Name: 50868-68-3|(E)-3-(5-Bromothiophen-2-yl)acrylic acid|97%
Brand: Ambeed
SKU: A392441
Rating: 98 (32 reviews)

1
[ 151451-43-3 ]
[ 50868-68-3 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide
	With water; sodium hydroxide In tetrahydrofuran; methanol at 20℃;	5.1.22. (E)-3-(5-Bromothiophen-2-yl)acryloyl azide (17a) General procedure: A mixture of ethyl (E)-3-(5-bromothiophen-2-yl)acrylate (16a) (6.34g, 24.3 mmol) and 1 M NaOH aq. (48.6 mL, 48.6 mmol) in THF (20 mL) and MeOH (20 mL) was stirred at rt overnight. The mixture wasneutralized with 1 M HCl aq. and the solution was extracted with EtOAc.The organic layer was separated, washed with brine, dried over Na2SO4and concentrated in vacuo. This residue was used to the next reactionwithout further purification. Ethyl chloroformate (3.49 mL, 36.5 mmol)was added to a mixture of the crude product, TEA (5.09 mL, 36.5 mmol)in acetone (48 mL) at 0 C. After stirring at this temperature for 1 h, amixture of sodium azide (2.52 g, 38.8 mmol) in water (9.5 mL) wasadded dropwise to the reaction mixture. The mixture was stirred at 0 Cfor 1 h. The resulting mixture was poured into water and stirred at rt for10 min. The precipitate was collected by filteration to give the titlecompound as a pale pink solid (4.62 g, 17.9 mmol, 78%). 1H NMR (300MHz, CDCl3) δ 6.10 (1H, d, J = 15.4 Hz), 6.98-7.12 (2H, m), 7.59-7.86(1H, m).

Reference： [1]Miller; Nord [Journal of Organic Chemistry, 1950, vol. 15, p. 89,93]
[2]Sakurai, Fumie; Yukawa, Takafumi; Kina, Asato; Murakami, Masataka; Takami, Kazuaki; Morimoto, Sachie; Seto, Masaki; Kamata, Makoto; Yamashita, Tohru; Nakashima, Kosuke; Narita, Naohiro; Bettini, Ezio; Ugolini, Annarosa; Corsi, Mauro; Hasui, Tomoaki [Bioorganic and Medicinal Chemistry, 2022, vol. 56]

2
[ 4701-17-1 ]
[ 141-82-2 ]
[ 50868-68-3 ]

Yield	Reaction Conditions	Operation in experiment
94%	With piperidine; pyridine for 3h; Reflux; Inert atmosphere;
94%	With piperidine; pyridine for 3h; Reflux;	(E)-3-(5-Bromothiophen-2-yl)acrylic acid (5). To a solution of 5-bromothiophene- 2-carboxaldehyde (4) (10.15 g, 51.53 mmol) in pyridine (128 mL) were added malonic acid (16.25 g, 154.6 mmol) and piperidine (2.57 mL, 25.76 mmol). The reaction mixture was heated at reflux for 3 h, cooled to room temperature and concentrated to give a dark oil. The oil was diluted with TbO (30 mL), at which time a solid precipitated. The suspension was then acidified to pH 2 with 6 M HC1. The precipitate was filtered and washed with H2O (3 x 15 mL). The filter cake was dissolved in EtOAc, dried (MgSCL), filtered, and concentrated to give 5 (11.29 g, 94%) as a tan solid: NMR (300 MHz, DMSO-de) d 12.41 (brs, 1 H), 7.66 (d, J= 15.9 Hz, 1 H), 7.35 (d, J= 3.9 Hz, 1 H), 7.27 (d, J= 3.9 Hz, 1 H), 6.15 (d, J= 15.9 Hz, 1 H). Spectral data are consistent with literature properties.37
90.5%	Stage #1: 5-bromo-2-thiophencarboxaldehyde; malonic acid With piperidine; pyridine at 80℃; for 1h; Stage #2: at 100℃; for 12h; Stage #3: With hydrogenchloride	INTERMEDIATE 47 [ (2E)-3- (5-BROMOTHIEN-2-YL) ACRYLIC ACID] INTERMEDIATE 47 [ (2E)-3- (5-BROMOTHIEN-2-YL) ACRYLIC ACID] Malonic acid (44.40 g, 426.7 mmol) was added to a mixture [OF 5-BROMOTHIOPHENE-2-] carbaldehyde (50 g, 261.7 mmol), piperidine (2.84 mL) and pyridine (150 mL). The mixture was refluxed for 1 h at [80°C] and than at [100 °C] over night. The volatiles were evaporated and the residue was dissolved in water and acidified with hydrochloric acid (pH 2). The crude product was crystallized in ethanol. Yield: 55.24 g (90.5 %). 1H NMR (270 MHz, CH30H-d4) 8 ppm 6.14 (d, [J=15.] 83 Hz, 1 H) 7.11-7. 16 [(M,] 2 H) 7.68 (d, J=16. 36 Hz, 1 H); MS 233.1 [(M-H) +] ; Purity (HPLC) [94 %.]

72%	With piperidine In pyridine for 2h; Reflux;	General procedure for the synthesis of the 3-(5-bromo-2-thienyl)acrylic acid 4 and 3-(5-phenyl-2-thienyl)acrylic 5 via Knoevenagel condensation General procedure: 2-Thiophenecarboxyaldehyde derivative (1 eq, 30 mmol) was dissolved in pyridine (60 mL) and piperidine (3 mL). After addition of malonic acid (1.2 eq, 36 mmol), the mixture was refluxed for 2 h. After cooling, the mixture was poured into a mixture of 200 mL water, 200 mL ice and 200 mL concentrated hydrochloric acid to yield a solid. The precipitating solid was filtered off, washed with water and dried under pressure to give the corresponding 3-(2-thienyl)acrylic acid derivative.; 4.1.1.1 3-(5-bromo-2-thienyl)acrylic acid 4 (0023) 1H NMR (DMSO-d6, 250MHz): δ=12.46 (bs, 1H), 7.67 (d, J=15.7Hz, 1H), 7.36 (d, J=3.9Hz, 1H), 7.28 (d, J=3.9Hz, 1H), 6.16 (d, J=15.8Hz, 1H); 13C NMR (DMSO-d6, 62MHz): δ=167.53, 141.25, 136.28, 132.85, 132.28, 118.74, 115.42; LC/MS (ESI): 230.87 [M-H]- and isotopic peak 232.88; HRMS (FAB) cald for C7H4O2SBr (M+H)+ 230.9115, found 230.9131; purity>99%; beige powder. Yield=72%.
70%	With piperidine; pyridine for 5h; Inert atmosphere; Reflux;	(E)-3-(5-Bromothiophen-2-yl)acrylic acid (SI-2). To a solution of 5-bromothiophene-2-carboxaldehyde (SI-1,32.9 g, 172 mmol) in pyridine (430 mL), malonic acid (54.3 g, 516 mmol) and piperidine (8.6 mL, 86.1 mmol) wasadded. The reaction mixture was heated at reflux for 5 h, cooled to room temperature, and concentrated to give adark oil. The oil was diluted with H2O (500 mL), and a solid precipitate was formed. The suspension was acidifiedto pH 2 with 6 M HCl. The precipitate was filtered and washed with H2O (3 x 50 mL). The filter cake was triturated with EtOAc, and the resulting solid was washed with EtOAc (3 X 50 mL) to give a tan solid (~25 g) that wasdissolved in hot acetone (~700 mL) and filtered through a pad of SiO2. The filtrate was partially concentrated andfiltered. This process was repeated to give an off-white solid (20.5 g). The retained aqueous filtrate wassubsequently reextracted with EtOAc (3 X 100 mL), and the combined organic extracts were washed withsaturated aqueous NaCl, dried (MgSO4), filtered, and added to the EtOAc trituration washings. The dark solutionwas concentrated to give a black residue that was dissolved in hot acetone, filtered through a plug of SiO2, andconcentrated. Trituration of the residue with EtOAc and recrystallization of the resulting solid in acetone gaveadditional off-white solid SI-2 (28.0 g total, 70%): 1H NMR (300 MHz, DMSO-d6): δ 12.46 (brs, 1 H), 7.66 (d, J =15.6 Hz, 1 H), 7.35 (d, J = 3.6 Hz, 1 H), 7.27 (d, J = 4.0 Hz, 1 H), 6.15 (d, J = 16.0 Hz, 1 H). Spectral propertieswere consistent with literature data.1
	Stage #1: 5-bromo-2-thiophencarboxaldehyde; malonic acid With piperidine; pyridine for 6h; Heating / reflux; Stage #2: With hydrogenchloride In water at 0℃;	2.a Example 2 3-[5-(4-Chloro-phenyl)-thiophen-2-yl]-1-(piperidin-1-yl)-propenone [Show Image] (a) 3-(5-Bromo-thiophen-2-yl)-acrylic acid 3 g (15.7 mmol) of 5-bromo-thiophene-2-carbaldehyde were dissolved in 30 ml of pyridine and 1.96 g (18.8 mmol) of malonic acid and 133 mg (1.6 mmol) of piperidine was added. The reaction mixture was boiled under reflux for 6 h. After cooling to room temperature, it was poured into a mixture of ice and concentrated aqueous hydrochloric acid whereupon the product precipitated. The product was isolated by filtration, dissolved in ethyl acetate, and the solution was washed with 0.1 M hydrochloric acid. The organic phase was dried with sodium sulfate, filtered and the solvent was removed under reduced pressure. Yield: 3.0 g. MS: m/e = 234 (M+H)+
	With piperidine In dimethyl sulfoxide at 100℃; for 16h;

Reference： [1]Tasker, Nikhil R.; Rastelli, Ettore J.; Blanco, Isabella K.; Burnett, James C.; Sharlow, Elizabeth R.; Lazo, John S.; Wipf, Peter [Organic and Biomolecular Chemistry, 2019, vol. 17, # 9, p. 2448 - 2466]
[2]Current Patent Assignee: COMMONWEALTH SYSTEM OF HIGHER EDUCATION - WO2020/102245, 2020, A1 Location in patent: Paragraph 0084; 0098
[3]Current Patent Assignee: BENEVOLENTAI LIMITED - WO2004/828, 2003, A1
[4]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]
[5]Rastelli, Ettore J.; Sannino, Sara; Hart, Duncan J.; Sharlow, Elizabeth R.; Lazo, John S.; Brodsky, Jeffrey L.; Wipf, Peter [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 46]
[6]Current Patent Assignee: SANOFI - EP1939180, 2008, A1 Location in patent: Page/Page column 29
[7]Ahmed, Syed T.; Parmeggiani, Fabio; Weise, Nicholas J.; Flitsch, Sabine L.; Turner, Nicholas J. [Organic Letters, 2016, vol. 18, # 21, p. 5468 - 5471]

3
[ 50868-68-3 ]
[ 636999-00-3 ]

Yield	Reaction Conditions	Operation in experiment
83.4%	Stage #1: (E)-3-(5-bromo-2-thienyl)-2-propenoic acid With thionyl chloride In chloroform at 75℃; for 2h; Stage #2: With 1,4-dioxane; sodium azide; water at 0℃; for 0.166667h;	INTERMEDIATE 48 [(2E)-3- (5-BROMOTHIEN-2-YL)] acryloyl azide INTERMEDIATE 48 [(2E)-3- (5-BROMOTHIEN-2-YL)] acryloyl azide Thionyl chloride (1.04 mL) was added to a solution of [(2E)-3- (5-BROMOTHIEN-2-YL)] acrylic acid (1.04 g, 4.46 mmol) in chloroform (20 mL) and the mixture was refluxed for 2h at [75°C] and than used in the next step. The above solution was added drop wise to a stirred suspension of sodium azide (0.58 g, 8.93 mmol), dioxane (3 mL) and water (3 mL) in an ice bath. After 10 min a precipitate appeared which was filtered off and washed with water. The residue was dissolved in dichloromethane, dried with MgS04, filtered and the solvent was removed to afford: 0.96 g (83.4 [%).'H] NMR (270 MHz [CH30H-D4)] 8 ppm 6.20 (d, [J=15.] 57 Hz, 1 H) 7.15-7. 25 (m, 2 H) 7.80 (d, [J=15.] 57 Hz, 1 H); MS 258.1 [(M-H)] [+ ;] Purity (HPLC) 65 %.
	Stage #1: (E)-3-(5-bromo-2-thienyl)-2-propenoic acid With chloroformic acid ethyl ester; triethylamine In acetone at 0℃; for 1.5h; Inert atmosphere; Stage #2: With sodium azide In water; acetone at 0℃; Inert atmosphere;
4.62 g	Stage #1: (E)-3-(5-bromo-2-thienyl)-2-propenoic acid With chloroformic acid ethyl ester; triethylamine In acetone at 0 - 20℃; for 1h; Stage #2: With sodium azide In water; acetone at 0℃; for 1h;	5.1.22. (E)-3-(5-Bromothiophen-2-yl)acryloyl azide (17a) General procedure: A mixture of ethyl (E)-3-(5-bromothiophen-2-yl)acrylate (16a) (6.34g, 24.3 mmol) and 1 M NaOH aq. (48.6 mL, 48.6 mmol) in THF (20 mL) and MeOH (20 mL) was stirred at rt overnight. The mixture wasneutralized with 1 M HCl aq. and the solution was extracted with EtOAc.The organic layer was separated, washed with brine, dried over Na2SO4and concentrated in vacuo. This residue was used to the next reactionwithout further purification. Ethyl chloroformate (3.49 mL, 36.5 mmol)was added to a mixture of the crude product, TEA (5.09 mL, 36.5 mmol)in acetone (48 mL) at 0 C. After stirring at this temperature for 1 h, amixture of sodium azide (2.52 g, 38.8 mmol) in water (9.5 mL) wasadded dropwise to the reaction mixture. The mixture was stirred at 0 Cfor 1 h. The resulting mixture was poured into water and stirred at rt for10 min. The precipitate was collected by filteration to give the titlecompound as a pale pink solid (4.62 g, 17.9 mmol, 78%). 1H NMR (300MHz, CDCl3) δ 6.10 (1H, d, J = 15.4 Hz), 6.98-7.12 (2H, m), 7.59-7.86(1H, m).

Reference： [1]Current Patent Assignee: BENEVOLENTAI LIMITED - WO2004/828, 2003, A1
[2]Tasker, Nikhil R.; Rastelli, Ettore J.; Blanco, Isabella K.; Burnett, James C.; Sharlow, Elizabeth R.; Lazo, John S.; Wipf, Peter [Organic and Biomolecular Chemistry, 2019, vol. 17, # 9, p. 2448 - 2466]
[3]Sakurai, Fumie; Yukawa, Takafumi; Kina, Asato; Murakami, Masataka; Takami, Kazuaki; Morimoto, Sachie; Seto, Masaki; Kamata, Makoto; Yamashita, Tohru; Nakashima, Kosuke; Narita, Naohiro; Bettini, Ezio; Ugolini, Annarosa; Corsi, Mauro; Hasui, Tomoaki [Bioorganic and Medicinal Chemistry, 2022, vol. 56]

4
[ 110-89-4 ]
[ 50868-68-3 ]
(E)-3-(5-bromo-thiophen-2-yl)-1-(piperidin-1-yl)-propenone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: (E)-3-(5-bromo-2-thienyl)-2-propenoic acid With N-ethylmorpholine;; O-<[cyano(ethoxycarbonyl)methylene]amino>-1,1,3,3-tetramethyluronium tetrafluoroborate In N,N-dimethyl-formamide at 20℃; for 0.25h; Stage #2: piperidine In N,N-dimethyl-formamide at 20℃; for 16h;	3.a Example 3 3-[5-(4-Fluoro-phenyl)-thiophen-2-yl]-1-(piperidin-1-yl)-propenone [Show Image] (a) 3-(5-Bromo-thiophen-2-yl)-1-(piperidin-1-yl)-propenone; 50 g (2.1 mmol) of 3-(5-bromo-thiophen-2-yl)-acrylic acid, 2.47 g (21.5 mmol) of NEM and 774 mg (2.4 mmol) of TOTU were dissolved in 5 ml of DMF and stirred at room temperature for 15 min. 201 mg (0.5 mmol) of piperidine were added, and the reaction mixture was stirred at room temperature for 16 h. The solvent was removed under reduced pressure. The product was purified by silica gel chromatography. Yield: 458 mg. MS: m/e = 300 (M)+

Reference： [1]Current Patent Assignee: SANOFI - EP1939180, 2008, A1 Location in patent: Page/Page column 30

5
[ 1993-03-9 ]
[ 50868-68-3 ]
(E)-3-[5-(2-fluoro-phenyl)-thiophen-2-yl]-acrylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate In 1,2-dimethoxyethane; water at 20 - 95℃; for 20.1667h;	4.a Example 4 3-[5-(2-Fluoro-phenyl)-th iophen-2-yl]-1-(piperidin-1-yl)-propenone [Show Image] (a) 3-[5-(2-Fluoro-phenyl)-thiophen-2-yl]-acrylic acid; 9.38 g (40.2 mmol) of 3-(5-Bromo-thiophen-2-yl)-acrylic acid and 6.97 g (6 mmol) of tetrakis(triphenylphosphine)palladium were dissolved in 50 ml of degassed DME and stirred for 10 min at room temperature. 8.44 g (60.4 mmol) of 2-fluorophenylboronic acid and 50 ml of a 2 M aqueous sodium carbonate solution were added together with an additional 5 ml of degassed DME. The reaction mixture was heated to 95 °C for 4 h, and then stirred at room temperature for 16 h. The product precipitated partially from the reaction solution and was collected by filtration. This solid was boiled for 1 h in ethyl acetate and filtered while hot. The solvent was removed under reduced pressure. The remaining reaction solution was evaporated to dryness. The residue was taken up in ethyl acetate/water and filtered. The organic phase was dried with sodium sulfate, filtered and the solvent was removed under reduced pressure. The combined product was purified by silica gel chromatography. Yield: 7.5 g. MS: m/e = 249 (M+H)+

Reference： [1]Current Patent Assignee: SANOFI - EP1939180, 2008, A1 Location in patent: Page/Page column 30-31

6
[ 1679-18-1 ]
[ 50868-68-3 ]
(E)-3-[5-(4-chloro-phenyl)-thiophen-2-yl]-acrylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate In 1,2-dimethoxyethane; water at 25 - 95℃; for 20.1667h;	2.b (b) 3-[5-(4-Chloro-phenyl)-thiophen-2-yl]-acrylic acid 0.250 g (1.1 mmol) of 3-(5-bromo-thiophen-2-yl)-acrylic acid and 61.9 mg (0.1 mmol) of tetrakis(triphenylphosphine)palladium were dissolved in 5 ml of degassed DME and stirred for 10 min at room temperature. 0.251 g (1.6 mmol) of 4-chlorophenylboronic acid and 1 ml of a 2 M aqueous sodium carbonate solution were added together with an additional 5 ml of degassed DME. The reaction mixture was heated to 95 °C for 4 h, and then stirred at room temperature for 16 h. Solids were removed by filtration and the resulting solution was evaporated to dryness. The residue was dissolved in ethyl acetate and washed three times with a saturated aqueous sodium hydrogencarbonate solution, and once with a saturated sodium chloride solution. The organic phase was dried with sodium sulfate, filtered, and the solvent was removed under reduced pressure. The product was purified by silica gel chromatography. Yield: 0.12 g. MS: m/e = 265 (M+H)+

Reference： [1]Current Patent Assignee: SANOFI - EP1939180, 2008, A1 Location in patent: Page/Page column 29

7
[ 1200575-98-9 ]
[ 50868-68-3 ]
[ 1252613-91-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate In water; acetonitrile at 160℃; for 0.333333h; Irradiation;	INTERMEDIATE A22 (2JE)-3-(5-{2-[l-(tert-Butoxycarbonyl)piperidin-4-yl]-4H-l,3-benzodioxin-6-yl}-2- thienyl)acrylic acid A suspension of tert-butyi 4-[6-(dimethoxyboryl)-4H-l,3-benzodioxin-2-yl]piperidine-l- carboxylate (Intermediate Al 9; 100 mg, 0.255 mmol), (2E)-3-(5-bromo-2-thienyl)acrylic acid (77.4 mg, 0.332 mmol), K2CO3 (88 mg, 0.64 mmol), PdCfcdppf-DCM (22 mg, 0.025 mmol) in MeCNZH2O (4 mL; 2:1) was heated at 160 0C for 20 min in a microwave reactor. The mixture was filtered through a pad of silica and concentrated to give the title compound which was used directly in Example A137 and A138.

Reference： [1]Current Patent Assignee: KANCERA AB - WO2009/150144, 2009, A1 Location in patent: Page/Page column 72

8
[ 50868-68-3 ]
[ 1673-47-8 ]
N'-[(2E)-3-(5-bromothiophene-2-yl)prop-2-enoyl]-3-chlorobenzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate Reflux; Inert atmosphere;	1 General procedure for two steps synthesis of 1,3,4-oxadiazole derivatives 8-17 (Method A) and general procedure for one-step synthesis of 1,3,4-oxadiazole derivatives 8-28 (Method B) General procedure: Method A; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted hydrazide (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (2.5 eq, 50% solution in EtOAc) and triethylamine (3 eq), and the mixture was refluxed under argon atmosphere for 1h-24h. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature, and poured into ice/water. The precipitating solid was filtered off, washed with water, cyclohexan and dried under pressure to give the pure diacylhydrazine derivative. An example of diacylhydrazine derivatives 6-7 synthesis is given below.; 4.1.2.1 N'-[(2E)-3-(5-bromothiophene-2-yl)prop-2-enoyl]-3-chlorobenzohydrazide 6 1H NMR (DMSO-d6, 250 MHz): δ = 10.74 (s, 1H), 10.33 (s, 1H), 8.02 (bs, 1H), 7.95 (d, J = 7.7 Hz, 1H), 7.75 (d, J = 15.6 Hz, 1H), 7.76-7.61 (m, 2H), 7.41 (d, J = 3.9 Hz, 1H), 7.37 (d, J = 3.8 Hz, 1H), 6.52 (d, J = 15.6 Hz, 1H); LC/MS (ESI): 382.84 [M-H]- and isotopic peak: 384.81; purity = 95%. Yield = 59%.; The corresponding diacylhydrazine derivative was placed under argon atmosphere and POCl3 was added dropwise (10 mL). The mixture was refluxed for 1h30. The mixture was cooled to room temperature, and poured into ice/water. The precipitating solid was filtered off, washed with water, cyclohexane and dried under pressure to give the desired 1,3,4-oxadiazole derivative.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

9
[ 28036-91-1 ]
[ 50868-68-3 ]
C₁₄H₉BrCl₂N₂O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate Reflux; Inert atmosphere;	1 General procedure for two steps synthesis of 1,3,4-oxadiazole derivatives 8-17 (Method A) and general procedure for one-step synthesis of 1,3,4-oxadiazole derivatives 8-28 (Method B) General procedure: Method A; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted hydrazide (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (2.5 eq, 50% solution in EtOAc) and triethylamine (3 eq), and the mixture was refluxed under argon atmosphere for 1h-24h. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature, and poured into ice/water. The precipitating solid was filtered off, washed with water, cyclohexan and dried under pressure to give the pure diacylhydrazine derivative.; The corresponding diacylhydrazine derivative was placed under argon atmosphere and POCl3 was added dropwise (10 mL). The mixture was refluxed for 1h30. The mixture was cooled to room temperature, and poured into ice/water. The precipitating solid was filtered off, washed with water, cyclohexane and dried under pressure to give the desired 1,3,4-oxadiazole derivative.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

10
[ 28036-91-1 ]
[ 50868-68-3 ]
2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-(3,4-dichlorophenyl)-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 160℃; Sealed tube; Inert atmosphere; Microwave irradiation;	5 General procedure for two steps synthesis of 1,3,4-oxadiazole derivatives 8-17 (Method A) and general procedure for one-step synthesis of 1,3,4-oxadiazole derivatives 8-28 (Method B) General procedure: Method B; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted hydrazide (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (3 eq, 50% solution in EtOAc) and triethylamine (5 eq). The reaction vessel was sealed under argon atmosphere and the mixture was heated under microwave conditions at 160°C for 20min to 30min. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature. The organic layer was washed twice with 1N HCl, once with H2O and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc or DCM/Methanol) to afford the desired 1,3,4-oxadiazole derivative.; 4.1.2.5 2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-(3,4-dichlorophenyl)-1,3,4-oxadiazole 10 1H NMR (DMSO-d6, 250 MHz): δ = 8.19 (d, J = 1.9 Hz, 1H), 7.95 (dd, J = 8.5 Hz and J = 2.0 Hz, 1H), 7.84 (d, J = 16.2 Hz, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.32 (d, J = 3.9 Hz, 1H), 7.22 (d, J = 3.9 Hz, 1H), 6.96 (d, J = 16.2 Hz, 1H); 13C NMR (DMSO-d6, 101 MHz): δ = 164.59, 162.18, 141.88, 135.31, 132.95, 132.46, 132.33, 132.12, 131.75, 128.80, 127.19, 124.39, 115.33, 109.33; LC/MS (ESI): 400.74 [M+H]+ and isotopic peaks: 402.73, 404.74; HRMS (TOF, ESI+) cald for C14H8N2OSCl2Br (M + H)+ 400.8918, found 400.8912; beige powder.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

11
[ 456-06-4 ]
[ 50868-68-3 ]
2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-(4-fluorophenyl)-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 160℃; Sealed tube; Inert atmosphere; Microwave irradiation;	7 General procedure for two steps synthesis of 1,3,4-oxadiazole derivatives 8-17 (Method A) and general procedure for one-step synthesis of 1,3,4-oxadiazole derivatives 8-28 (Method B) General procedure: Method B; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted hydrazide (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (3 eq, 50% solution in EtOAc) and triethylamine (5 eq). The reaction vessel was sealed under argon atmosphere and the mixture was heated under microwave conditions at 160°C for 20min to 30min. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature. The organic layer was washed twice with 1N HCl, once with H2O and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc or DCM/Methanol) to afford the desired 1,3,4-oxadiazole derivative.; 4.1.2.7 2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-(4-fluorophenyl)-1,3,4-oxadiazole 12 1H NMR (DMSO-d6, 400 MHz): δ = 8.15 (dd, J = 8.8 Hz, 1H), 8.13 (d, J = 8.8 Hz, 1H), 7.87 (d, J = 16.2 Hz, 1H), 7.48 (t, J = 8.8 Hz, 2H), 7.41 (d, J = 3.9 Hz, 1H), 7.31 (d, J = 3.9 Hz, 1H), 7.04 (d, J = 16.2 Hz, 1H); 13C NMR (DMSO-d6, 101 MHz): δ = 164.11, 163.02, 141.82, 132.38, 131.74, 131.52, 129.85, 129.76, 120.48, 120.46, 117.29, 117.07, 115.23, 109.42; LC/MS (ESI): 350.99 [M+H]+ and isotopic peak: 352.98; HRMS (TOF, ESI+) cald for C14H9N2OFSBr (M + H)+ 350.9303, found 350.9599; yellow powder.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

12
[ 3290-99-1 ]
[ 50868-68-3 ]
2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-(4-methoxyphenyl)-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
24%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 160℃; Sealed tube; Inert atmosphere; Microwave irradiation;	9 General procedure for two steps synthesis of 1,3,4-oxadiazole derivatives 8-17 (Method A) and general procedure for one-step synthesis of 1,3,4-oxadiazole derivatives 8-28 (Method B) General procedure: Method B; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted hydrazide (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (3 eq, 50% solution in EtOAc) and triethylamine (5 eq). The reaction vessel was sealed under argon atmosphere and the mixture was heated under microwave conditions at 160°C for 20min to 30min. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature. The organic layer was washed twice with 1N HCl, once with H2O and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc or DCM/Methanol) to afford the desired 1,3,4-oxadiazole derivative.; 4.1.2.9 2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-(4-methoxyphenyl)-1,3,4-oxadiazole 14 1H NMR (DMSO-d6, 250 MHz): δ = 8.03 (d, J = 8.4 Hz, 2H), 7.84 (d, J = 16.2 Hz, 1H), 7.41 (d, J = 3.5 Hz, 1H), 7.32 (d, J = 3.6 Hz, 1H), 7.18 (d, J = 8.5 Hz, 2H), 7.02 (d, J = 16.2 Hz, 1H), 3.88 (s, 3H); 13C NMR (DMSO-d6, 101 MHz): δ = 163.78, 163.67, 162.68, 141.99, 132.41, 131.66, 131.08, 129.05, 116.13, 115.44, 115.08, 109.67, 56.10; LC/MS (ESI): 362.86 [M+H]+ and isotopic peak: 364.89; HRMS (TOF, ESI+) cald for C15H12N2O2SBr (M + H)+ 362.9803, found 362.9804; beige powder.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

13
[ 339-59-3 ]
[ 50868-68-3 ]
2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 160℃; Sealed tube; Inert atmosphere; Microwave irradiation;	11 General procedure for two steps synthesis of 1,3,4-oxadiazole derivatives 8-17 (Method A) and general procedure for one-step synthesis of 1,3,4-oxadiazole derivatives 8-28 (Method B) General procedure: Method B; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted hydrazide (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (3 eq, 50% solution in EtOAc) and triethylamine (5 eq). The reaction vessel was sealed under argon atmosphere and the mixture was heated under microwave conditions at 160°C for 20min to 30min. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature. The organic layer was washed twice with 1N HCl, once with H2O and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc or DCM/Methanol) to afford the desired 1,3,4-oxadiazole derivative.; 4.1.2.11 2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-[4-(trifluoromethyl)phenyl]-1,3,4-oxadiazole 16 1H NMR (DMSO-d6, 250 MHz): δ = 8.30 (d, J = 8.1 Hz, 2H), 8.02 (d, J = 8.3 Hz, 2H), 7.93 (d, J = 16.2 Hz, 1H), 7.45 (d, J = 4.0 Hz, 1H), 7.33 (d, J = 3.9 Hz, 1H), 7.09 (d, J = 16.2 Hz, 1H); 13C NMR (DMSO-d6, 101 MHz): δ = 164.71, 162.82, 141.81, 132.48, 132.25, 132.12, 132.03, 127.98, 127.62, 126.95, 126.91, 125.65, 122.93, 115.53, 109.34; LC/MS (APCI): 400.86 [M+H]+ and isotopic peak: 402.72; HRMS (TOF, ESI+) cald for C15H9N2OF3SBr (M + H)+ 400.9571, found 400.9574; yellow powder.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

14
[ 39115-96-3 ]
[ 50868-68-3 ]
2-(3-bromophenyl)-5-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In ethyl acetate; at 160℃;Sealed tube; Inert atmosphere; Microwave irradiation;	General procedure: Method B; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted hydrazide (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (3 eq, 50% solution in EtOAc) and triethylamine (5 eq). The reaction vessel was sealed under argon atmosphere and the mixture was heated under microwave conditions at 160C for 20min to 30min. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature. The organic layer was washed twice with 1N HCl, once with H2O and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc or DCM/Methanol) to afford the desired 1,3,4-oxadiazole derivative.; 4.1.2.13 2-(3-bromophenyl)-5-[(E)-2-(5-bromothiophen-2-yl)ethenyl]- 1,3,4-oxadiazole 18 1H NMR (DMSO-d6, 300 MHz): delta = 8.22 (t, J = 1.6 Hz, 1H), 8.08 (dm, J = 8.1 Hz, 1H), 7.91 (d, J = 16.2 Hz, 1H), 7.85 (dm, J = 8.0 Hz, 1H), 7.59 (t, J = 8.0 Hz, 1H), 7.42 (d, J = 3.9 Hz, 1H), 7.31 (d, J = 3.9 Hz, 1H), 7.03 (d, J = 16.2 Hz, 1H); 13C NMR (DMSO-d6, 101 MHz): delta = 164.40, 162.50, 141.82, 135.18, 132.40, 132.10, 131.95, 131.83, 129.43, 126.10, 125.90, 122.93, 115.37, 109.27; LC/MS (ESI): 410.67 [M+H]+ and isotopic peaks: 412.73, 414.78; purity = 95%; HRMS (TOF, ESI+) cald for C14H9N2OSBr2 (M + H)+ 410.8802, found 410.8798; yellow powder. Yield = 49%.

Reference： [1]European Journal of Medicinal Chemistry,2016,vol. 109,p. 146 - 156

15
[ 19353-92-5 ]
[ 50868-68-3 ]
2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-[4-(N,N-dimethylamino)phenyl]-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 160℃; Sealed tube; Inert atmosphere; Microwave irradiation;	15 General procedure for two steps synthesis of 1,3,4-oxadiazole derivatives 8-17 (Method A) and general procedure for one-step synthesis of 1,3,4-oxadiazole derivatives 8-28 (Method B) General procedure: Method B; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted hydrazide (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (3 eq, 50% solution in EtOAc) and triethylamine (5 eq). The reaction vessel was sealed under argon atmosphere and the mixture was heated under microwave conditions at 160°C for 20min to 30min. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature. The organic layer was washed twice with 1N HCl, once with H2O and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc or DCM/Methanol) to afford the desired 1,3,4-oxadiazole derivative.; 4.1.2.15 2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-[(4-N,N-dimethyl)phenyl]-1,3,4-oxadiazole 20 1H RMN (DMSO-d6, 400 MHz): δ = 7.81 (d, J = 8.9 Hz, 2H), 7.72 (d, J = 16.1 Hz, 1H), 7.34 (d, J = 3.8 Hz, 1H), 7.25 (d, J = 3.8 Hz, 1H), 6.94 (d, J = 16.2 Hz, 1H), 6.80 (d, J = 9.0 Hz, 2H), 2.98 (s, 6H); 13C NMR (DMSO-d6, 101 MHz): δ = 164.52, 162.95, 152.89, 142.14, 132.35, 131.40, 130.30, 128.46, 114.75, 112.28, 110.07, 109.86, 40.18; LC/MS (ESI): 375.77 [M+H]+ and isotopic peak: 377.77; purity = 96%; HRMS (TOF, ESI+) cald for C16H15N3OSBr (M + H)+ 376.0119, found 376.0119; orange powder. Yield = 43%.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

16
[ 613-94-5 ]
[ 50868-68-3 ]
2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-phenyl-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
15%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 160℃; Sealed tube; Inert atmosphere; Microwave irradiation;	17 General procedure for two steps synthesis of 1,3,4-oxadiazole derivatives 8-17 (Method A) and general procedure for one-step synthesis of 1,3,4-oxadiazole derivatives 8-28 (Method B) General procedure: Method B; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted hydrazide (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (3 eq, 50% solution in EtOAc) and triethylamine (5 eq). The reaction vessel was sealed under argon atmosphere and the mixture was heated under microwave conditions at 160°C for 20min to 30min. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature. The organic layer was washed twice with 1N HCl, once with H2O and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc or DCM/Methanol) to afford the desired 1,3,4-oxadiazole derivative.; 4.1.2.17 2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-phenyl-1,3,4-oxadiazole 22 1H RMN (DMSO-d6, 400 MHz): δ = 8.04 (dd, J = 7.6 Hz and J = 1.9 Hz, 2H), 7.83 (d, J = 16.2 Hz, 1H), 7.62-7.56 (m, 3H), 7.38 (d, J = 3.9 Hz, 1H), 7.27 (d, J = 3.9 Hz, 1H), 7.01 (d, J = 16.1 Hz, 1H); 13C NMR (DMSO-d6, 101 MHz): δ = 164.15, 163.81, 141.91, 132.60, 132.43, 131.85, 131.55, 129.96, 127.16, 123.80, 115.29, 109.53; LC/MS (ESI): 332.80 [M+H]+ and isotopic peak: 334.76; purity = 96%; HRMS (TOF, ESI+) cald for C14H10N2OSBr (M + H)+ 332.9697, found 332.9696; yellow powder. Yield = 15%.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

17
[ 536-40-3 ]
[ 50868-68-3 ]
2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-(4-chlorophenyl)-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 160℃; Sealed tube; Inert atmosphere; Microwave irradiation;	19 General procedure for two steps synthesis of 1,3,4-oxadiazole derivatives 8-17 (Method A) and general procedure for one-step synthesis of 1,3,4-oxadiazole derivatives 8-28 (Method B) General procedure: Method B; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted hydrazide (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (3 eq, 50% solution in EtOAc) and triethylamine (5 eq). The reaction vessel was sealed under argon atmosphere and the mixture was heated under microwave conditions at 160°C for 20min to 30min. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature. The organic layer was washed twice with 1N HCl, once with H2O and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc or DCM/Methanol) to afford the desired 1,3,4-oxadiazole derivative.; 4.1.2.19 2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-(4-chlorophenyl)-1,3,4-oxadiazole 24 1H NMR (DMSO-d6, 250 MHz): δ = 8.04 (d, J = 8.6 Hz, 2H), 7.83 (d, J = 16.2 Hz, 1H), 7.66 (d, J = 8.6 Hz, 2H), 7.37 (d, J = 3.9 Hz, 1H), 7.27 (d, J = 3.8 Hz, 1H), 7.00 (d, J = 16.2 Hz, 1H); 13C NMR (DMSO-d6, 101 MHz): δ = 164.31, 163.09, 141.87, 137.32, 132.45, 131.86, 131.76, 130.14, 128.94, 122.72, 115.35, 109.43; LC/MS (ESI): 366.74 [M+H]+ and isotopic peak: 368.72; purity = 95%; HRMS (TOF, ESI+) cald for C14H9N2OSClBr (M + H)+ 366.9307, found 366.9306; yellow powder. Yield = 38%.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

18
[ 50868-68-3 ]
[ 5933-32-4 ]
2-(4-bromophenyl)-5-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 160℃; Sealed tube; Inert atmosphere; Microwave irradiation;	20 General procedure for two steps synthesis of 1,3,4-oxadiazole derivatives 8-17 (Method A) and general procedure for one-step synthesis of 1,3,4-oxadiazole derivatives 8-28 (Method B) General procedure: Method B; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted hydrazide (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (3 eq, 50% solution in EtOAc) and triethylamine (5 eq). The reaction vessel was sealed under argon atmosphere and the mixture was heated under microwave conditions at 160°C for 20min to 30min. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature. The organic layer was washed twice with 1N HCl, once with H2O and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc or DCM/Methanol) to afford the desired 1,3,4-oxadiazole derivative.; 4.1.2.20 2-(4-bromophenyl)-5-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-1,3,4-oxadiazole 25 1H RMN (DMSO-d6, 400 MHz): δ = 8.02 (d, J = 8.6 Hz, 2H), 7.91 (d, J = 16.2 Hz, 1H), 7.86 (d, J = 8.7 Hz, 2H), 7.43 (d, J = 3.9 Hz, 1H), 7.33 (d, J = 3.9 Hz, 1H), 7.06 (d, J = 16.2 Hz, 1H); 13C NMR (DMSO-d6, 101 MHz): δ = 164.26, 163.13, 141.81, 133.00, 132.39, 131.84, 131.72, 128.99, 126.16, 122.98, 115.33, 109.35; LC/MS (ESI): 410.68 [M+H]+ and isotopic peaks: 412.69, 414.69; purity = 97%; HRMS (TOF, ESI+) cald for C14H9N2OSBr2 (M + H)+ 410.8802, found 410.8805; yellow powder. Yield = 27%.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

19
[ 499-55-8 ]
[ 50868-68-3 ]
2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-(3-fluorophenyl)-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 160℃; Sealed tube; Inert atmosphere; Microwave irradiation;	21 General procedure for two steps synthesis of 1,3,4-oxadiazole derivatives 8-17 (Method A) and general procedure for one-step synthesis of 1,3,4-oxadiazole derivatives 8-28 (Method B) General procedure: Method B; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted hydrazide (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (3 eq, 50% solution in EtOAc) and triethylamine (5 eq). The reaction vessel was sealed under argon atmosphere and the mixture was heated under microwave conditions at 160°C for 20min to 30min. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature. The organic layer was washed twice with 1N HCl, once with H2O and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc or DCM/Methanol) to afford the desired 1,3,4-oxadiazole derivative.; 4.1.2.21 2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-(3-fluorophenyl)-1,3,4-oxadiazole 26 1H RMN (DMSO-d6, 250 MHz): δ = 7.99 (d, J = 16.1 Hz, 1H), 7.99-7.91 (m, 2H), 7.75 (dd, J = 7.9 Hz and J = 2.1 Hz, 1H), 7.58 (td, J = 8.7 Hz and J = 1.9 Hz, 1H), 7.49 (d, J = 3.9 Hz, 1H), 7.39 (d, J = 3.8 Hz, 1H), 7.13 (d, J = 16.2 Hz, 1H); 13C NMR (DMSO-d6, 101 MHz): δ = 164.41, 162.83, 141.85, 132.46, 132.39 (C-F), 132.31, 131.96, 131.87, 125.80, 123.41, 119.62, 119.41, 115.43, 114.08, 113.84, 109.34; LC/MS (ESI): 350.78 [M+H]+ and isotopic peak: 352.87; purity = 97%; HRMS (TOF, ESI+) cald for C14H9N2OSBrF (M + H)+ 350.9603, found 350.9605; yellow powder. Yield = 33%.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

20
[ 50868-68-3 ]
[ 62899-78-9 ]
2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-(3,5-dichlorophenyl)-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 160℃; Sealed tube; Inert atmosphere; Microwave irradiation;	22 General procedure for two steps synthesis of 1,3,4-oxadiazole derivatives 8-17 (Method A) and general procedure for one-step synthesis of 1,3,4-oxadiazole derivatives 8-28 (Method B) General procedure: Method B; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted hydrazide (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (3 eq, 50% solution in EtOAc) and triethylamine (5 eq). The reaction vessel was sealed under argon atmosphere and the mixture was heated under microwave conditions at 160°C for 20min to 30min. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature. The organic layer was washed twice with 1N HCl, once with H2O and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc or DCM/Methanol) to afford the desired 1,3,4-oxadiazole derivative.; 4.1.2.22 2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-(3,5-dichlorophenyl)-1,3,4-oxadiazole 27 1H RMN (DMSO-d6, 400 MHz): δ = 8.02 (d, J = 1.9 Hz, 2H), 7.90 (d, J = 16.1 Hz, 1H), 7.87 (t, J = 1.9 Hz, 1H), 7.36 (d, J = 3.9 Hz, 1H), 7.26 (d, J = 3.9 Hz, 1H), 6.99 (d, J = 16.1 Hz, 1H); 13C NMR (DMSO-d6, 101 MHz): δ = 164.72, 161.69, 141.81, 135.75, 132.48, 132.43, 131.94, 131.81, 126.98, 125.56, 115.62, 109.10; LC/MS (ESI): 400.71 [M+H] + and isotopic peaks: 402.70, 404.68; purity = 98%; HRMS (TOF, ESI+) cald for C14H8N2OSCl2Br (M + H)+ 400.8918, found 400.8921; yellow powder. Yield = 55%.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

21
[ 5785-06-8 ]
[ 50868-68-3 ]
2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-(3-methoxyphenyl)-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
18%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 160℃; Sealed tube; Inert atmosphere; Microwave irradiation;	23 General procedure for two steps synthesis of 1,3,4-oxadiazole derivatives 8-17 (Method A) and general procedure for one-step synthesis of 1,3,4-oxadiazole derivatives 8-28 (Method B) General procedure: Method B; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted hydrazide (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (3 eq, 50% solution in EtOAc) and triethylamine (5 eq). The reaction vessel was sealed under argon atmosphere and the mixture was heated under microwave conditions at 160°C for 20min to 30min. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature. The organic layer was washed twice with 1N HCl, once with H2O and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc or DCM/Methanol) to afford the desired 1,3,4-oxadiazole derivative.; 4.1.2.23 2-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-5-(3-methoxyphenyl)-1,3,4-oxadiazole 28 1H RMN (DMSO-d6, 250 MHz): δ = 7.96 (d, J = 16.2 Hz, 1H), 7.73 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 1.8 Hz, 1H), 7.59 (d, J = 7.9 Hz, 1H), 7.49 (d, J = 4.0 Hz, 1H), 7.38 (d, J = 3.9 Hz, 1H), 7.28 (dd, J = 8.2 Hz and J = 2.6 Hz, 1H), 7.12 (d, J = 16.2 Hz, 1H), 3.93 (s, 3H); 13C NMR (DMSO-d6, 101 MHz): δ = 164.21, 163.72, 160.25, 141.94, 132.46, 131.86, 131.65, 131.29, 124.98, 119.48, 118.52, 115.34, 112.08, 109.51, 56.04; LC/MS (ESI): 362.80 [M+H]+ and isotopic peak: 364.80; purity = 98%; HRMS (TOF, ESI+) cald for C15H12N2O2SBr (M + H)+ 362.9803, found 362.9807; brown solid. Yield = 18%.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

22
[ 5033-28-3 ]
[ 50868-68-3 ]
(E)-[amino(4-chlorophenyl)methylidene]amino-(2E)-3-(5-bromothiophen-2-yl)prop-2-enoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
9%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate Reflux; Inert atmosphere;	1 General procedure for two steps synthesis (Method C) and one-step synthesis (Method D) of 1,2,4-oxadiazole derivatives 33-36 General procedure: Method C; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted amidoxime (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (2.5 eq, 50% solution in EtOAc) and triethylamine (3 eq-5 eq), and the mixture was refluxed under argon atmosphere for 24h. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature and poured into ice/water. The aqueous layer was extracted twice with EtOAc and then the organic layer was washed twice with saturated NaHCO3, and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc) to afford the desired acylamidoxime. An example of the acylamidoxime derivative 29 synthesis is given below.; 4.1.3.1 (E)-[amino(4-chlorophenyl)methylidene]amino-(2E)-3-(5-bromothiophen-2-yl)prop-2-enoate 29 1H NMR (acetone-d6, 250 MHz): δ = 7.72 (d, J = 8.8 Hz, 2H), 7.70 (d, J = 15.7 Hz, 1H), 7.36 (d, J = 8.8 Hz, 2H), 7.18 (d, J = 3.9 Hz, 1H), 7.09 (d, J = 3.9 Hz, 1H), 6.38 (bs, 2H), 6.33 (d, J = 15.8 Hz, 1H); LC/MS (ESI): 382.74 [M-H]- and isotopic peak: 384.81, 384.80 [M+H]+ and isotopic peak: 386.85; purity = 98%; beige powder. Yield = 9%. The corresponding acylamidoxime (1 eq) was placed under argon atmosphere, anhydrous THF (3 mL) and TBAF (0.1 eq, 1 M in THF) was added. The mixture was stirred at room temperature for 16-18 h. The completion of reaction was confirmed by TLC. The solvent was evaporated and EtOAc was added. The organic layer was washed twice with water and twice with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

23
[ 22179-77-7 ]
[ 50868-68-3 ]
5-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-3-(3-chlorophenyl)-1,2,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
14%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 160℃; for 0.5h; Sealed tube; Inert atmosphere; Microwave irradiation;	3 General procedure for two steps synthesis (Method C) and one-step synthesis (Method D) of 1,2,4-oxadiazole derivatives 33-36 General procedure: Method D; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (3 eq, 50% solution in EtOAc) and triethylamine (5 eq). The reaction vessel was sealed under argon atmosphere and the mixture was heated under microwave conditions at 160°C for 30min. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature. The organic layer was washed twice with 1N HCl, once with H2O and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc) to afford the desired 1,2,4-oxadiazole derivative.; 4.1.3.3 5-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-3-(3-chlorophenyl)-1,2,4-oxadiazole 34 1H NMR (DMSO-d6, 400 MHz): δ = 8.07 (d, J = 16.0 Hz, 1H), 8.02-7.97 (m, 2H), 7.66-7.59 (m, 1H), 7.63 (t, J = 7.8 Hz, 1H), 7.52 (d, J = 4.0 Hz, 1H), 7.35 (d, J = 3.9 Hz, 1H), 7.09 (d, J = 16.1 Hz, 1H); 13C NMR (DMSO-d6, 101 MHz): δ = 175.79, 167.43, 141.30, 135.46, 134.40, 133.56, 132.54, 131.93, 131.83, 128.70, 127.05, 126.10, 116.80, 109.27; LC/MS (APCI): 366.59 [M-H-] and isotopic peak 368.56, 368.70 [M + H+] and isotopic peak: 370.10; HRMS (TOF, ESI+) cald for C14H9N2OSClBr (M + H)+ 366.9307, found 366.9310; pale orange powder. Method C - Two-step conversion yield determined by LC/MS = 8%.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

24
[ 22179-77-7 ]
[ 50868-68-3 ]
C₁₄H₁₀BrClN₂O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
9%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate Reflux; Inert atmosphere;	1 General procedure for two steps synthesis (Method C) and one-step synthesis (Method D) of 1,2,4-oxadiazole derivatives 33-36 General procedure: Method C; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted amidoxime (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (2.5 eq, 50% solution in EtOAc) and triethylamine (3 eq-5 eq), and the mixture was refluxed under argon atmosphere for 24h. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature and poured into ice/water. The aqueous layer was extracted twice with EtOAc and then the organic layer was washed twice with saturated NaHCO3, and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc) to afford the desired acylamidoxime.; The corresponding acylamidoxime (1 eq) was placed under argon atmosphere, anhydrous THF (3 mL) and TBAF (0.1 eq, 1 M in THF) was added. The mixture was stirred at room temperature for 16-18 h. The completion of reaction was confirmed by TLC. The solvent was evaporated and EtOAc was added. The organic layer was washed twice with water and twice with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

25
N'-hydroxy-4-(trifluoromethoxy) benzene-1-carboximidamide [ No CAS ]
[ 50868-68-3 ]
5-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
11%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 160℃; for 0.5h; Sealed tube; Inert atmosphere; Microwave irradiation;	4 General procedure for two steps synthesis (Method C) and one-step synthesis (Method D) of 1,2,4-oxadiazole derivatives 33-36 General procedure: Method D; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (3 eq, 50% solution in EtOAc) and triethylamine (5 eq). The reaction vessel was sealed under argon atmosphere and the mixture was heated under microwave conditions at 160°C for 30min. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature. The organic layer was washed twice with 1N HCl, once with H2O and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc) to afford the desired 1,2,4-oxadiazole derivative.; 4.1.3.4 5-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-3-[4-trifluoro(methoxy)phenyl]-1,2,4-oxadiazole 35 1H NMR (DMSO-d6, 400 MHz): δ = 8.07 (d, J = 8.9 Hz, 2H), 7.97 (d, J = 16.1 Hz, 1H), 7.50 (d, J = 8.8 Hz, 2H), 7.44 (d, J = 4.0 Hz, 1H), 7.26 (d, J = 3.9 Hz, 1H), 7.01 (d, J = 16.1 Hz, 1H); 13C NMR (DMSO-d6, 101 MHz): δ = 175.73, 167.50, 150.91, 150.89, 141.31, 135.35, 133.53, 132.53, 129.73, 125.87, 122.11, 116.76, 109.35; LC/MS (ESI): 415.26 [M-H]- and isotopic peak: 417.22; HRMS (TOF, ESI+) cald for C15H9N2O2F3SBr (M + H)+ 416.9520, found 416.9520; yellow powder. Method C - Two-step conversion yield determined by LC/MS = 5%.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

26
N'-hydroxy-4-(trifluoromethoxy) benzene-1-carboximidamide [ No CAS ]
[ 50868-68-3 ]
C₁₅H₁₀BrF₃N₂O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
6%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate Reflux; Inert atmosphere;	1 General procedure for two steps synthesis (Method C) and one-step synthesis (Method D) of 1,2,4-oxadiazole derivatives 33-36 General procedure: Method C; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted amidoxime (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (2.5 eq, 50% solution in EtOAc) and triethylamine (3 eq-5 eq), and the mixture was refluxed under argon atmosphere for 24h. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature and poured into ice/water. The aqueous layer was extracted twice with EtOAc and then the organic layer was washed twice with saturated NaHCO3, and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc) to afford the desired acylamidoxime.; The corresponding acylamidoxime (1 eq) was placed under argon atmosphere, anhydrous THF (3 mL) and TBAF (0.1 eq, 1 M in THF) was added. The mixture was stirred at room temperature for 16-18 h. The completion of reaction was confirmed by TLC. The solvent was evaporated and EtOAc was added. The organic layer was washed twice with water and twice with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

27
[ 22179-86-8 ]
[ 50868-68-3 ]
5-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-3-[(4-trifluoromethyl)phenyl]-1,2,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 160℃; for 0.5h; Sealed tube; Inert atmosphere; Microwave irradiation;	5 General procedure for two steps synthesis (Method C) and one-step synthesis (Method D) of 1,2,4-oxadiazole derivatives 33-36 General procedure: Method D; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (3 eq, 50% solution in EtOAc) and triethylamine (5 eq). The reaction vessel was sealed under argon atmosphere and the mixture was heated under microwave conditions at 160°C for 30min. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature. The organic layer was washed twice with 1N HCl, once with H2O and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc) to afford the desired 1,2,4-oxadiazole derivative.; 4.1.3.5 5-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-3-[(4-trifluoromethyl)phenyl]-1,2,4-oxadiazole 36 1H NMR (DMSO-d6, 400 MHz): δ = 8.24 (d, J = 8.1 Hz, 2H), 8.08 (d, J = 16.1 Hz, 1H), 7.96 (d, J = 8.3 Hz, 2H), 7.53 (d, J = 4.0 Hz, 1H), 7.35 (d, J = 3.9 Hz, 1H), 7.11 (d, J = 16.1 Hz, 1H); 13C NMR (DMSO-d6, 101 MHz): δ = 175.95, 167.52, 141.28, 135.51, 133.62, 132.54, 132.01, 128.33, 126.78, 126.75, 126.71, 126.67, 125.66, 122.96, 116.85, 109.25; LC/MS (ESI): 401.14 [M-H]-; HRMS (TOF, ESI+) cald for C15H9N2OF3SBr (M + H)+ 400.9571, found 400.9570; yellow powder. Method C - Two-step conversion yield determined by LC/MS = 3%.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

28
[ 5033-28-3 ]
[ 50868-68-3 ]
5-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-3-(4-chlorophenyl)-1,2,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
7%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In ethyl acetate at 160℃; for 0.5h; Sealed tube; Inert atmosphere; Microwave irradiation;	2 General procedure for two steps synthesis (Method C) and one-step synthesis (Method D) of 1,2,4-oxadiazole derivatives 33-36 General procedure: Method D; To a stirred solution of acrylic acid (200mg, 1 eq) and substituted (1 eq) in dry ethyl acetate (5-10mL) were added dropwise T3P (3 eq, 50% solution in EtOAc) and triethylamine (5 eq). The reaction vessel was sealed under argon atmosphere and the mixture was heated under microwave conditions at 160°C for 30min. The completion of reaction was confirmed by TLC. The mixture was cooled to room temperature. The organic layer was washed twice with 1N HCl, once with H2O and once with brine. The organic layer was dried under Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (cyclohexan/EtOAc) to afford the desired 1,2,4-oxadiazole derivative.; 4.1.3.2 5-[(E)-2-(5-bromothiophen-2-yl)ethenyl]-3-(4-chlorophenyl)-1,2,4-oxadiazole 33 1H NMR (DMSO-d6, 400 MHz): δ = 8.02 (d, J = 8.5 Hz, 2H), 7.99 (d, J = 16.3 Hz, 1H), 7.62 (d, J = 8.5 Hz, 2H), 7.48 (d, J = 4.0 Hz, 1H), 7.30 (d, J = 3.9 Hz, 1H), 7.05 (d, J = 16.2 Hz, 1H); 13C NMR (DMSO-d6, 101 MHz): δ = 175.74, 167.75, 141.37, 136.84, 135.39, 133.61, 132.60, 129.99, 129.33, 125.62, 116.82, 109.42; LC/MS (ESI): 364.80 [M-H]- and isotopic peak: 366.77, 366.73 [M+H]+ and isotopic peak: 368.77; HRMS (TOF, ESI+) cald for C14H9N2OSClBr (M + H)+ 366.9307, found 366.9307; yellow powder. Method C - Two-step conversion yield determined by LC/MS = 8%.

Reference： [1]Benmansour, Fatiha; Eydoux, Cécilia; Querat, Gilles; De Lamballerie, Xavier; Canard, Bruno; Alvarez, Karine; Guillemot, Jean-Claude; Barral, Karine [European Journal of Medicinal Chemistry, 2016, vol. 109, p. 146 - 156]

29
[ 50868-68-3 ]
[ 154593-58-5 ]

Reference： [1]Organic Letters,2016,vol. 18,p. 5468 - 5471

30
[ 50868-68-3 ]
[ 95-76-1 ]
(2E)-3-(5-bromothiophen-2-yl)-N-(3,4-dichlorophenyl)prop-2-enamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran; dichloromethane at 20℃; for 5h;	1 Procedure A General procedure: To a stirred solution of 3-(Thien-2-yl)- or 3-(Thiazol-5-yl)acrylic acid derivative (1.5eq, 200mg) and substituted aniline (l eq) in dry dichloromethane or in dry THF (20mL), l -(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2eq) and DMAP (2eq) were added. The reaction mixture was stirred at room temperature for 5h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was poured into IN aqueous solution of hydrochloric acid (lOmL). At this stage, compounds 9, 33, 53 and 99 precipitated. Precipitates were filtered off, washed with water and dried to afford pure hydrochloride salts. For all other compounds, the organic layer was washed twice with IN aqueous solution of hydrochloric acid (IN), then twice with saturated NaHCC , water and brine. The organic layer was dried under MgS04, then filtered off and concentrated under reduced pressure. The crude product was purified by flash chromatography (cyclohexane/ethyl acetate or dichloromethane/methanol) afforded the final product.

Reference： [1]Current Patent Assignee: INSTITUT CURIE; NATIONAL INSTITUTE OF HEALTH AND MEDICAL RESEARCH; CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE; AIX-MARSEILLE UNIVERSITY - WO2017/102014, 2017, A1 Location in patent: Page/Page column 28; 29

31
[ 50868-68-3 ]
[ 28948-60-9 ]

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 2448 - 2466

32
[ 541-41-3 ]
[ 50868-68-3 ]
[ 28948-60-9 ]

Yield	Reaction Conditions	Operation in experiment
52%	Stage #1: chloroformic acid ethyl ester; (E)-3-(5-bromo-2-thienyl)-2-propenoic acid With triethylamine In acetone at 0℃; for 1.5h; Stage #2: With sodium azide In water; acetone at 0℃; for 0.25h; Stage #3: With tributyl-amine In diphenylether; dichloromethane at 240℃; for 0.916667h;	[0099] 2-Bromothieno[3,2-c]pyridin-4(5Lf)-one (6). Et3N (6.02 mL, 42.9 mmol) was added to a solution of (A)-3 -(5 -bromothiophen-2-yl (acrylic acid (5, 5.00 g, 21.4 mmol) in acetone (55 mL) at 0 °C (ice-bath). Ethyl chloroformate (6.25 mL, 64.3 mmol) was then added, and the reaction mixture was stirred at 0 °C for 1.5 h. A solution of NaN3 (2.09 g, 32.1 mmol) in H2O (16 mL) was added to this reaction mixture slowly at 0 °C (ice-bath). The mixture became homogeneous, and then a solid began to precipitate. Stirring was continued for 15 min. The reaction mixture was poured into ice-chilled H2O (30 mL) and extracted with EtOAc (3 x 30 mL). The combined organic layers were dried (MgSCL), filtered and concentrated to give crude acyl azide as a tan solid that was used for the next step without further purification. (0147) [00100] A 3-neck flask fitted with a stopper, addition funnel, and condenser was charged with BU3N (6.63 mL, 27.8 mmol) and PI12C) (20 mL). The solution was heated to 240 °C. The addition funnel was charged with a solution of the crude acyl azide (5.53 g, 21.4 mmol) in CH2CI2 (50 mL). The acyl azide solution was added to the hot reaction mixture over a period of ca. 40 min, allowing the CH2CI2 to boil off. The mixture was stirred at 240 °C for another 15 min, cooled to rt, and hexanes (20 mL) was added, at which point a solid began to precipitate. The hexane layer was decanted, and the remaining residue was suspended in EtOAc (15 mL). A tan solid precipitated out of solution and was filtered to give 6 (2.56 g, 52%) : Mp >250 °C; IR (ATR) Vmax 2809, 1637, 1607, 1513, 1472, 1274, 1222, 1144, 994, 928, 803, 762, 692 cm 1; NMR (400 MHz, DMSO-de) d 11.54 (brs, 1 H), 7.54 (d, J= 0.4 Hz, 1 H), 7.28-7.25 (m, 1 H), 6.81 (d, J= 6.8 Hz, 1 H); 13C NMR (100 MHz, DMSO-de) d 157.5, 149.7, 130.7, 130.4, 126.8, 111.4, 100.5; HRMS (ESI+) m/z calcd for C7H5ONSBr (M+H) 229.9270, found 229.9270.

Reference： [1]Current Patent Assignee: COMMONWEALTH SYSTEM OF HIGHER EDUCATION - WO2020/102245, 2020, A1 Location in patent: Paragraph 0084; 00100

33
[ 541-41-3 ]
[ 50868-68-3 ]
C₈H₄BrN₃O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: chloroformic acid ethyl ester; (E)-3-(5-bromo-2-thienyl)-2-propenoic acid With triethylamine In water; acetone at 0℃; for 0.5h; Inert atmosphere; Stage #2: With sodium azide In water; acetone at 0℃; Inert atmosphere;	2-Bromothieno[3,2-c]pyridin-4(5H)-one (SI-3). Triethylamine (6.63 mL, 47.2 mmol) was added to a solution of(E)-3-(5-bromothiophen-2-yl)acrylic acid (SI-2, 5.50 g, 23.6 mmol) in acetone (55 mL) at 0 °C (ice-bath). Subsequently, ethyl chloroformate (6.76 mL, 70.8 mmol) was added, and the reaction mixture was stirred at 0 °C for 30 min. A solution of NaN3 (2.30 g, 35.4 mmol) in H2O (17 mL) was slowly added to the reaction mixture at 0°C. The mixture became homogeneous before a solid began to precipitate. The mixture was stirred for 15 min.The reaction mixture was poured into ice-chilled H2O (30 mL), extracted with EtOAc (3 x 40 mL), and thecombined organic layers were dried (MgSO4), filtered, and concentrated to give crude acyl azide as a tan solidthat was used for the next step without further purification.

Reference： [1]Rastelli, Ettore J.; Sannino, Sara; Hart, Duncan J.; Sharlow, Elizabeth R.; Lazo, John S.; Brodsky, Jeffrey L.; Wipf, Peter [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 46]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	50868-68-3	MDL No. :	MFCD03002751
Formula :	C₇H₅BrO₂S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	N/A
M.W :	233.08 g/mol	Pubchem ID :	-
Synonyms :

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P330-P363-P501	UN#:	N/A
Hazard Statements:	H302-H312-H332	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. 50868-68-3 ]

Quality Control of [ 50868-68-3 ]

Related Doc. of [ 50868-68-3 ]

Product Details of [ 50868-68-3 ]

Safety of [ 50868-68-3 ]

Application In Synthesis of [ 50868-68-3 ]

[ 50868-68-3 ] Synthesis Path-Upstream 1~1

[ 50868-68-3 ] Synthesis Path-Downstream 1~33

Related Functional Groups of
[ 50868-68-3 ]

Bromides

Alkenyls

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

[ CAS No. 50868-68-3 ]

Quality Control of [ 50868-68-3 ]

Related Doc. of [ 50868-68-3 ]

Product Details of [ 50868-68-3 ]

Safety of [ 50868-68-3 ]

Application In Synthesis of [ 50868-68-3 ]

[ 50868-68-3 ] Synthesis Path-Upstream 1~1

[ 50868-68-3 ] Synthesis Path-Downstream 1~33

Related Functional Groups of [ 50868-68-3 ]

Bromides

Alkenyls

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 50868-68-3 ]