: 2-amino-5-ethyl-1,3,4-thiadiazole; ethyl 2-cyanoacetate With sodium methylate In methanol for 8h; Heating / reflux; Stage #2: With acetic acid In methanol; water at 0℃;	1.A To a N2 purged 250 mL flask, attached with cooling condenser and stir bar, was added 5-ethyl-2-amino- [1, 3, 4]-thiadiazole (6.05 g, 46.8 mmol), anhydrous MeOH (110 mL), ethyl cyanoacetate (5.0 mL, 47.0 mmol), and a 25 wt% solution of sodium methoxide in MeOH (12.8 mL, 56.3 mmol). The mixture was stirred at reflux for 8 h. The reaction solution was cooled to ambient temperature and poured into 600 mL of ice water. The pH was lowered to pH = 5 by the dropwise addition of acetic acid. The resulting white precipitates were filtered under reduced pressure. The crude product was dissolved in hot MeOH (450 mL), and a fine white precipitate was allowed to form as the mixture was cooled to ambient ambient temperature. The product was isolated by filtration under reduced pressure to provide 4.90 g (55 % yield) of title compound.'H NMR (DMSOd6) 6 12.8 (1H, br s), 4.07 (2H, s), 3.00 (2H, q, J = 7.5 Hz), 1.30 (3H, t, J = 7. 5 Hz) ; IR (KBr) vmax 3195,2916, 2749,2260, 1698,1582 cm-' ; MS (ESI) : 197 (MH+).

Reference： [1]Busch, Brett B.; Stevens Jr., William C.; Martin, Richard; Ordentlich, Peter; Zhou, Sihong; Sapp, Douglas W.; Horlick, Robert A.; Mohan, Raju [Journal of Medicinal Chemistry, 2004, vol. 47, # 23, p. 5593 - 5596]
[2]Current Patent Assignee: EXELIXIS INC - WO2005/72731, 2005, A1 Location in patent: Page/Page column 46

15
[ 14068-53-2 ]
[ 99-81-0 ]
2-ethyl-6-(4-nitrophenyl)imidazo[2,1-b][1,3,4]thiadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	for 8h; Reflux;	General procedure for 2-R-6-arylimidazo[2,1-b][1,3,4]thiadiazoles synthesis (2) General procedure: Mixture of 2-amino-5-R-1,3,4-thiadiazole (1.0 eq.) and 2-bromoacetophenone (1.0 eq.) in ethanol was heated under reflux for 8h. The reaction mixture was cooled and water solution of sodium carbonate was added (pH=9.0). The formed precipitate was filtered off and washed, dried and recrystallized from appropriate solvent [62].
62%	In ethanol for 8h; Heating;

Reference： [1]Kryshchyshyn, Anna; Kaminskyy, Danylo; Karpenko, Oleksandr; Gzella, Andrzej; Grelier, Philippe; Lesyk, Roman [European Journal of Medicinal Chemistry, 2019, vol. 174, p. 292 - 308]
[2]Begum, Noor Shahina; Vasundhara; Girija; Kolavi; Hegde; Khazi [Journal of Chemical Research, 2006, # 5, p. 286 - 288]

16
[ 337962-91-1 ]
[ 14068-53-2 ]
[ 388630-83-9 ]

Yield	Reaction Conditions	Operation in experiment
92%	With 4-methyl-morpholine; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide at 100℃;
92%	With 4-methyl-morpholine; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In N,N-dimethyl-formamide at 100℃; for 12h;

Reference： [1]Pryde, David C.; Maw, Graham N.; Planken, Simon; Platts, Michelle Y.; Sanderson, Vivienne; Corless, Martin; Stobie, Alan; Barber, Christopher G.; Russell, Rachel; Foster, Laura; Barker, Laura; Wayman, Christopher; Van Der Graaf, Piet; Stacey, Peter; Morren, Debbie; Kohl, Christopher; Beaumont, Kevin; Coggon, Sara; Tute, Michael [Journal of Medicinal Chemistry, 2006, vol. 49, # 14, p. 4409 - 4424]
[2]Pryde, David C.; Cook, Andrew S.; Burring, Denise J.; Jones, Lyn H.; Foll, Stephanie; Platts, Michelle Y.; Sanderson, Vivienne; Corless, Martin; Stobie, Alan; Middleton, Donald S.; Foster, Laura; Barker, Laura; Van Der Graaf, Piet; Stacey, Peter; Kohl, Christopher; Coggon, Sara; Beaumont, Kevin [Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 1, p. 142 - 159]

17
[ 906069-62-3 ]
[ 14068-53-2 ]
[ 906069-94-1 ]

Yield	Reaction Conditions	Operation in experiment
65%	With 4-methyl-morpholine; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In N,N-dimethyl-formamide at 100℃; for 12h;

Reference： [1]Pryde, David C.; Maw, Graham N.; Planken, Simon; Platts, Michelle Y.; Sanderson, Vivienne; Corless, Martin; Stobie, Alan; Barber, Christopher G.; Russell, Rachel; Foster, Laura; Barker, Laura; Wayman, Christopher; Van Der Graaf, Piet; Stacey, Peter; Morren, Debbie; Kohl, Christopher; Beaumont, Kevin; Coggon, Sara; Tute, Michael [Journal of Medicinal Chemistry, 2006, vol. 49, # 14, p. 4409 - 4424]

18
[ 906070-10-8 ]
[ 14068-53-2 ]
[ 906069-95-2 ]

Yield	Reaction Conditions	Operation in experiment
63%	With 4-methyl-morpholine; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide at 100℃;

Reference： [1]Pryde, David C.; Maw, Graham N.; Planken, Simon; Platts, Michelle Y.; Sanderson, Vivienne; Corless, Martin; Stobie, Alan; Barber, Christopher G.; Russell, Rachel; Foster, Laura; Barker, Laura; Wayman, Christopher; Van Der Graaf, Piet; Stacey, Peter; Morren, Debbie; Kohl, Christopher; Beaumont, Kevin; Coggon, Sara; Tute, Michael [Journal of Medicinal Chemistry, 2006, vol. 49, # 14, p. 4409 - 4424]

19
[ 14068-53-2 ]
[ 437-81-0 ]
[ 68-11-1 ]
C₁₃H₁₁F₂N₃OS₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	In toluene Heating;
44%	With toluene-4-sulfonic acid In toluene at 120℃; Molecular sieve;

Reference： [1]Rawal, Ravindra K.; Tripathi, Rajkamal; Katti; Pannecouque, Christophe; De Clercq, Erik [Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 4, p. 1725 - 1731]
[2]Rawal, Ravindra K.; Katti; Kaushik-Basu, Neerja; Arora, Payal; Pan, Zhenhua [Bioorganic and Medicinal Chemistry Letters, 2008, vol. 18, # 23, p. 6110 - 6114]

20
[ 14068-53-2 ]
[ 1885-14-9 ]
[ 606129-66-2 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In dichloromethane at -70 - 20℃; for 3h;	A solution of S-ETHYL- [1, 3,4] thiadiazol-2-ylamine (2. 5g, 19.4mmol) and pyridine (1.72 ml, 21.3mmol) in dichloromethane (70 ml) is cooled to-70°C and treated with a solution of phenylchloroformate (2. 45 ml, 19.6 mmol) in dichloromethane (10 ml) dropwise. The reaction mixture is allowed to warm to ambient temperature and stirred for 3 hours during which a precipitate forms. The precipitate is collected by filtration, and dried under vacuum to afford (S-ETHYL- [1, 3,4] thiadiazol-2-yl)-carbamic acid phenyl ester as white solid. [M+H] 250. 15

Reference： [1]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2005/26113, 2005, A1 Location in patent: Page 34

21
[ 14068-53-2 ]
[ 19241-36-2 ]
[ 221089-37-8 ]

Yield	Reaction Conditions	Operation in experiment
34%	With hydrogenchloride	14 1-(5-Chloro-2-methyl-phenyl)-3-(5-ethyl-[1,3,4]thiadiazol-2-yl)-thiourea EXAMPLE 14 1-(5-Chloro-2-methyl-phenyl)-3-(5-ethyl-[1,3,4]thiadiazol-2-yl)-thiourea Prepared using Method D from 4.5 g (24.5 mmol) of 5-chloro-2-methyl-phenyl isothiocyanate and 3.16 g (24.5 mmol) of 5-amino-2-ethyl-[1,3,4]thiadiazole to give 3.0 g of residual solids. Pure title compound was obtained by trituration of the crude solid with 1N HCl. The solids were collected, washed with H2O, EtOAc and dried under high vacuum to give 2.55 g of the title compound as a white solid (34% yield, m.p. sinters 170° C., melts 231-233° C. with decomposition). NMR (DMSO-d6, 400 MHz): 1.24 (t, 3H, CH2CH3), 2.152 (s, 3H, ArCH3), 2.84 (q, 2H, CH2CH3), 7.20 (dd, 1H, ArH), 7.26 (d, 1H, ArH), 7.34 (s, 1H, ArH), 10.04 (s, 1H, NH), 13.5 (broad, 1H, NH). MS [EI, m/z]: 312 [M]+, 279, 129 [b.p.]; Anal. Calc'd. for C12H13ClN4S2: C, 46.07; H, 4.19; N, 17.19 Found: C, 46.21; H, 4.13; N, 17.99.

Reference： [1]Current Patent Assignee: PFIZER INC - US6455566, 2002, B1

22
[ 14068-53-2 ]
[ 22926-50-7 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; trifluoroacetic anhydride In di-isopropyl ether; water; ethyl acetate; toluene	R.2 Referential Example 2 Referential Example 2 Synthesis of 5-ethyl-2-trifluoroacetylamino-1,3,4-thiadiazole To a suspension of 2-amino-5-ethyl-1,3,4-thiadiazole (1.29 g) in toluene (24 ml) was added triethylamine (3.1 ml) at room temperature, followed by the dropwise addition of trifluoroacetic anhydride (4.62 g) on ice. The resulting mixture was stirred at room temperature for one hour. Water and ethyl acetate were added to the reaction mixture to cause separation and the organic layer was dried over anhydrous magnesium sulfate, followed by removal through distillation. The crystals so obtained were dispersed in diisopropyl ether, collected by filtration and then dried, whereby 1.21 g of the title compound was obtained. 1 H-NMR (CDCl3): 1.44(3H,t,J=8 Hz), 3.09(2H,q,J=8 Hz)
237.5g (68%)	With triethylamine; trifluoroacetic anhydride In water; ethyl acetate; toluene	S.1.1 Synthesis Example 1 (1) Synthesis of 2-trifluoroacetamido-5-ethyl-1,3,4-thiadiazole To a suspension of 200 g of 2-amino-5-ethyl-1,3,4-thiadiazole in 3 L of toluene was added 260 mL of triethylamine at room temperature followed by the addition of 265 mL of trifluoroacetic anhydride under ice cooling. The mixture was stirred for one hour at room temperature. To the reaction mixture was added water and precipitated crystals were collected by filtration. Ethyl acetate was added to the filtrate. The organic layer was separated and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo to afford 237.5g (68%) of the title compound.
	With triethylamine; trifluoroacetic anhydride In water; ethyl acetate; toluene	6.1 (1) (1) Production of 2-trifluoroacetamido-5-ethyl-1,3,4-thiadiazole To a suspension of 200 g of 2-amino-5-ethyl-1,3,4-thiadiazole in 3 L of toluene was added to 260 mL of triethylamine at room temperature; under cooling with ice, to the mixture was added dropwise 265 mL of trifluoroacetic anhydride, and the mixture was stirred at room temperature for 1 h. Water was added to the reaction mixture, and the crystalline precipitate was recovered by filtration. Further, ethyl acetate was added to the filtrate and the organic layer was separated off and dried with anhydrous magnesium sulfate; thereafter, the solvent was distilled off under vacuum to yield the title compound in an amount of 237.5 g (68%).

With triethylamine; trifluoroacetic anhydride In water; ethyl acetate; toluene

R.2 Synthesis of 2-trifluoroacetamido-5-ethyl-1,3,4-thiadiazole Referential Example 2 Synthesis of 2-trifluoroacetamido-5-ethyl-1,3,4-thiadiazole To a suspension of 200 g of 2-amino-5-ethyl-1,3,4-thiadiazole in 3 liters of toluene, was added 260 ml of triethylamine at room temperature. To the mixture was added dropwise 265 ml of trifluoroacetic anhydride on ice, followed by stirring at room temperature for one hour. Water was added to the reaction mixture, and the crystals so precipitated were collected by filtration. Ethyl acetate was added to the filtrate. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure, whereby 237.5 g of the title compound was obtained. 1 H-NMR (CDCl3): 1.44 (3H, t, J=8 Hz), 3.09 (2H, q, J=8 Hz)

Reference： [1]Current Patent Assignee: WAKUNAGA PHARMACEUTICAL CO., LTD. - US5965738, 1999, A
[2]Current Patent Assignee: VAKUNAGA SEJJAKU KABUSIKI KAJS; WAKUNAGA PHARMACEUTICAL CO., LTD. - EP744402, 1996, A1
[3]Current Patent Assignee: WAKUNAGA PHARMACEUTICAL CO., LTD.; CHUGOKU KAYAKU CO., LTD. - EP838458, 1998, A1
[4]Current Patent Assignee: WAKUNAGA PHARMACEUTICAL CO., LTD. - US5912353, 1999, A

23
[ 14068-53-2 ]
[ 24424-99-5 ]
[ 167007-65-0 ]

Yield	Reaction Conditions	Operation in experiment
	In water; N,N-dimethyl-formamide	R.5 2-t-Butyloxycarbonylamino-5-ethyl-1,3,4-thiadiazole Reference Example 5 2-t-Butyloxycarbonylamino-5-ethyl-1,3,4-thiadiazole 2-Amino-5-ethyl-1,3,4-thiadiazole (3.88 g) and di-t-butyldicarbonate (7.19 g) were added to N,N-dimethylformamide (120 ml). To the solution was added catalytic amount of 4-dimethylaminopyridine followed by stirring at 60° C. for 12 hours. After cooling, water (200 ml) was added with vigorously stirring. The mixture was further stirred for 30minutes. The precipitated crystals were filtrated and dried. The title compound was obtained as colorless crystals (12 g).

Reference： [1]Current Patent Assignee: WAKUNAGA PHARMACEUTICAL CO., LTD. - US5654322, 1997, A

24
ammonium thiocyanate [ No CAS ]
[ 14068-53-2 ]
[ 67305-24-2 ]
[ 1023696-85-6 ]

Yield	Reaction Conditions	Operation in experiment
85.8%	Stage #1: ammonium thiocyanate; 5-methylisoxazole-4-carbonyl chloride In dichloromethane at 20℃; for 0.333333h; Irradiation; Stage #2: 2-amino-5-ethyl-1,3,4-thiadiazole In dichloromethane for 0.5h; Irradiation; Further stages.;

Reference： [1]Xiaodong, Yang [Heterocyclic Communications, 2007, vol. 13, # 6, p. 387 - 392]

25
[ 14068-53-2 ]
[ 4023-34-1 ]
[ 354542-00-0 ]

Yield	Reaction Conditions	Operation in experiment
81.2%	With triethylamine In tetrahydrofuran at 20℃;

Reference： [1]Location in patent: experimental part Liu, Xing-Hai; Shi, Yan-Xia; Ma, Yi; Zhang, Chuan-Yu; Dong, Wei-Li; Pan, Li; Wang, Bao-Lei; Li, Bao-Ju; Li, Zheng-Ming [European Journal of Medicinal Chemistry, 2009, vol. 44, # 7, p. 2782 - 2786]

26
[ 14068-53-2 ]
[ 79-03-8 ]
[ 25958-42-3 ]

Yield	Reaction Conditions	Operation in experiment
96%	With triethylamine In tetrahydrofuran at 20℃;

Reference： [1]Location in patent: experimental part Cressier, Damien; Prouillac, Caroline; Hernandez, Pierre; Amourette, Christine; Diserbo, Michel; Lion, Claude; Rima, Ghassoub [Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 14, p. 5275 - 5284]

27
[ 14068-53-2 ]
[ 52499-14-6 ]
[ 1191951-59-3 ]

Yield	Reaction Conditions	Operation in experiment
59%	With pyridine at 95℃; for 1h;	2.1.10. 4-Dodecyl-N-(5-ethyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide (34) General procedure: A suspension of 2-amino-5-methyl-1,3,4-thiadiazole (150 mg, 1.3 mmol) in pyridine (0.5 mL) was stirred and cooled in an ice bath while p-dodecylbenzenesulfonyl chloride (300 mg, 0.87 mmol) was added slowly. The reaction mixture was allowed to attain rt, then heated in an oil bath at 95 °C for 1 h. The reaction mixture was then cooled, added to aqueous 10% HCl (5 mL), and the resulting mixture extracted with EtOAc (3 × 10 mL). The organic extracts were washed with water, brine, dried over anhydrous Na2SO4, filtered, and volatiles evaporated in vacuo to yield a solid mass. Chromatography on silica gel (70-230 mesh) eluted with CH2Cl2/MeOH 49:1 gave the product 33 (310 mg, 0.73 mmol, 84%),
59%	With pyridine at 0 - 95℃;	1 - Amino-5-ethyl-l,3,4-thiadiazole (169 mg, 1.3 mmol) was suspended in pyridine (0.5 mL). p- Dodecylbenzenesulfonyl chloride (300 mg, 0.87 mmol) was added slowly at 0 0C. The reaction mixture was then heated to 95 0C and was stirred at this temperature for 1 h. The reaction mixture was then added to aqueous 10% HCl (5 mL) and the resulting mixture extracted with ethyl acetate (3 x 10 mL). The organic extracts were washed with water, brine, dried over anhydrous Na2SO4, filtered, and volatiles evaporated to yield a solid mass. Chromatography on silica gel (70-230 mesh) eluted with 2% MeOH in CH2Cl2 gave the product (225 mg, 0.51 mmol, 59%). Recrystallization from hexanes:ethyl acetate (3:7) gave an analytical sample, mp 93-94 0C; 1H NMR (500 MHz, CDCl3) δ 0.88 (3, t, J = 6.5 Hz), 1.20-1.36 (18, m), 1.33 (3, t, J= 7.5 Hz), 1.54-1.63 (2, m), 2.63 (2, t, J= 7.5 Hz), 2.84 (2, q, J = 7.5 Hz), 7.25 (2, d, J = 8.5 Hz), 7.83 (2, d, J = 8.5 Hz), 12.30 (1, br s); 13C NMR (125 MHz, CDCl3) δ 12.6, 14.1, 22.7, 24.4, 29.2, 29.3, 29.4, 29.5, 29.6, 31.1, 31.9, 35.9, 126.5, 128.8, 138.4, 148.2, 160.1 168.2; MS (ESI+, m/z) Calcd for C22H36N3O2S2 438.2249, found 438.30 (M+H)+; HRMS (ESI+, m/z) Calcd for C22H36N3O2S2 438.2249, found 438.2247 (M + H)+.

Reference： [1]Location in patent: experimental part Ahad, Ali Md.; Zuohe, Song; Du-Cuny, Lei; Moses, Sylvestor A.; Zhou, Li Li; Zhang, Shuxing; Powis, Garth; Meuillet, Emmanuelle J.; Mash, Eugene A. [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 6, p. 2046 - 2054]
[2]Current Patent Assignee: THE UNIVERSITY OF TEXAS SYSTEM; ARIZONA BOARD OF REGENTS - WO2009/129267, 2009, A2 Location in patent: Page/Page column 86

28
[ 14068-53-2 ]
[ 935481-12-2 ]
C₂₄H₃₆N₄O₃S₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h;	13 Disulfide 5, 6 or 7 (0.54 mmol) is dissolved in 5 ml of CH2Cl2 and the aminothiadiazole of example 11 (1.2 eq), TBTU (O-benzotriazol-1-yl-N,N,N',N'-tetramethyluroniumtetrafluoroborate) (3 eq) and DIEA (diisopropylethylamine) (3 eq) are successively added. The mixture is agitated for 30 minutes at room temperature (approximately 20° C.). The solvent is evaporated under a vacuum and the residue taken up in ethyl acetate. The organic phase is washed with citric acid, water, saturated NaCl and dried on Na2SO4. After vacuum filtration and evaporation, a white solid is obtained.

Reference： [1]Current Patent Assignee: PHARMALEADS SAS - US2009/12153, 2009, A1 Location in patent: Page/Page column 13

29
[ 14068-53-2 ]
[ 13036-50-5 ]
[ 1236002-83-7 ]

Reference： [1]Tetrahedron Letters,2010,vol. 51,p. 3259 - 3262

30
[ 14068-53-2 ]
[ 75634-04-7 ]
[ 1236002-84-8 ]

Yield	Reaction Conditions	Operation in experiment
48%	With potassium phosphate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 160℃; for 6h; Inert atmosphere;

Reference： [1]Bliss, Brian I.; Ahmed, Feryan; Iyer, Subashree; Lin, Weimin; Walker, Joel; Zhao, He [Tetrahedron Letters, 2010, vol. 51, # 25, p. 3259 - 3262]

31
[ 14068-53-2 ]
[ 1623-93-4 ]
[ 1296884-91-7 ]

Yield	Reaction Conditions	Operation in experiment
43%	With pyridine at 20℃; for 4h;	N-(5-Ethyl-1,3,4-thiadiazol-2-yl)biphenyl-4-sulfonamide (42). General procedure: To a solution of p-phenylbenzenesulfonyl chloride (250 mg, 0.99 mmol) in pyridine (5 mL) was added 2-amino-1,3,4-thiadiazole (100 mg, 0.99 mmol) at rt. The reaction mixture was stirred for 4 h, then 2 M HCl (20 mL) was added to quench the reaction. The mixture was extracted with EtOAc (3×30 mL), the organic layer was washed with water (30 mL) and brine (30 mL), dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was subjected to chromatography on silica gel (70-230 mesh) eluted with CH2Cl2:MeOH 19:1 to give the product 41 (178 mg, 0.56 mmol, 57% yield),

Reference： [1]Ahad, Ali Md.; Zuohe, Song; Du-Cuny, Lei; Moses, Sylvestor A.; Zhou, Li Li; Zhang, Shuxing; Powis, Garth; Meuillet, Emmanuelle J.; Mash, Eugene A. [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 6, p. 2046 - 2054]

32
[ 14068-53-2 ]
[ 57709-49-6 ]

Yield	Reaction Conditions	Operation in experiment
50%	With n-Amyl nitrite; copper(ll) bromide In ISOPROPYLAMIDE; acetonitrile at 20℃; for 2h;	20.1 To a solution of 2-amino-5-ethyl-1,3,4-thiadiazole (1.00 g) in acetonitrile (20 mL)/dimethylacetamide (20 mL) were added copper (II) bromide (2.07 g) and n-amyl nitrite (1.40 mL), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and to the residue was added a saturated aqueous ammonium chloride solution, and then the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and brine, dried over magnesium sulfate and then filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by column chromatography on silica gel (solvent; hexane/ethyl acetate = 95/5 to 80/20) to give 2-bromo-5-ethyl-1,3,4-thiadiazole (0.75 g) as a colorless liquid (yield: 50%). MS(APCI)m/z; 193/195[M+H]+.

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - EP2390254, 2011, A1 Location in patent: Page/Page column 61-62

33
[ 14068-53-2 ]
C₁₇H₁₈ClNO₃S [ No CAS ]
[ 1201912-26-6 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine at 25℃;	N-(2,3-Dihydro-1,4-benzodioxin-6-yl)-3-[4-[(2-phenylethyl)aminosulfonyl]-phenyl]propanamide (1): General procedure: A mixture of yellow oil thus obtained, 2,3-dihydrobenzo[b][1,4]dioxin-6-amine (0.15 g, 1 mmol), and pyridine (5 mL) was stirred overnight at 25 °C, poured into H2O (30 mL), and extracted with CH2Cl2 (30 mL x 3). The combined organic layer was washed with water, dried, filtered, and condensed. The residue was purified by flash chromatography on silica gel (200-300 mesh), eluted with a mixture of EtOAc/petroleum ether (1:1, v/v), to afford 1 (280 mg) as a white solid, yield 61%. Mp 132-134 °C; 1H-NMR (CDCl3, 400 MHz): δ 2.64 (t, J=7.5 Hz, 2H), 2.77 (t, J=6.9 Hz, 2H), 3.12 (t, J=7.5 Hz, 2H), 3.23 (t, J=6.9 Hz, 2H), 4.23 (m, 4H), 4.36 (br, 1H, -NH), 6.78 (d, J=8.7 Hz, 1H), 6.83 (dd, J1=8.7 Hz and J2=2.3 Hz, 1H), 7.01 (br, 1H, -NH), 7.08 (m, 3H), 7.28 (m, 3H), 7.36 (d, J=8.2 Hz, 2H), 7.71 (d, J=8.2 Hz, 2H); MS (EI) m/z 466 (M+); HRMS (EI) m/z calcd C25H26N2O5S (M+) 466.1562, found 466.1559.

Reference： [1]Huang, Huang; Lu, Weiqiang; Li, Xi; Cong, Xiaoli; Ma, Hongmei; Liu, Xiaofeng; Zhang, Yu; Che, Peng; Ma, Ruoqun; Li, Honglin; Shen, Xu; Jiang, Hualiang; Huang, Jin; Zhu, Jin [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 2, p. 958 - 962]

34
[ 14068-53-2 ]
C₁₅H₁₂Cl₂FNO₃S [ No CAS ]
[ 1357115-94-6 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine at 25℃;	N-(2,3-Dihydro-1,4-benzodioxin-6-yl)-3-[4-[(2-phenylethyl)aminosulfonyl]-phenyl]propanamide (1): General procedure: A mixture of yellow oil thus obtained, 2,3-dihydrobenzo[b][1,4]dioxin-6-amine (0.15 g, 1 mmol), and pyridine (5 mL) was stirred overnight at 25 °C, poured into H2O (30 mL), and extracted with CH2Cl2 (30 mL x 3). The combined organic layer was washed with water, dried, filtered, and condensed. The residue was purified by flash chromatography on silica gel (200-300 mesh), eluted with a mixture of EtOAc/petroleum ether (1:1, v/v), to afford 1 (280 mg) as a white solid, yield 61%. Mp 132-134 °C; 1H-NMR (CDCl3, 400 MHz): δ 2.64 (t, J=7.5 Hz, 2H), 2.77 (t, J=6.9 Hz, 2H), 3.12 (t, J=7.5 Hz, 2H), 3.23 (t, J=6.9 Hz, 2H), 4.23 (m, 4H), 4.36 (br, 1H, -NH), 6.78 (d, J=8.7 Hz, 1H), 6.83 (dd, J1=8.7 Hz and J2=2.3 Hz, 1H), 7.01 (br, 1H, -NH), 7.08 (m, 3H), 7.28 (m, 3H), 7.36 (d, J=8.2 Hz, 2H), 7.71 (d, J=8.2 Hz, 2H); MS (EI) m/z 466 (M+); HRMS (EI) m/z calcd C25H26N2O5S (M+) 466.1562, found 466.1559.

Reference： [1]Huang, Huang; Lu, Weiqiang; Li, Xi; Cong, Xiaoli; Ma, Hongmei; Liu, Xiaofeng; Zhang, Yu; Che, Peng; Ma, Ruoqun; Li, Honglin; Shen, Xu; Jiang, Hualiang; Huang, Jin; Zhu, Jin [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 2, p. 958 - 962]

35
[ 14068-53-2 ]
C₁₅H₁₃ClFNO₃S [ No CAS ]
[ 1201912-33-5 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine at 25℃;	N-(2,3-Dihydro-1,4-benzodioxin-6-yl)-3-[4-[(2-phenylethyl)aminosulfonyl]-phenyl]propanamide (1): General procedure: A mixture of yellow oil thus obtained, 2,3-dihydrobenzo[b][1,4]dioxin-6-amine (0.15 g, 1 mmol), and pyridine (5 mL) was stirred overnight at 25 °C, poured into H2O (30 mL), and extracted with CH2Cl2 (30 mL x 3). The combined organic layer was washed with water, dried, filtered, and condensed. The residue was purified by flash chromatography on silica gel (200-300 mesh), eluted with a mixture of EtOAc/petroleum ether (1:1, v/v), to afford 1 (280 mg) as a white solid, yield 61%. Mp 132-134 °C; 1H-NMR (CDCl3, 400 MHz): δ 2.64 (t, J=7.5 Hz, 2H), 2.77 (t, J=6.9 Hz, 2H), 3.12 (t, J=7.5 Hz, 2H), 3.23 (t, J=6.9 Hz, 2H), 4.23 (m, 4H), 4.36 (br, 1H, -NH), 6.78 (d, J=8.7 Hz, 1H), 6.83 (dd, J1=8.7 Hz and J2=2.3 Hz, 1H), 7.01 (br, 1H, -NH), 7.08 (m, 3H), 7.28 (m, 3H), 7.36 (d, J=8.2 Hz, 2H), 7.71 (d, J=8.2 Hz, 2H); MS (EI) m/z 466 (M+); HRMS (EI) m/z calcd C25H26N2O5S (M+) 466.1562, found 466.1559.

Reference： [1]Huang, Huang; Lu, Weiqiang; Li, Xi; Cong, Xiaoli; Ma, Hongmei; Liu, Xiaofeng; Zhang, Yu; Che, Peng; Ma, Ruoqun; Li, Honglin; Shen, Xu; Jiang, Hualiang; Huang, Jin; Zhu, Jin [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 2, p. 958 - 962]

36
[ 14068-53-2 ]
[ 5429-56-1 ]
[ 1215269-97-8 ]

Yield	Reaction Conditions	Operation in experiment
40%	With 1-hydroxy-pyrrolidine-2,5-dione; dicyclohexyl-carbodiimide In ethyl acetate at -10 - 20℃; for 24h;

Reference： [1]Location in patent: experimental part Das-Evcimen, Net; Sarikaya, Mutlu; Gurkok, Gokce; Suzen, Sibel [Medicinal Chemistry Research, 2011, vol. 20, # 4, p. 453 - 460]

37
[ 14068-53-2 ]
[ 123-54-6 ]
C₉H₁₂N₄O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	Stage #1: 2-amino-5-ethyl-1,3,4-thiadiazole With hydrogenchloride; sodium nitrite In water at -10 - -5℃; for 0.5h; Stage #2: acetylacetone With sodium acetate In water at 20℃; for 3h;

Reference： [1]Jha, Anjali; Murthy; Sanyal; Durga [Medicinal Chemistry Research, 2012, vol. 21, # 9, p. 2548 - 2556]

38
[ 14068-53-2 ]
[ 109-77-3 ]
C₇H₆N₆S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	Stage #1: 2-amino-5-ethyl-1,3,4-thiadiazole With hydrogenchloride; sodium nitrite In water at -10 - -5℃; for 0.5h; Stage #2: malononitrile With sodium acetate In water at 20℃; for 3h;

Reference： [1]Jha, Anjali; Murthy; Sanyal; Durga [Medicinal Chemistry Research, 2012, vol. 21, # 9, p. 2548 - 2556]

39
[ 14068-53-2 ]
[ 5470-18-8 ]
[ 1420066-38-1 ]

Yield	Reaction Conditions	Operation in experiment
52%	In toluene at 140℃; for 16h; Sealed tube;	2 4.7. Preparation of compounds 9a and 9b 4.7.2. 5-Ethyl-N-(5-ethyl-3-(3-nitropyridin-2-yl)-1,3,4-thiadiazol-2(3H)-ylidene)-1,3,4-thiadiazol-2-amine (9b). A mixture of 2-chloro-3-nitropyridine 6a (244 mg, 1.54 mmol) and 5-ethyl-1,3,4-thiadiazol-2-amine 2a (200 mg, 1.54 mmol) in toluene (1.5 ml) was stirred at 140 °C in a sealed tube for 16 h. The mixture was allowed to cool to room temperature, diluted (DCM), washed (satd NaHCO3), dried (filtered through a Biotage phase separator), and concentrated. The residue was purified by flash column chromatography (SiO2, 90:10→50:50 petroleum ether/EtOAc). The purification afforded 146 mg (52% yield) of desired product. Yellow solid; mp 152-154 °C (MeOH); 1H NMR (400 MHz, DMSO-d6) δ 8.98 (dd, J=4.8, 1.6 Hz, 1H), 8.71 (dd, J=8.2, 1.6 Hz 1H), 7.93 (dd, J=8.2, 4.8 Hz, 1H), 3.01-2.93 (m, 4H), 1.31 (t, J=7.4 Hz, 3H), 1.26 (t, J=7.4 Hz, 3H); 13C NMR (100 MHz, DMSO-d6) δ 170.0, 167.8, 159.9, 159.5, 154.0, 141.8, 141.6, 136.0, 126.9, 24.5, 24.1, 14.3, 12.6; HPLC tR=1.32 min; HRMS (ESI) m/z calcd for C13H14N7O2S2 [M+H]+ 364.0645, found 364.0647.

Reference： [1]Mammoliti, Oscar; Quinton, Evelyne M.; Loones, Kristof T.J.; Nguyen, Anh Tho; Wouters, Johan; Van Lommen, Guy [Tetrahedron, 2013, vol. 69, # 5, p. 1669 - 1680]

40
[ 14068-53-2 ]
[ 5470-18-8 ]
[ 1368233-42-4 ]

Yield	Reaction Conditions	Operation in experiment
37%	With N-ethyl-N,N-diisopropylamine In toluene at 120℃; for 16h; Sealed tube;	1 Preparation of compounds 7a and 5b 4.5.1. 2-Ethyl-8-nitro-[1,2,4]triazolo[1,5-a]pyridine (7a). A mixture of 2-chloro-3-nitropyridine 6a (246 mg, 1.55 mmol), 5-ethyl-1,3,4-thiadiazol-2-amine 2a (100 mg, 0.77 mmol), and i-Pr2NEt (0.27 ml, 1.55 mmol) in toluene (0.77 ml) was stirred at 120 °C in a sealed tube for 16 h. The mixture was allowed to cool to room temperature, diluted (DCM), washed (satd NaHCO3), dried (filtered through a Biotage phase separator), and concentrated. The residue was purified by flash column chromatography (SiO2, 100:0→90:10 DCM/EtOAc) to afford 55 mg of compound 7a (37% yield). Beige solid; mp 161-162 °C; 1H NMR (400 MHz, DMSO-d6) δ 9.31 (dd, J=6.7, 1.1 Hz, 1H), 8.62 (dd, J=7.9, 1.1 Hz, 1H), 7.33 (dd, J=7.9, 6.7 Hz, 1H), 2.94 (q, J=7.6 Hz, 2H), 1.36 (t, J=7.6 Hz, 3H); 13C NMR (100 MHz, DMSO-d6) δ 170.2, 145.2, 135.9, 135.6, 129.3, 112.3, 22.1, 12.6; HPLC tR=0.88 min; HRMS (ESI) m/z calcd for C8H9N4O2 [M+H]+ 193.0720, found 193.0730.

Reference： [1]Mammoliti, Oscar; Quinton, Evelyne M.; Loones, Kristof T.J.; Nguyen, Anh Tho; Wouters, Johan; Van Lommen, Guy [Tetrahedron, 2013, vol. 69, # 5, p. 1669 - 1680]

41
[ 14068-53-2 ]
[ 5470-18-8 ]
[ 1368233-42-4 ]
[ 52597-34-9 ]

Yield	Reaction Conditions	Operation in experiment
1: 17% 2: 4%	With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 120℃; for 16h; Sealed tube;	2 4.5. Preparation of compounds 7a and 5b 4.5.2. Bis(3-nitropyridin-2-yl)sulfane (5b). A mixture of 2-chloro-3-nitropyridine 6a (1.47 g, 9.29 mmol), 5-ethyl-1,3,4-thiadiazol-2-amine 2a (600 mg, 4.65 mmol), and i-Pr2NEt (1.60 ml, 4.64 mmol) in NMP (4.6 ml) was stirred at 120 °C in a sealed tube for 16 h. The mixture was allowed to cool to room temperature, diluted (DCM), washed (satd NaHCO3), dried (filtered through a Biotage phase separator), and concentrated. The residue was purified by flash column chromatography (SiO2, 50:50→70:30 EtOAc/petroleum ether and then 100:0→95:5 DCM/MeOH) to afford 55 mg of compound 5b (4% yield). Also 150 mg of 7a were obtained (17% yield). Compound 5b: yellow solid; mp 165-168 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.73 (dd, J=4.7, 1.6 Hz, 2H), 8.63 (dd, J=8.2, 1.6 Hz, 2H), 7.66 (dd, J=8.2, 4.7 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ 154.1, 150.3, 146.1, 134.6, 124.1; HPLC tR=1.20 min; HRMS (ESI) m/z calcd for C10H7N4O4S [M+H]+ 279.0183, found 279.0187.

Reference： [1]Mammoliti, Oscar; Quinton, Evelyne M.; Loones, Kristof T.J.; Nguyen, Anh Tho; Wouters, Johan; Van Lommen, Guy [Tetrahedron, 2013, vol. 69, # 5, p. 1669 - 1680]

42
[ 14068-53-2 ]
[ 364-73-8 ]
[ 1420066-24-5 ]

Yield	Reaction Conditions	Operation in experiment
32%	With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 140℃; for 16h; Sealed tube;	4.4. General procedure for synthesis of triazoles 4 General procedure: A mixture of 1 (1.55 mmol, unless otherwise stated), 2 (0.77 mmol), and i-Pr2NEt (1.55 mmol) in NMP (0.77 mL) was stirred at 140 °C in a sealed tube for 16 h. The mixture was allowed to cool to room temperature, diluted (DCM), washed (satd Na2CO3), dried (filtered through a Biotage phase separator), and concentrated. Purification method A: the residue was purifiedby reverse phase automated preparative HPLC. Purification method B: the residue was purified by flash column chromatography (SiO2).

Reference： [1]Mammoliti, Oscar; Quinton, Evelyne M.; Loones, Kristof T.J.; Nguyen, Anh Tho; Wouters, Johan; Van Lommen, Guy [Tetrahedron, 2013, vol. 69, # 5, p. 1669 - 1680]

43
[ 14068-53-2 ]
[ 20274-69-5 ]
[ 1420066-25-6 ]

Yield	Reaction Conditions	Operation in experiment
6%	With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 140℃; for 16h;Sealed tube;	General procedure: A mixture of 1 (1.55 mmol, unless otherwise stated), 2 (0.77 mmol), and i-Pr2NEt (1.55 mmol) in NMP (0.77 mL) was stirred at 140 C in a sealed tube for 16 h. The mixture was allowed to cool to room temperature, diluted (DCM), washed (satd Na2CO3), dried (filtered through a Biotage phase separator), and concentrated. Purification method A: the residue was purifiedby reverse phase automated preparative HPLC. Purification method B: the residue was purified by flash column chromatography (SiO2).

Reference： [1]Tetrahedron,2013,vol. 69,p. 1669 - 1680

44
[ 14068-53-2 ]
[ 364-74-9 ]
[ 1420066-26-7 ]

Yield	Reaction Conditions	Operation in experiment
78%	With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 140℃; for 16h;Sealed tube;	General procedure: A mixture of 1 (1.55 mmol, unless otherwise stated), 2 (0.77 mmol), and i-Pr2NEt (1.55 mmol) in NMP (0.77 mL) was stirred at 140 C in a sealed tube for 16 h. The mixture was allowed to cool to room temperature, diluted (DCM), washed (satd Na2CO3), dried (filtered through a Biotage phase separator), and concentrated. Purification method A: the residue was purifiedby reverse phase automated preparative HPLC. Purification method B: the residue was purified by flash column chromatography (SiO2).

Reference： [1]Tetrahedron,2013,vol. 69,p. 1669 - 1680

45
[ 14068-53-2 ]
[ 437-86-5 ]
[ 1420066-27-8 ]

Yield	Reaction Conditions	Operation in experiment
15%	With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 140℃; for 16h;Sealed tube;	General procedure: A mixture of 1 (1.55 mmol, unless otherwise stated), 2 (0.77 mmol), and i-Pr2NEt (1.55 mmol) in NMP (0.77 mL) was stirred at 140 °C in a sealed tube for 16 h. The mixture was allowed to cool to room temperature, diluted (DCM), washed (satd Na2CO3), dried (filtered through a Biotage® phase separator), and concentrated. Purification method A: the residue was purifiedby reverse phase automated preparative HPLC. Purification method B: the residue was purified by flash column chromatography (SiO2).

Reference： [1]Tetrahedron,2013,vol. 69,p. 1669 - 1680

46
[ 14068-53-2 ]
[ 4548-45-2 ]
[ 501918-16-7 ]

Yield	Reaction Conditions	Operation in experiment
37%	With N-ethyl-N,N-diisopropylamine In toluene at 120℃; for 16h; Sealed tube;	4.6. General procedure for synthesis of triazopyridines 7 General procedure: A mixture of 6 (1.55 mmol), 2 (0.77 mmol), and i-Pr2NEt(1.55 mmol) in toluene (unless otherwise stated) (0.77 ml) was stirred at 120 °C in a sealed tube for 16 h. The mixture was allowed to cool to room temperature. Purification method A: the mixture was concentrated and the residue was purified by reverse phase automatedpreparative HPLC. Purification method B: the mixture was concentrated and the residue was purified by flash column chromatography (SiO2). Purification method C: the mixture was diluted(DCM), washed (satd Na2CO3), dried (filtered through a Biotage phase separator), and concentrated. The residue was purified by reverse phase automated preparative HPLC.

Reference： [1]Mammoliti, Oscar; Quinton, Evelyne M.; Loones, Kristof T.J.; Nguyen, Anh Tho; Wouters, Johan; Van Lommen, Guy [Tetrahedron, 2013, vol. 69, # 5, p. 1669 - 1680]

47
[ 14068-53-2 ]
[ 21427-62-3 ]
[ 1420066-35-8 ]

Yield	Reaction Conditions	Operation in experiment
19%	With N-ethyl-N,N-diisopropylamine; In toluene; at 120℃; for 16h;Sealed tube;	General procedure: A mixture of 6 (1.55 mmol), 2 (0.77 mmol), and i-Pr2NEt(1.55 mmol) in toluene (unless otherwise stated) (0.77 ml) was stirred at 120 C in a sealed tube for 16 h. The mixture was allowed to cool to room temperature. Purification method A: the mixture was concentrated and the residue was purified by reverse phase automatedpreparative HPLC. Purification method B: the mixture was concentrated and the residue was purified by flash column chromatography (SiO2). Purification method C: the mixture was diluted(DCM), washed (satd Na2CO3), dried (filtered through a Biotage phase separator), and concentrated. The residue was purified by reverse phase automated preparative HPLC.

Reference： [1]Tetrahedron,2013,vol. 69,p. 1669 - 1680

48
[ 14068-53-2 ]
[ 886365-00-0 ]
[ 1420066-36-9 ]

Yield	Reaction Conditions	Operation in experiment
22%	With N-ethyl-N,N-diisopropylamine; In toluene; at 120.0℃; for 16.0h;Sealed tube;	General procedure: A mixture of 6 (1.55 mmol), 2 (0.77 mmol), and i-Pr2NEt(1.55 mmol) in toluene (unless otherwise stated) (0.77 ml) was stirred at 120 C in a sealed tube for 16 h. The mixture was allowed to cool to room temperature. Purification method A: the mixture was concentrated and the residue was purified by reverse phase automatedpreparative HPLC. Purification method B: the mixture was concentrated and the residue was purified by flash column chromatography (SiO2). Purification method C: the mixture was diluted(DCM), washed (satd Na2CO3), dried (filtered through a Biotage phase separator), and concentrated. The residue was purified by reverse phase automated preparative HPLC.

Reference： [1]Tetrahedron,2013,vol. 69,p. 1669 - 1680

49
[ 14068-53-2 ]
[ 1493-27-2 ]
[ 22100-66-9 ]
[ 1260489-09-5 ]
[ 1420066-18-7 ]

Yield	Reaction Conditions	Operation in experiment
1: 21% 2: 48% 3: 1%	With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one at 140℃; for 16h; Sealed tube;	4.3. Preparation of compounds 3, 4a, and 5a 4.3.2. 3-Ethyl-1-(2-nitrophenyl)-1H-1,2,4-triazol-5-amine (4a) and bis(2-nitrophenyl)sulfane (5a). A mixture of 1-fluoro-2-nitrobenzene 1a (489 ml, 4.64 mmol), 5-ethyl-1,3,4-thiadiazol-2-amine 2a (300 mg, 2.32 mmol), and i-Pr2NEt (0.81 ml,4.64 mmol) in NMP (2.3 ml) was stirred at 140 °C in a sealed tubefor 16 h. The mixture was allowed to cool to room temperature, diluted (DCM), washed (satd NaHCO3), dried (filtered through a Biotage phase separator), and concentrated. The residue was loaded on an ion exchange resin (Biotage SCX-3). The adsorbed material was first eluted with MeOH and then with 2 N NH3/MeOH. The first fraction was concentrated, diluted (EtOAc), washed(H2O×5), dried (Na2SO4), and concentrated. The residue was purifiedby flash column chromatography (SiO2, 2:98/20:80 EtOAc/petroleum ether) to afford 136 mg of compound 5a (21% yield). Also6 mg (1% yield) of 3 were obtained. The second fraction was concentrated and purified by flash column chromatography (SiO2,50:50/100:0 EtOAc/petroleum ether) to afford 130 mg of compound4a (48% yield).

Reference： [1]Mammoliti, Oscar; Quinton, Evelyne M.; Loones, Kristof T.J.; Nguyen, Anh Tho; Wouters, Johan; Van Lommen, Guy [Tetrahedron, 2013, vol. 69, # 5, p. 1669 - 1680]

50
[ 14068-53-2 ]
[ 1493-27-2 ]
[ 1420066-37-0 ]

Yield	Reaction Conditions	Operation in experiment
9%	In 1-methyl-pyrrolidin-2-one at 140℃; for 16h; Sealed tube;	1 Preparation of compounds 9a and 9b 4.7.1. 5-Ethyl-N-(5-ethyl-3-(2-nitrophenyl)-1,3,4-thiadiazol-2(3H)-ylidene)-1,3,4-thiadiazol-2-amine (9a). A mixture of 1-fluoro-2-nitrobenzene 1a (100 mg, 0.71 mmol) and 5-ethyl-1,3,4-thiadiazol-2-amine 2a (92 mg, 0.71 mmol) in NMP (0.5 ml) was stirred at 140 °C in a sealed tube for 16 h. The reaction was stopped and the mixture was purified by automated preparative HPLC. The purification afforded 11 mg (9% yield) of desired product. Yellow solid; 164-166 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.18 (dd, J=8.1, 1.3 Hz, 1H), 7.98-7.94 (m, 1H), 7.90 (dd, J=8.1, 1.5 Hz, 1H), 7.79 (ddd, J=8.1, 7.3, 1.5 Hz, 1H), 2.98-2.92 (m, 4H), 1.30 (t, J=7.5 Hz, 3H), 1.26 (t, J=7.6 Hz, 3H); 13C NMR (100 MHz, DMSO-d6) δ 170.4, 167.2, 159.4, 159.4, 144.9, 135.1, 130.9, 130.8, 129.8, 125.8, 24.3, 24.0, 14.2, 12.6; HPLC tR=1.44 min; HRMS (ESI) m/z calcd for C14H15N6O2S2 [M+H]+ 363.0692, found 363.0712.

Reference： [1]Mammoliti, Oscar; Quinton, Evelyne M.; Loones, Kristof T.J.; Nguyen, Anh Tho; Wouters, Johan; Van Lommen, Guy [Tetrahedron, 2013, vol. 69, # 5, p. 1669 - 1680]

51
[ 14068-53-2 ]
[ 1493-27-2 ]
[ 1260489-09-5 ]

Yield	Reaction Conditions	Operation in experiment
29%	With caesium carbonate In 1,4-dioxane at 100℃; for 1h;	1 Preparation of compounds 3, 4a, and 5a 4.3.1. 5-Ethyl-N-(2-nitrophenyl)-1,3,4-thiadiazol-2-amine (3). A mixture of 1-fluoro-2-nitrobenzene 1a (1.00 g, 7.09 mmol), 5-ethyl-1,3,4-thiadiazol-2-amine 2a (1.10 g, 8.52 mmol), and Cs2CO3 (2.30 g, 7.04 mmol) in 1,4-dioxane (15 ml) was stirred at 100 °C in a round bottomed flask for 1 h. The mixture was diluted (EtOAc), washed (0.5 N HCl, satd NaHCO3 and H2O), dried (Na2SO4), and concentrated. The residue was purified by flash column chromatography (SiO2, 95:5→70:30 petroleum ether/EtOAc) to afford 520 mg (29% yield) of desired product. Orange solid; mp 84-86 °C; 1H NMR (400 MHz, CDCl3) δ 10.62 (s, 1H), 8.74 (dd, J=8.6, 1.0 Hz, 1H), 8.27 (dd, J=8.4, 1.5 Hz, 1H), 7.69-7.65 (m, 1H), 7.11-7.07 (m, 1H), 3.06 (q, J=7.6 Hz, 2H), 1.42 (t, J=7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 165.3, 162.6, 137.3, 136.6, 134.5, 126.2, 121.4, 119.9, 24.0, 13.9; HPLC tR=1.24 min; HRMS (ESI) m/z calcd for C10H11N4O2S [M+H]+ 251.0597, found 251.0615.

Reference： [1]Mammoliti, Oscar; Quinton, Evelyne M.; Loones, Kristof T.J.; Nguyen, Anh Tho; Wouters, Johan; Van Lommen, Guy [Tetrahedron, 2013, vol. 69, # 5, p. 1669 - 1680]

52
[ 14068-53-2 ]
(2R,3S)-2-hydroxy-3-{3-(N-methylmethanesulfonamido)-5-[(R)-1-phenylethylcarbamoyl]benzamido}-4-phenylbutanoic acid [ No CAS ]
N₁-[(2S,3R)-4-(5-ethyl-1,3,4-thiadiazol-2-ylamino)-3-hydroxy-4-oxo-1-phenylbutan-2-yl]-5-(N-methylmethanesulfonamido)-N₃-[(R)-1-phenylethyl]isophthalamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0 - 20℃; for 12h;	5.1.1. General procedure for coupling reaction (A) General procedure: Carboxylic acid (1.0 mmol), HOBt·H2O (1.1 mmol), and amine (1.1 mmol) were dissolved in DMF; the reaction mixture was cooled to 0 °C and stirred. After 15 min, EDC·HCl (1.5 mmol) was added. The reaction was stirred for 12 h at room temperature. After removal of the solvent in vacuo, the residue was dissolved in EtOAc, and washed with 10% citric acid (aq), 5% NaHCO3 (aq), and brine. The organic layer was dried over anhydrous magnesium sulfate (MgSO4), and the filtrate was concentrated to give the crude product that was further purified by column chromatography or purified by preparative HPLC in case of the target compounds. The purified target compounds were immediately lyophilized to afford their respective amorphous powders.

Reference： [1]Suzuki, Kenji; Hamada, Yoshio; Nguyen, Jeffrey-Tri; Kiso, Yoshiaki [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6665 - 6673]

53
[ 14068-53-2 ]
[ 37517-81-0 ]
C₈H₉N₃O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 2-chloro-1,3-dimethyl imidazolium chloride; N-ethyl-N,N-diisopropylamine In 1,2-dichloro-ethane; acetonitrile at 20℃; for 3h;	General procedure: To 2-amino-5-ethyl-1,3,4-thiadiazole (200 mg, 1.55 mmol) in CH3CN (4 ml)/DCE (4 ml) was added 3-ethoxy-2-fluoro-3-oxopropanoic acid (279 mg, 1.86 mmol) followed byi-Pr2NEt (0.81 ml, 4.64 mmol) and 2-chloro-1,3-dimethylimidazolidinium chloride (336 mg, 2.01 mmol). The mixture stirred at r.t. for 3 h. The mixture was transferred to a microwave vial and POCl3(1.44 ml, 15.48 mmol) was added. The mixture was then heated in the microwave at 150 °C for 10 min. Upon completion, the mixture was concentrated in vacuo and taken up in CDCl3. It was then washed with sat. aq. NaHCO3solution, water and brine, dried over Na2SO4. After the removal of organic solventin vacuo, the residue was purified through Biotage chromatography (EtOAc/DCM: 0-10% gradient) to give the desired product (170 mg, 47%) as a yellow solid. Analogue6was obtained by following the procedure as the synthesis of analogue1(RUC1).

Reference： [1]Jiang, Jian-Kang; McCoy, Joshua G.; Shen, Min; LeClair, Christopher A.; Huang, Wenwei; Negri, Ana; Li, Jihong; Blue, Robert; Harrington, Amanda Weil; Naini, Sarasija; David III, George; Choi, Won-Seok; Volpi, Elisabetta; Fernandez, Joseph; Babayeva, Mariana; Nedelman, Mark A.; Filizola, Marta; Coller, Barry S.; Thomas, Craig J. [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 4, p. 1148 - 1153]

54
[ 14068-53-2 ]
[ 100701-49-3 ]
C₉H₁₀FN₃O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 2-chloro-1,3-dimethyl imidazolium chloride; N-ethyl-N,N-diisopropylamine In 1,2-dichloro-ethane; acetonitrile at 20℃; for 3h;	To 2-amino-5-ethyl-1,3,4-thiadiazole (200 mg, 1.55 mmol) in CH3CN (4 ml)/DCE (4 ml) was added 3-ethoxy-2-fluoro-3-oxopropanoic acid (279 mg, 1.86 mmol) followed byi-Pr2NEt (0.81 ml, 4.64 mmol) and 2-chloro-1,3-dimethylimidazolidinium chloride (336 mg, 2.01 mmol). The mixture stirred at r.t. for 3 h. The mixture was transferred to a microwave vial and POCl3(1.44 ml, 15.48 mmol) was added. The mixture was then heated in the microwave at 150 °C for 10 min. Upon completion, the mixture was concentrated in vacuo and taken up in CDCl3. It was then washed with sat. aq. NaHCO3solution, water and brine, dried over Na2SO4. After the removal of organic solventin vacuo, the residue was purified through Biotage chromatography (EtOAc/DCM: 0-10% gradient) to give the desired product (170 mg, 47%) as a yellow solid. Analogue6was obtained by following the procedure as the synthesis of analogue1(RUC1).

Reference： [1]Jiang, Jian-Kang; McCoy, Joshua G.; Shen, Min; LeClair, Christopher A.; Huang, Wenwei; Negri, Ana; Li, Jihong; Blue, Robert; Harrington, Amanda Weil; Naini, Sarasija; David III, George; Choi, Won-Seok; Volpi, Elisabetta; Fernandez, Joseph; Babayeva, Mariana; Nedelman, Mark A.; Filizola, Marta; Coller, Barry S.; Thomas, Craig J. [Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 4, p. 1148 - 1153]

55
[ 14068-53-2 ]
[ 459-57-4 ]
[ 1422676-22-9 ]

Yield	Reaction Conditions	Operation in experiment
92.8%	With triethylamine In N,N-dimethyl-formamide at 85℃; for 10h;

Reference： [1]Liu, Yu-Ting; Feng, Li; Yin, Da-Wei; Su, Bao-Jun [Research on Chemical Intermediates, 2014, vol. 40, # 4, p. 1607 - 1612]

56
[ 14068-53-2 ]
[ 1621526-53-1 ]
[ 1621526-33-7 ]

Yield	Reaction Conditions	Operation in experiment
74%	Stage #1: 2-(2-(4-bromophenyl)-3,5-diphenyl-1H-pyrrol-1-yl)acetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 0.0833333h; Inert atmosphere; Stage #2: 2-amino-5-ethyl-1,3,4-thiadiazole With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 3h; Inert atmosphere;	4.3 General procedure for the preparation of 1,2,3,5-tetrasubstituted pyrrolyl-N-acetamide derivatives General procedure: Compound 4 (1mmol) was dissolved in freshly dry dichloromethane under nitrogen atmosphere. Then HOBt (1.1mmol), EDC.HCl (1.1mmol) were added to the above solution. The resulting mixture was stirred for 5min, and then amine (R4) (1.2mmol) was added slowly followed by N,N-diisopropylethylamine (DIPEA) (1.2mmol). The mixture was allowed to stir for 3h at room temperature. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was quenched with water (10-15mL) and extracted with dichloromethane. The organic layer was collected and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure and the resultant crude material was purified by column chromatography.

Reference： [1]Pagadala, Lakshmi Reddy; Mukkara, Lakshmi Devi; Singireddi, Satyanarayana; Singh, Ashita; Thummaluru, Veera Reddy; Jagarlamudi, Padma Sridevi; Guttala, Raja Sekhar; Perumal, Yogeeswari; Dharmarajan, Sriram; Upadhyayula, Suryanarayana Murty; Ummanni, Ramesh; Basireddy, Venkata Subba Reddy; Ravirala, Narender [European Journal of Medicinal Chemistry, 2014, vol. 84, p. 118 - 126]

57
[ 14068-53-2 ]
[ 1621526-42-8 ]
[ 1621526-16-6 ]

Yield	Reaction Conditions	Operation in experiment
81%	Stage #1: 2-(2-(furan-2-yl)-3,5-diphenyl-1H-pyrrol-1-yl)acetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 0.0833333h; Inert atmosphere; Stage #2: 2-amino-5-ethyl-1,3,4-thiadiazole With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 3h; Inert atmosphere;	4.3 General procedure for the preparation of 1,2,3,5-tetrasubstituted pyrrolyl-N-acetamide derivatives General procedure: Compound 4 (1mmol) was dissolved in freshly dry dichloromethane under nitrogen atmosphere. Then HOBt (1.1mmol), EDC.HCl (1.1mmol) were added to the above solution. The resulting mixture was stirred for 5min, and then amine (R4) (1.2mmol) was added slowly followed by N,N-diisopropylethylamine (DIPEA) (1.2mmol). The mixture was allowed to stir for 3h at room temperature. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was quenched with water (10-15mL) and extracted with dichloromethane. The organic layer was collected and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure and the resultant crude material was purified by column chromatography.

Reference： [1]Pagadala, Lakshmi Reddy; Mukkara, Lakshmi Devi; Singireddi, Satyanarayana; Singh, Ashita; Thummaluru, Veera Reddy; Jagarlamudi, Padma Sridevi; Guttala, Raja Sekhar; Perumal, Yogeeswari; Dharmarajan, Sriram; Upadhyayula, Suryanarayana Murty; Ummanni, Ramesh; Basireddy, Venkata Subba Reddy; Ravirala, Narender [European Journal of Medicinal Chemistry, 2014, vol. 84, p. 118 - 126]

58
[ 14068-53-2 ]
[ 1621526-50-8 ]
[ 1621526-37-1 ]

Yield	Reaction Conditions	Operation in experiment
83%	Stage #1: C₂₆H₁₉NO₃ With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 0.0833333h; Inert atmosphere; Stage #2: 2-amino-5-ethyl-1,3,4-thiadiazole With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 3h; Inert atmosphere;	4.3 General procedure for the preparation of 1,2,3,5-tetrasubstituted pyrrolyl-N-acetamide derivatives General procedure: Compound 4 (1mmol) was dissolved in freshly dry dichloromethane under nitrogen atmosphere. Then HOBt (1.1mmol), EDC.HCl (1.1mmol) were added to the above solution. The resulting mixture was stirred for 5min, and then amine (R4) (1.2mmol) was added slowly followed by N,N-diisopropylethylamine (DIPEA) (1.2mmol). The mixture was allowed to stir for 3h at room temperature. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was quenched with water (10-15mL) and extracted with dichloromethane. The organic layer was collected and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure and the resultant crude material was purified by column chromatography.

Reference： [1]Pagadala, Lakshmi Reddy; Mukkara, Lakshmi Devi; Singireddi, Satyanarayana; Singh, Ashita; Thummaluru, Veera Reddy; Jagarlamudi, Padma Sridevi; Guttala, Raja Sekhar; Perumal, Yogeeswari; Dharmarajan, Sriram; Upadhyayula, Suryanarayana Murty; Ummanni, Ramesh; Basireddy, Venkata Subba Reddy; Ravirala, Narender [European Journal of Medicinal Chemistry, 2014, vol. 84, p. 118 - 126]

59
[ 14068-53-2 ]
2-(2-(furan-2-yl)-3-(naphthalene-1-yl)-5-phenyl-1H-pyrrol-1-yl)acetic acid [ No CAS ]
[ 1621526-40-6 ]

Yield	Reaction Conditions	Operation in experiment
83%	Stage #1: 2-(2-(furan-2-yl)-3-(naphthalene-1-yl)-5-phenyl-1H-pyrrol-1-yl)acetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 0.0833333h; Inert atmosphere; Stage #2: 2-amino-5-ethyl-1,3,4-thiadiazole With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 3h; Inert atmosphere;	4.3 General procedure for the preparation of 1,2,3,5-tetrasubstituted pyrrolyl-N-acetamide derivatives General procedure: Compound 4 (1mmol) was dissolved in freshly dry dichloromethane under nitrogen atmosphere. Then HOBt (1.1mmol), EDC.HCl (1.1mmol) were added to the above solution. The resulting mixture was stirred for 5min, and then amine (R4) (1.2mmol) was added slowly followed by N,N-diisopropylethylamine (DIPEA) (1.2mmol). The mixture was allowed to stir for 3h at room temperature. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was quenched with water (10-15mL) and extracted with dichloromethane. The organic layer was collected and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure and the resultant crude material was purified by column chromatography.

Reference： [1]Pagadala, Lakshmi Reddy; Mukkara, Lakshmi Devi; Singireddi, Satyanarayana; Singh, Ashita; Thummaluru, Veera Reddy; Jagarlamudi, Padma Sridevi; Guttala, Raja Sekhar; Perumal, Yogeeswari; Dharmarajan, Sriram; Upadhyayula, Suryanarayana Murty; Ummanni, Ramesh; Basireddy, Venkata Subba Reddy; Ravirala, Narender [European Journal of Medicinal Chemistry, 2014, vol. 84, p. 118 - 126]

60
[ 14068-53-2 ]
[ 59214-56-1 ]
[ 1621526-25-7 ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: 2-(2,3,5-triphenyl-1H-pyrrol-1-yl)acetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 0.0833333h; Inert atmosphere; Stage #2: 2-amino-5-ethyl-1,3,4-thiadiazole With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 3h; Inert atmosphere;	4.3 General procedure for the preparation of 1,2,3,5-tetrasubstituted pyrrolyl-N-acetamide derivatives General procedure: Compound 4 (1mmol) was dissolved in freshly dry dichloromethane under nitrogen atmosphere. Then HOBt (1.1mmol), EDC.HCl (1.1mmol) were added to the above solution. The resulting mixture was stirred for 5min, and then amine (R4) (1.2mmol) was added slowly followed by N,N-diisopropylethylamine (DIPEA) (1.2mmol). The mixture was allowed to stir for 3h at room temperature. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was quenched with water (10-15mL) and extracted with dichloromethane. The organic layer was collected and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure and the resultant crude material was purified by column chromatography.

Reference： [1]Pagadala, Lakshmi Reddy; Mukkara, Lakshmi Devi; Singireddi, Satyanarayana; Singh, Ashita; Thummaluru, Veera Reddy; Jagarlamudi, Padma Sridevi; Guttala, Raja Sekhar; Perumal, Yogeeswari; Dharmarajan, Sriram; Upadhyayula, Suryanarayana Murty; Ummanni, Ramesh; Basireddy, Venkata Subba Reddy; Ravirala, Narender [European Journal of Medicinal Chemistry, 2014, vol. 84, p. 118 - 126]

61
[ 14068-53-2 ]
[ 1621526-47-3 ]
[ 1621526-31-5 ]

Yield	Reaction Conditions	Operation in experiment
83%	Stage #1: 2-(2,3-di(furan-2-yl)-5-phenyl-1H-pyrrol-1-yl)acetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 0.0833333h; Inert atmosphere; Stage #2: 2-amino-5-ethyl-1,3,4-thiadiazole With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 3h; Inert atmosphere;	4.3 General procedure for the preparation of 1,2,3,5-tetrasubstituted pyrrolyl-N-acetamide derivatives General procedure: Compound 4 (1mmol) was dissolved in freshly dry dichloromethane under nitrogen atmosphere. Then HOBt (1.1mmol), EDC.HCl (1.1mmol) were added to the above solution. The resulting mixture was stirred for 5min, and then amine (R4) (1.2mmol) was added slowly followed by N,N-diisopropylethylamine (DIPEA) (1.2mmol). The mixture was allowed to stir for 3h at room temperature. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was quenched with water (10-15mL) and extracted with dichloromethane. The organic layer was collected and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure and the resultant crude material was purified by column chromatography.

Reference： [1]Pagadala, Lakshmi Reddy; Mukkara, Lakshmi Devi; Singireddi, Satyanarayana; Singh, Ashita; Thummaluru, Veera Reddy; Jagarlamudi, Padma Sridevi; Guttala, Raja Sekhar; Perumal, Yogeeswari; Dharmarajan, Sriram; Upadhyayula, Suryanarayana Murty; Ummanni, Ramesh; Basireddy, Venkata Subba Reddy; Ravirala, Narender [European Journal of Medicinal Chemistry, 2014, vol. 84, p. 118 - 126]

62
N-(9-(2-(chlorocarbonyl)phenyl)-6-(diethylamino)-3H-xanthen-3-ylidene)-N-ethylethanaminium chloride [ No CAS ]
[ 14068-53-2 ]
C₃₂H₃₅N₅O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.49 g	With triethylamine In acetonitrile for 24h; Reflux;	4.2. Synthesis and characterization General procedure: Through similar procedures as published in the literature, fourcompounds AeD was synthesized and showed the same meltingpoint as in the literature.38 Synthesis of compounds LI-L4,39 inbrief, to a stirred solution of rhodamine hydrochloride (1.0 g,2 mmol) and 2-dichloroethane (5 mL), phosphorus oxychloride(1 mL) was added. The solution was refluxed for 8 h and concentratedby evaporation. The obtained crude acid chloride was dissolvedin 10 mL acetonitrile. Then, a solution of the thiadiazolederivatives (4 mmol) and triethylamine (1 mL) in acetonitrile(10 mL) was added dropwise in 30 min and refluxed for 24 h. Aftercooling to room temperature, the resulting solution was pouredinto 50 mL cold water, and extracted with methylene chloride. Theorganic layer was washed with aqueous NaOH solution and driedover anhydrous MgSO4. Then the solvent was removed under reducedpressure and the residue was purified by silica gel column chromatography with DCM/PE (1:1, v/v) as eluent to give L1-L4.

Reference： [1]Meng, Wen-Fei; Yang, Mei-Pan; Li, Bo; Cheng, Zhao; Yang, Bing-Qin [Tetrahedron, 2014, vol. 70, # 45, p. 8577 - 8581]

63
[ 14068-53-2 ]
[ 100-52-7 ]
[ 36231-88-6 ]

Yield	Reaction Conditions	Operation in experiment
42%	With tert.-butylhydroperoxide; copper(l) iodide In neat (no solvent) at 20℃; for 12h;	General procedure: An aqueous solution of 70% TBHP (2.4 mmol) wasadded into a mixture of aldehyde 1(2.4 mmol), amine 2 (0.8 mmol), andCuI (0.08 mmol), then the mixture was stirred for 12 hours at room temperature.After that, the mixture was added with 6 mL saturated Na2CO3aqueous solution and extracted by EtOAc (10 mL× 3). The organic layer was washed by water, driedwith anhydroussodium sulfate, filtered, and followed by the removal of the solvent undervacuum. Finally, the product was purified by column chromatography on silica gel and eluted with petrolether/ethyl acetate (50/1 to 20/1) toafford the desired product 3.

Reference： [1]Ding, Yongzheng; Zhang, Xian; Zhang, Dongyang; Chen, Yuting; Wu, Zhibing; Wang, Peiyi; Xue, Wei; Song, Baoan; Yang, Song [Tetrahedron Letters, 2015, vol. 56, # 6, p. 831 - 833]

64
[ 98-01-1 ]
[ 14068-53-2 ]
N-(5-ethyl-1,3,4-thiadiazol-2-yl)furan-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	With tert.-butylhydroperoxide; copper(l) iodide In neat (no solvent) at 20℃; for 12h;	General procedure: An aqueous solution of 70% TBHP (2.4 mmol) wasadded into a mixture of aldehyde 1(2.4 mmol), amine 2 (0.8 mmol), andCuI (0.08 mmol), then the mixture was stirred for 12 hours at room temperature.After that, the mixture was added with 6 mL saturated Na2CO3aqueous solution and extracted by EtOAc (10 mL× 3). The organic layer was washed by water, driedwith anhydroussodium sulfate, filtered, and followed by the removal of the solvent undervacuum. Finally, the product was purified by column chromatography on silica gel and eluted with petrolether/ethyl acetate (50/1 to 20/1) toafford the desired product 3.

Reference： [1]Ding, Yongzheng; Zhang, Xian; Zhang, Dongyang; Chen, Yuting; Wu, Zhibing; Wang, Peiyi; Xue, Wei; Song, Baoan; Yang, Song [Tetrahedron Letters, 2015, vol. 56, # 6, p. 831 - 833]

65
[ 14068-53-2 ]
[ 78-84-2 ]
N-(5-ethyl-1,3,4-thiadiazol-2-yl)isobutyramide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With tert.-butylhydroperoxide; copper(l) iodide In neat (no solvent) at 20℃; for 12h;	General procedure: An aqueous solution of 70% TBHP (2.4 mmol) wasadded into a mixture of aldehyde 1(2.4 mmol), amine 2 (0.8 mmol), andCuI (0.08 mmol), then the mixture was stirred for 12 hours at room temperature.After that, the mixture was added with 6 mL saturated Na2CO3aqueous solution and extracted by EtOAc (10 mL× 3). The organic layer was washed by water, driedwith anhydroussodium sulfate, filtered, and followed by the removal of the solvent undervacuum. Finally, the product was purified by column chromatography on silica gel and eluted with petrolether/ethyl acetate (50/1 to 20/1) toafford the desired product 3.

Reference： [1]Ding, Yongzheng; Zhang, Xian; Zhang, Dongyang; Chen, Yuting; Wu, Zhibing; Wang, Peiyi; Xue, Wei; Song, Baoan; Yang, Song [Tetrahedron Letters, 2015, vol. 56, # 6, p. 831 - 833]

66
[ 14068-53-2 ]
[ 14949-01-0 ]
2-(5-ethyl-1,3,4-thiadiazol-2-ylamino)-N-(4-sulfamoylphenyl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With triethylamine In N,N-dimethyl-formamide for 17h; Reflux;	General procedure for the synthesis of sulfonamides(2-13) General procedure: A mixture of compound 1a (2.489 g, 0.01 mol) and required amines, namely: adamantylamine, 5-aminoindanone, 4-morpholinobenzamine, piperonylamine,2-amino-6-fluorobenzothiazole, 2-amino-6-ethoxybenzothiazole, 2-amino-5,6-dimethyl-benzothiazole,2-amino-1-ethylpyrazole, 2-amino-5-ethylthiadiazole, 2-amino-5-thioethylthiadiazole, 3-aminoquinoline and 2-aminoisoquinoline (0.01 mol) in dimethylformamide (20 mL) containing 3 drops of triethylamine was refluxed for 17 h. The reaction mixture was collected and poured onto ice/water. The obtained solid was recrystallized from dioxane to give derivatives 2-13, respectively.

Reference： [1]Ghorab, Mostafa M.; Alsaid, Mansour S.; Abdullah-al-dhfyan; Arafa, Reem K. [Acta poloniae pharmaceutica, 2015, vol. 72, # 1, p. 79 - 87]

67
[ 14068-53-2 ]
[ 113100-61-1 ]
1,3-dimethyl-N-(5-ethyl-1,3,4-thiadiazole-2-yl)-1H-pyrazole-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68.3%	With potassium carbonate In tetrahydrofuran at 5 - 20℃;	3.5. General Procedure for the Preparation of 7aa-bk General procedure: Pyrazole acid chlorides 6a-b were prepared by refluxing 4a-b in thionyl chloride for 8 h. Pyrazole acid chlorides 6a-b (12 mmol) in anhydrous tetrahydrofuran (THF; 30 mL) were slowly added to a solution of amine derivatives or 5-methylisoxazol-3-ol (10 mmol) and K2CO3 (1.38 g, 10 mmol) in anhydrous THF (30 mL) at a controlled temperature of 5 °C. The reaction proceeded at room temperature until 6a-b was no longer tested by TLC. The reaction solution was then filtered and the solvent distilled. The residue was dissolved in ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate and recrystallized to generate the target pyrazole carboxamides and isoxazolol pyrazole carboxylates (7aa-bk). The product yields ranged from 40% to 80%. All 20 compounds were novel, and the physical and spectral data for these compounds are listed below.
68.3%	With potassium carbonate In chloroform at 0 - 20℃; for 10h; Green chemistry;	12 Example 12 General procedure: In a 100 ml three-necked flask equipped with a thermometer and an electromagnetic stir bar were added 0.01 mol of anhydrous K2CO3 powder, 0.01 mol of 2-nitroaniline,30 ml of acetone,A solution prepared by dissolving 0.01 mol of 1,3-dimethyl-4-pyrazolecarboxylic acid chloride in 20 ml of acetone was gradually added dropwise at low temperature (0 to 5 ° C), and the reaction was continued at room temperature for 10 hours. The reaction mixture was filtered under reduced pressure, and the resulting filtrate was decompressed to yield a crude product of compound Q110907. The crude product of compound Q110907 was recrystallized from acetonitrile to give the compound (Q110907) in a yield of 42.9%. Using 2-amino-5-ethyl-3,4-thiadiazole instead of 2-nitroaniline; chloroform as the reaction solvent; ethanol recrystallization

Reference： [1]Sun, Jialong; Zhou, Yuanming [Molecules, 2015, vol. 20, # 3, p. 4383 - 4394]
[2]Current Patent Assignee: QINGDAO AGRICULTURAL UNIVERSITY - CN103524417, 2016, B Location in patent: Paragraph 0026; 0031

68
[ 14068-53-2 ]
[ 126674-98-4 ]
1-methyl-N-(5-ethyl-1,3,4-thiadiazole-2-yl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56.9%	With potassium carbonate In tetrahydrofuran at 5 - 20℃;	3.5. General Procedure for the Preparation of 7aa-bk General procedure: Pyrazole acid chlorides 6a-b were prepared by refluxing 4a-b in thionyl chloride for 8 h. Pyrazole acid chlorides 6a-b (12 mmol) in anhydrous tetrahydrofuran (THF; 30 mL) were slowly added to a solution of amine derivatives or 5-methylisoxazol-3-ol (10 mmol) and K2CO3 (1.38 g, 10 mmol) in anhydrous THF (30 mL) at a controlled temperature of 5 °C. The reaction proceeded at room temperature until 6a-b was no longer tested by TLC. The reaction solution was then filtered and the solvent distilled. The residue was dissolved in ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate and recrystallized to generate the target pyrazole carboxamides and isoxazolol pyrazole carboxylates (7aa-bk). The product yields ranged from 40% to 80%. All 20 compounds were novel, and the physical and spectral data for these compounds are listed below.

Reference： [1]Sun, Jialong; Zhou, Yuanming [Molecules, 2015, vol. 20, # 3, p. 4383 - 4394]

69
[ 75-15-0 ]
[ 14068-53-2 ]
manganese(ll) chloride [ No CAS ]
C₁₀H₁₂MnN₆S₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89.4%	Stage #1: carbon disulfide; 2-amino-5-ethyl-1,3,4-thiadiazole With sodium hydroxide In water at 30℃; for 2h; Green chemistry; Stage #2: manganese(ll) chloride In water Green chemistry;

Reference： [1]Yuting, Liu; Gangtao, Liang; Dawei, Yin [Journal of the Chemical Society of Pakistan, 2015, vol. 37, # 1, p. 115 - 121]

70
[ 824-42-0 ]
[ 14068-53-2 ]
C₁₂H₁₃N₃OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid In ethanol for 5h; Inert atmosphere; Reflux;	1.1 Synthesis of compounds 4c-4i General procedure: Under nitrogen, into a 100 mL flask were added 2-amino-5-methyl-1,3,4-thiadiazole (3.450 g, 0.03 mol),2-hydroxy-3-methylbenzaldehyde (4.896g, 0.036 mol) and anhydrous ethanol (60mL). Then, p-toluenesulfonic acid (0.570 g, 0.003 mmol) was added with stirring and the mixture was heated to reflux for about 5 h (checked by TLC).

Reference： [1]Tang, Zi-Long; Xia, Zan-Wen; Chang, Shu-Hong; Wang, Zhao-Xu [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 16, p. 3378 - 3381]

71
[ 14068-53-2 ]
[ 90-02-8 ]
2-[(Z)-5-Ethyl-[1,3,4]thiadiazol-2-ylimino]-methyl}-phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid In ethanol for 5h; Inert atmosphere; Reflux;	1.1 Synthesis of compounds 4c-4i General procedure: Under nitrogen, into a 100 mL flask were added 2-amino-5-methyl-1,3,4-thiadiazole (3.450 g, 0.03 mol),2-hydroxy-3-methylbenzaldehyde (4.896g, 0.036 mol) and anhydrous ethanol (60mL). Then, p-toluenesulfonic acid (0.570 g, 0.003 mmol) was added with stirring and the mixture was heated to reflux for about 5 h (checked by TLC).

Reference： [1]Tang, Zi-Long; Xia, Zan-Wen; Chang, Shu-Hong; Wang, Zhao-Xu [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 16, p. 3378 - 3381]

72
[ 14068-53-2 ]
[ 613-84-3 ]
C₁₂H₁₃N₃OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With toluene-4-sulfonic acid In ethanol for 5h; Inert atmosphere; Reflux;	1.1 Synthesis of compounds 4c-4i General procedure: Under nitrogen, into a 100 mL flask were added 2-amino-5-methyl-1,3,4-thiadiazole (3.450 g, 0.03 mol),2-hydroxy-3-methylbenzaldehyde (4.896g, 0.036 mol) and anhydrous ethanol (60mL). Then, p-toluenesulfonic acid (0.570 g, 0.003 mmol) was added with stirring and the mixture was heated to reflux for about 5 h (checked by TLC).

Reference： [1]Tang, Zi-Long; Xia, Zan-Wen; Chang, Shu-Hong; Wang, Zhao-Xu [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 16, p. 3378 - 3381]

73
[ 14068-53-2 ]
C₁₃H₈ClF₃N₂O₃ [ No CAS ]
C₁₇H₁₄F₃N₅O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With pyridine In acetonitrile at 0 - 20℃;

Reference： [1]He, Lei-En; Wu, Ying-Ying; Zhang, Han-Yun; Liu, Man-Yun; Shi, De-Qing [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 5, p. 1308 - 1313]

74
[ 14068-53-2 ]
C₁₃H₇ClF₄N₂O₃ [ No CAS ]
C₁₇H₁₃F₄N₅O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With pyridine In acetonitrile at 0 - 20℃;

Reference： [1]He, Lei-En; Wu, Ying-Ying; Zhang, Han-Yun; Liu, Man-Yun; Shi, De-Qing [Journal of Heterocyclic Chemistry, 2015, vol. 52, # 5, p. 1308 - 1313]

75
[ 14068-53-2 ]
[ 14529-54-5 ]
5-bromo-3-((5-ethyl-1,3,4-thiadiazol-2-yl)amino)-1-methylpyridin-2(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 100℃; for 2h; Inert atmosphere;	332a Example 332a 5-Bromo-3-(5-ethyl-1,3,4-thiadiazol-2-ylamino)-1-methylpyridin-2(1H)-one 332a Example 332a 5-Bromo-3-(5-ethyl-1,3,4-thiadiazol-2-ylamino)-1-methylpyridin-2(1H)-one 332a A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 5-ethyl-1,3,4-thiadiazol-2-amine (500 mg, 3.88 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (1.55 g, 5.81 mmol), Pd2(dba)3 (357 mg, 0.39 mmol), XantPhos (451 mg, 0.78 mmol), Cs2CO3 (2.5 g, 7.67 mmol), and 1,4-dioxane (40 mL). The system was subjected to three cycles of vacuum/nitrogen flush and heated at 100°C for 2 h. The mixture was cooled to 90°C and filtered. The filtrate was cooled in an ice-water bath and then filtered again to afford 332a (574 mg, 47%) as a white solid. MS-ESI: [M+H]+ 315.1

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - EP2773638, 2015, B1 Location in patent: Paragraph 1370; 1371

76
[ 14068-53-2 ]
[ 1254781-51-5 ]
N-(5-ethyl-1,3,4-thiadiazol-2-yl)-N'-(4-methyl-1,2,3-thiadiazole-5-ylformyll)urea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
24%	In 1,2-dichloro-ethane at 20℃; for 8.25h;	15 Compound GDD-105: N- (5- ethyl-1,3,4-thiadiazol-2-yl)-N'- (4- methyl-1,2,3-thiadiazole-5-ylformyl) urea and structural identification 2.7 mmol of 2-amino-5-ethyl-1,3,4-thiadiazole and 20 ml 1, 2-dichloroethane in 100 ml round bottom flask and stirred until the 2-amino -5 - ethyl-1,3,4-thiadiazole was completely dissolved, was added dropwise with stirring 3 mmol of4-methyl - 1,2,3-thiadiazole-5-formylphenyl isocyanate, 15 minutes the addition wascomplete, immediately precipitate, was stirred at room temperature for 8 hours. aftercompletion of the reaction, allowed to stand, the solid product was suction filtered,and the filtrate solvent was removed by rotary evaporation, ethyl acetate with volumeratio of 1:3: petroleum ether and recrystallized in a refrigerator to precipitate asolid, the solid product was combined with a volume of ethyl acetate 1:3: dried productwas washed with petroleum ether; mp: 182-184 ° C, yield 24%;

Reference： [1]Current Patent Assignee: NANKAI UNIVERSITY; LIER CHEMICAL COMPANY LIMITED - CN102225918, 2016, B Location in patent: Paragraph 0083-0085

77
[ 14068-53-2 ]
[ 50-00-0 ]
[ 92-84-2 ]
2-(phenothiazin-N-yl-methyl)amino-5-ethyl-1,3,4-thiadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	In ethanol at 20℃; for 6h;	3 Example 3 To a dry three-necked flask 0.001mol phenothiazine, 0.003mol mass concentration37% to 40% formaldehyde solution (manufacturer: Tianjin Baishi Chemical Co., Ltd.) and 0.002mol2-amino-5-ethyl-1,3,4-thiadiazole, was added 11mL mass fraction of 95% ethanol, at roomThe reaction was stirred for 6 hours at the temperature, this time, TLC monitoring point to the starting material disappeared phenothiazine, a reaction solution;Wherein, TLC developing solvent is a mixture of ethyl acetate and petroleum ether made, and ethyl acetate and petroleumEther volume ratio of 1: 5;2) The reaction mixture solvent was distilled off, the residue is the three-necked flask crude, the crude product was dried over anhydrousRecrystallized from ethanol to obtain a white powder of 2-ethyl--5- (N- phenothiazine-methyl) amino-1,3,4-thiadiazoleOxazole, yield 80%

Reference： [1]Current Patent Assignee: SHAANXI UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN103288816, 2016, B Location in patent: Paragraph 0046; 0047; 0048; 0049; 0050

78
[ 14068-53-2 ]
[ 4635-59-0 ]
4-chloro-N-(5-ethyl-1,3,4-thiadiazol-2-yl)butanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium carbonate In toluene at 20℃; for 4h;	3 General procedure for the preparation of 4-Chloro-N-(5-substituted-1,3,4-thiadiazol-2-yl)butanamide (23-29) General procedure: A mixture of 5-substituted-1,3,4-thiadiazol-2-amine (16-22,0.04 mol), 4-chloro-butyryl chloride (11.3 g, 9.0 ml, 0.08 mol) and potassium carbonate (5.5 g, 0.04 mol) in toluene (100 ml) wasstirred at room temperature for 4 h. The toluene was then evaporatedunder reduced pressure. The residuewas then quenched with water, stirred, and filtered then purified by silica gel and neutralalumina chromatography. The obtained solid was washed, driedand recrystallized to give the required products 23-29 (Table 1).

Reference： [1]El-Subbagh, Hussein I.; Hassan, Ghada S.; El-Taher, Kamal E.H.; El-Messery, Shahenda M.; El-Azab, Adel S.; Abdelaziz, Alaa A.-M.; Hefnawy, Mohamed M. [European Journal of Medicinal Chemistry, 2016, vol. 124, p. 237 - 247]

79
[ 14068-53-2 ]
1-(7-(benzyloxy)-5-methoxybenzo[d]thiazol-2-yl)-2-bromoethanone [ No CAS ]
7-(benzyloxy)-2-(2-ethylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-5-methoxybenzo[d]thiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.425 g	In isopropyl alcohol at 85 - 155℃; for 4.75h; Sealed tube; Microwave irradiation;	30 Example 30: 7-(Benzyloxy)-2-(2-ethylimidazo[2,l-b][l,3,4]thiadiazol-6-yl)-5- methoxybenzo[d]thiazole A sealable vessel was charged with 5-ethyl-l,3,4-thiadiazol-2-amine (1.08 g, 8.36 mmol), l-(7-(benzyloxy)-5-methoxybenzo[d]thiazol-2-yl)-2-bromoethanone (Intermediate ID, 1.64 g, 4.18 mmol) and isopropanol (25 mL). The reaction mixture was heated at 85 °C for 4 h, after which it was transferred to a micro waveable vessel and heated at 155 °C for 45 min. The cooled reaction mixture was then concentrated and the concentrate was partitioned with ethyl acetate-saturated aqueous sodium bicarbonate. The organic phase was separated, dried (MgS04), filtered and concentrated to dryness. The residue was purified by ISCO (EtOAc-DCM) to give 7-(benzyloxy)-2-(2-ethylimidazo[2,l- b][l,3,4]thiadiazol-6-yl)-5-methoxybenzo[d]thiazole (0.425 g, 1.01 mmol, 24%) as a beige solid. LC (Method B): 2.379 min. HRMS (ESI): calcd for C2iHi9N402S2 [M+H]+ m/z 423.0871, found 423.0901. 1HNMR (400 MHz, DMSO-d6) δ ppm 8.83 (s, 1H), 7.50 (m, 2H), 7.42 (m, 2H), 7.35 (m, 1H), 7.16 (d, J = 2.0 Hz, 1H), 6.76 (d, J = 2.0 Hz, 1H), 5.34 (s, 2H), 3.84 (s, 3H), 3.12 (q, 7 = 7.4 Hz, 2H), 1.36 (t, J = 7.6 Hz, 3H).

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2016/138199, 2016, A1 Location in patent: Paragraph 0084

80
[ 14068-53-2 ]
2-bromo-1-(ferrocen-1-yl)ethan-1-one [ No CAS ]
2-ethyl-6-ferrocenylimidazolo[2,1-b]-1,3,4-thiadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	In ethanol for 0.2h; Microwave irradiation;	General procedure for microwave-assistedcatalyst-free synthesis of ferrocenyl imidazolo[2,1-b]-1,3,4-thiadiazoles 3 General procedure: 2-Amino-5-substituted-1,3,4-thiadiazole (1 mmol), α-bromoacetyl ferrocene (1 mmol), and ethanol (5 mL) were mixed uniformly in a dry crucible and then subjected tomicrowave irradiation of 700 W for 30 s. The crucible was removed from the microwave, ethanol (5 mL) was added,and then subjected to microwave irradiation; this processwas repeated for 20-25 times until the reaction was complete(monitored by TLC). Then, the reaction was allowedto cool to room temperature. Water of 10 mL was addedand the mixture was neutralized to pH 7-8 with saturatedsodium carbonate solution. The obtained solid was filtered,washed with water, and dried. The crude productwas recrystallized in dimetyl formamide (DMF) to afford3a-m.
56.4%	In ethanol for 0.2h; Microwave irradiation;	1.2; 1.3; 1.4; 1.5; 1.6; 1.7 (2), 2-amino-5-ethyl-1,3,4-thiadiazole, α-bromo-acetylferrocene and ethanol were stirredWherein the molar ratio of 2-amino-5-ethyl-1,3,4-thiadiazole and α-bromo-acetylferrocene is 1: 3;(3), the mixture was placed in a microwave oven, the power control at 700W, turn on the microwave radiation for 30 seconds ;;(4) After the reaction of α-bromo-acetyl ferrocene is completed, microwave reaction is carried out for 12 minutes;(5), adding water to the reaction solution, and then adjusting the pH of the reaction solution to 7 to 8 with saturated sodium carbonate solution;(6), suction filtration, washed with water filter cake, dried to give the crude product;(7), recrystallized from DMF to give a brown powder.Elemental analysis confirmed that the product was 2-ethyl-6-ferrocenyl-imidazo [2,1-b] -1,3,4-thiadiazole,The yield was 56.4%.
25%	In methanol for 10h; Reflux;	2 Embodiment 2: 1) to the drying with stirring and reflux condenser of the three-port flask by adding α-bromo-acetyl ferrocene (0.61g, 0 . 002mol), 2-amino-5-ethyl -1, 3, 4-thiadiazole (0.26g, 0 . 002mol) and 10 ml methanol, the α-bromo-acetyl ferrocene, 5-substituted-2-amino -1, 3, 4-thiadiazole in dissolved in methanol, get mixed solution A; wherein 5-substituted-2-amino hydrogen, C1-C3 straight chain alkyl, methyl, vinyl, phenyl, substituted phenyl or 4-pyridyl; 2) stir, A the mixed solution is heated to reflux temperature, reflux reaction in the water bath 10 hours, accompanied by TLC detection; 3) after the reaction, detected by TLC the reaction solution after the end of the natural cooling to room temperature, sodium carbonate is added to the solution pH of the solution is adjusted to value 7-8, B to obtain the mixed solution; 4) distilled B solvent of the mixed solution, the remaining product water washing, filtering, drying, DMF is recrystallized to get 2-ethyl-6-ferrocenyl-imidazo [2,1-b] - 1, 3, 4-thiadiazole 0.17g, yield 25%,

Reference： [1]Liu, Yuting; Yang, Lan; Yin, Dawei [Journal of Chemical Research, 2021, vol. 45, # 5-6, p. 422 - 427]
[2]Current Patent Assignee: ZHANGJIAGANG MAOAN TRADE - CN107501343, 2017, A Location in patent: Paragraph 0028; 0029; 0030-0034; 0038-0044
[3]Current Patent Assignee: SHAANXI UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN104098609, 2016, B Location in patent: Paragraph 0052-0056

81
[ 14068-53-2 ]
[ 1483-97-2 ]
C₂₆H₂₇N₇S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89.6%	With choline chloride; oxalic acid at 70℃;	9 Example 9 Preparation of 3,6-diacetyl-9-ethylcarbazole 2-amino-5-ethyl-1,3,4-thiadiazole Schiff base Add 2 g (0.014 mol) of choline chloride, 1.26 g (0.014 mol) of oxalic acid to a dry three-necked flask,Stir at 70 ° C to obtain a colorless and transparent solution, namely a eutectic solvent, cool to room temperature, and add 670.4 mg (2.4 mmol) of 3,6-diacetyl-9-ethylcarbazole.686.0 mg (5.04 mmol) of 2-amino-5-ethyl-1,3,4-thiadiazole was reacted at 70 ° C and monitored by TLC until the reaction was complete.After the reaction, a small amount of water was added to the reaction flask to precipitate a solid, which was filtered by suction, the filter cake was washed with water, dried, and recrystallized.Thus, 3,6-diacetyl-9-ethylcarbazole 2-amino-5-ethyl-1,3,4-thiadiazole Schiff base was obtained. The water phase can be recovered to recover the eutectic solvent. Yield 89.6%,
83.1%	With toluene-4-sulfonic acid at 20℃; for 0.25h;	4 Example 4 1) To a dry mortar was added 0.005 mol of 3,6-diacetyl-9-ethylcarbazole, 0.011 mol2-amino-5-ethyl-1,3,4-thiadiazole and 0.011 mol of p-toluenesulfonic acid were ground at room temperature for 15 min. TLC monitoring showed 3,6- The starting point of the acetyl-9-ethylcarbazole and 2-amino-5-ethyl-1,3,4-thiadiazole disappears, indicating that the raw material is completely reacted And then allowed to stand for 30 min to obtain a mixture; wherein the developing agent is a mixed solvent of ethyl acetate and petroleum ether in a volume ratio of 1: 3;2) The mixture was washed with water to obtain 3,6-diacetyl-9-ethylcarbazole 2-amino-5-ethyl-1, 3,4-thiadiazole Schiff base. M.p .: 147.6-148.3 ° C in a yield of 83.1%.

Reference： [1]Current Patent Assignee: SHAANXI UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN110627783, 2019, A Location in patent: Paragraph 0075-0079
[2]Current Patent Assignee: SHAANXI UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN106432220, 2017, A Location in patent: Paragraph 0048; 0049; 0050; 0051; 0052; 0053

82
[ 14068-53-2 ]
2-amino-5-[2-(4-bromophenyl)ethyl]-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one [ No CAS ]
[ 61117-58-6 ]
4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]-N-(5-ethyl-1,3,4-thiadiazol-2-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene at 90℃; for 5h; Autoclave;	Synthesis of7a-l; general procedure General procedure: To a suspension of 6(0.1 mol) in 1,4-dioxane (5 mL), amine nucleophiles R(a-l) (0.2 mol), Pd(OAc)2(5 mol%) and Xantphos (5 mol%) were added in an autoclave at about 25 °C. To this, Co2(CO)8(0.25 mol for primary and secondary amine nucleophiles, 0.7 mol for aryl amine nucleophiles) was added and the resultant reaction mixture was heated to about 90 °C for 5 h in the autoclave. On reaction completion, the reaction mixture was quenched using water and the solid obtained was stirred for 30 min and collected by filtration. The crude material was further purified by hot methanol to afford the desired benzamides 7a-l.

Reference： [1]Selvakumar, Balaraman; Elango, Kuppanagounder P. [Journal of Chemical Research, 2017, vol. 41, # 4, p. 230 - 234]

83
[ 14068-53-2 ]
[ 188724-74-5 ]
4-benzoyl-N-(5-ethyl-1,3,4-thiadiazol-2-yl)-1,5-diphenyl-1H-pyrazole-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	In acetonitrile Reflux;	General procedure for the synthesis of compound 4 derivatives General procedure: To a stirred solution of compound (2) or (6) in acetonitrile (10 mL) was added the solution of 2-amino-1,3,4-thidiazolederivatives (3) in acetonitrile (5 mL) dropwise.The mixture wasreuxed for 4-5 h. Later, the solvent was evaporated underreduced pressure to give an oily residue which was trituratedwith anhydrous diethylether and fnally recrystallized from theindicated solvents.

Reference： [1]Saçmacı, Mustafa; Arslaner, Çiler; Şahin, Ertan [Phosphorus, Sulfur and Silicon and the Related Elements, 2017, vol. 192, # 10, p. 1134 - 1139]

84
[ 14068-53-2 ]
[ 957470-78-9 ]
ethyl-3-[(5-ethyl-1,3,4-thiadiazol-2-yl)-amino]-carbonyl}-1,5-diphenyl-1H-pyrazole-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	In acetonitrile Reflux;	General procedure for the synthesis of compound 4 derivatives General procedure: To a stirred solution of compound (2) or (6) in acetonitrile (10 mL) was added the solution of 2-amino-1,3,4-thidiazolederivatives (3) in acetonitrile (5 mL) dropwise.The mixture wasreuxed for 4-5 h. Later, the solvent was evaporated underreduced pressure to give an oily residue which was trituratedwith anhydrous diethylether and fnally recrystallized from theindicated solvents.

Reference： [1]Saçmacı, Mustafa; Arslaner, Çiler; Şahin, Ertan [Phosphorus, Sulfur and Silicon and the Related Elements, 2017, vol. 192, # 10, p. 1134 - 1139]

85
[ 14068-53-2 ]
[ 1262234-20-7 ]
N,N'-bis(5-ethyl-1,3,4-thiadiazol-2-yl)-1,5-di-phenyl-1Hpyrazole-3,4-dicarboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	In acetonitrile for 5h; Reflux;	General procedure for the synthesis of compound 7 derivatives General procedure: A mixture of pyrazole carboxylic acid dichloride (6) (1.0 mmol),and the appropriate 2-amino-1,3,4-thiadiazole derivatives 3(4.0 mmol) was heated under reux condition in freshly distilled acetonitrile (25 mL) for 5 h. The solvent was evaporatedin vacuo and residue was washed with water. The precipitatedcrude product was fltered and crystallized from the appropriatesolvent.

Reference： [1]Saçmacı, Mustafa; Arslaner, Çiler; Şahin, Ertan [Phosphorus, Sulfur and Silicon and the Related Elements, 2017, vol. 192, # 10, p. 1134 - 1139]

86
[ 14068-53-2 ]
[ 104-88-1 ]
C₁₁H₁₀ClN₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In toluene at 120℃; Molecular sieve; Sealed tube;
	In toluene at 120℃; Molecular sieve; Sealed tube;	4.1.1. Typical experimental procedure for ethers 1-7, 11-20 General procedure: A screw-capped V-shaped vial (2.0 mL) was charged with 2-aminothiazole (0.36 mmol, 1.0 equiv), aldehyde (0.40 mmol, 1.1equiv), freshly activated 4 Å molecular sieves (300 mg) and dry toluene(1.5 mL). The vial was capped with a pressure cap and stored at 120 °C for 14-24 h until complete consumption of 2-aminothiazole (monitoredby 1H NMR). The resulting mixture containing imine was cooled to room temperature and the solvent was removed under reduced pressure. Under inert atmosphere, the residue was redissolved in dry toluene(1 mL) and then CuOTf*C6H6 (18 mg, 0.036 mmol, 10 mol %), Cu(OTf)2 (13 mg, 0.036 mmol, 10 mol %), alkyne (0.72 mmol, 2 equiv) and 4 Å molecular sieves (100 mg) were added. The reaction mixture was additionally stirred in the vial capped with a pressure cap at 120 °C for 2 h. After the completion of the reaction, the mixture was filtered through a plug of neutral aluminum oxide (eluent - EtOAc). The filtrate was concentrated under reduced pressure to give a crude material,which was purified by column chromatography on silica gel (eluentEt3N:EtOAc/petroleum ether) or neutral aluminum oxide (eluent EtOAc/petroleum ether) to give product.

Reference： [1]Rassokhina, Irina V.; Tikhonova, Tatyana A.; Kobylskoy, Sergey G.; Babkin, Igor Yu.; Shirinian, Valerii Z.; Gevorgyan, Vladimir; Zavarzin, Igor V.; Volkova, Yulia A. [Journal of Organic Chemistry, 2017, vol. 82, # 18, p. 9682 - 9692]
[2]Tikhonova, Tatyana A.; Rassokhina, Irina V.; Kondrakhin, Eugeny A.; Fedosov, Mikhail A.; Bukanova, Julia V.; Rossokhin, Alexey V.; Sharonova, Irina N.; Kovalev, Georgy I.; Zavarzin, Igor V.; Volkova, Yulia A. [Bioorganic Chemistry, 2020, vol. 94]

87
[ 14068-53-2 ]
2-(2,3-dimethylphenylamino)benzoic anhydride [ No CAS ]
2-(2,3-dimethylphenylamino)-N-(5-ethyl[1,3,4]thiadiazol-2-yl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With acetic acid; zinc In 1,4-dioxane for 2.5h; Reflux;	General procedure for the synthesis of (I-III) General procedure: Compound (A) (6.35 mmol), appropriatethiadiazole (6.35 mmol), zinc dust (0.006 g), glacial acetic acid (0.61 mL, 10.67 mmol) and dioxane (40 mL) were placed in 100 mL rounded bottomed flask, fixed with reflux condenser,boiling stone were added. The reaction mixture was refluxed for about 2.5 h with continuouslystirring, and the reaction was checked by TLC to make sure that completion of reaction. Thesolvent was evaporated under vacuum, and residue was dissolved in ethyl acetate, then thereaction mixture was washed, with NaHCO3 (10%) 3 times, HCl (1 M) 3 times, and 3 times with distilled water, using (20 mL), filtered over anhydrous sodium sulfate. The filtrate wasevaporated and the residue was re-dissolved in ethyl acetate and filtered. The re-crystallization was carried out by adding petroleum ether (60-80 oC) on the filtrate until turbidity occurred andkept in cold place over night. Then the mixture was filtered while it is cold and the crystals werecollected to produce compound (I-III).

Reference： [1]Ahmadi, Abbas [Bulletin of the Chemical Society of Ethiopia, 2017, vol. 31, # 1, p. 171 - 175]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	14068-53-2	MDL No. :	MFCD00003111
Formula :	C₄H₇N₃S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QXTRPGAMVIONMK-UHFFFAOYSA-N
M.W :	129.18	Pubchem ID :	26444
Synonyms :

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

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

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

[ CAS No. 14068-53-2 ] {[proInfo.proName]}

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[ 14068-53-2 ] Synthesis Path-Downstream 1~87

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[ 14068-53-2 ]

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[ 14068-53-2 ]

Thiadiazoles

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[ CAS No. 14068-53-2 ] {[proInfo.proName]}

Quality Control of [ 14068-53-2 ]

Related Doc. of [ 14068-53-2 ]

Product Details of [ 14068-53-2 ]

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Application In Synthesis of [ 14068-53-2 ]

[ 14068-53-2 ] Synthesis Path-Downstream 1~87

Related Functional Groups of [ 14068-53-2 ]

Amines

Related Parent Nucleus of [ 14068-53-2 ]

Thiadiazoles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

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Inquiry

Related Functional Groups of
[ 14068-53-2 ]

Related Parent Nucleus of
[ 14068-53-2 ]