Name: 22227-25-4|3-(Trifluoromethyl)benzohydrazide|97%
Brand: Ambeed
SKU: A313180
Rating: 95 (22 reviews)

1
[ 22227-25-4 ]
[ 109-90-0 ]
[ 129521-44-4 ]

Yield	Reaction Conditions	Operation in experiment
29%	In tetrahydrofuran for 17h;

Reference： [1]Kane; Baron; Dudley; Sorensen; Staeger; Miller [Journal of Medicinal Chemistry, 1990, vol. 33, # 10, p. 2772 - 2777]

2
[ 75-15-0 ]
[ 22227-25-4 ]
[ 108413-50-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide In ethanol Heating;
	Stage #1: carbon disulfide; 3-(trifluoromethyl)benzene-1-carbohydrazide With sodium hydroxide Stage #2: With hydrogenchloride

Reference： [1]Dodd, Dharmpal S.; Shen, Zhongqi; Nishi, Takao; Graber, Norma; Bealls, Dawson; Fong, Miranda; Ebert, Tracy [Bioorganic and Medicinal Chemistry Letters, 1996, vol. 6, # 22, p. 2693 - 2698]
[2]Yu, Gang; Chen, Shunhong; He, Feng; Luo, Dexia; Zhang, Yu; Wu, Jian [Turkish Journal of Chemistry, 2019, vol. 43, # 4, p. 1075 - 1085]

3
[ 22227-25-4 ]
4-Methoxy-3,5-dimethyl-2-[5-(3-trifluoromethyl-phenyl)-[1,3,4]oxadiazol-2-ylsulfanylmethyl]-pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: KOH / ethanol / Heating 2: K₂CO₃ / acetone / Heating

Reference： [1]Dodd, Dharmpal S.; Shen, Zhongqi; Nishi, Takao; Graber, Norma; Bealls, Dawson; Fong, Miranda; Ebert, Tracy [Bioorganic and Medicinal Chemistry Letters, 1996, vol. 6, # 22, p. 2693 - 2698]

4
[ 22227-25-4 ]
4-Methoxy-3,5-dimethyl-2-[5-(3-trifluoromethyl-phenyl)-[1,3,4]oxadiazole-2-sulfinylmethyl]-pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: KOH / ethanol / Heating 2: K₂CO₃ / acetone / Heating 3: m-CPBA / CH₂Cl₂

Reference： [1]Dodd, Dharmpal S.; Shen, Zhongqi; Nishi, Takao; Graber, Norma; Bealls, Dawson; Fong, Miranda; Ebert, Tracy [Bioorganic and Medicinal Chemistry Letters, 1996, vol. 6, # 22, p. 2693 - 2698]

5
[ 22227-25-4 ]
[ 129521-48-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 29 percent / tetrahydrofuran / 17 h 2: 52 percent / aq. NaOH / 23 h / Heating

Reference： [1]Kane; Baron; Dudley; Sorensen; Staeger; Miller [Journal of Medicinal Chemistry, 1990, vol. 33, # 10, p. 2772 - 2777]

6
[ 22227-25-4 ]
[ 129521-50-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 29 percent / tetrahydrofuran / 17 h 2: 52 percent / aq. NaOH / 23 h / Heating 3: 41 percent / aq. NaOH / ethanol / 24 h

Reference： [1]Kane; Baron; Dudley; Sorensen; Staeger; Miller [Journal of Medicinal Chemistry, 1990, vol. 33, # 10, p. 2772 - 2777]

7
[ 700805-72-7 ]
[ 22227-25-4 ]
[ 863030-65-3 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: N-[4-(aminosulfonyl)phenyl]-N'-cyanocarbamidic acid phenyl ester; 3-(trifluoromethyl)benzene-1-carbohydrazide With pyridine at 20 - 85℃; for 4.08333 - 4.16667h; Stage #2: With sodium chloride at 0 - 5℃; for 0.5h;	33 To a clean, dry reaction tube was sequentially charged 3- (trifluoromethyl) benzoic hydrazide (0.94 g, 4.36 mmol), N- [4- (aminosulfonyl) phenyl]-N'-cyanocarbamidic acid phenyl ester (1.34 g, 4.15 mmol) and pyridine (10 mL). The suspension was stirred at room temperature for 5-10 min to effect solution after which time the reaction mixture was heated to 83°C and stirred at 83-85°C for 4 h. After 4 h the reaction mixture was cooled to room temperature and then added dropwise to of a vigorously stirred mixture of ice-H20 (ca 200 mL). A fluffy, off-white solid precipitated. Solid sodium chloride (ca 20-25 gm) was added to the suspension which was stirred at 0-5°C for 30 min and then filtered. The solid was washed with H20 (ca 100 mL) and was air dried for 1 h. The damp solid was dried in a vacuum oven at 80°C under a stream of nitrogen for 12 h to yield crude N3- [ (4- aminosulfonyl) phenyl]-1- [3'- (trifluoromethyl) benzoyl]-1 H-1, 2, 4-triazole-3, 5- diamine as an off-white solid. The crude product was dissolved in DMSO (4 mL) and purified on a silica gel column (30 g) using a mixture of ethyl acetate/n-heptane (70/30). The product containing fractions were combined and evaporated to yield an oily yellow solid containing residual DMSO, which was suspended in water (60 mL) and stirred at 50-55°C for 30 min. The suspension was cooled to room temperature and filtered. The solid was then washed with water (30 mL). The product was dried in a vacuum oven at 80°C for 16 h to yield N3- [ (4- aminosulfonyl) phenyl]-1- [3'- (trifluoromethyl) benzoyl]-1 H-1, 2, 4-triazole-3, 5- diamine as a pale yellow solid. HPLC purity: 98.5% m. p. 251.0-253. 0°C MS: [M+H] +=427, [M+Na]+=449 1H NMR (300 MHz, DMSO-d6) : zu 7.15 (2H, s), 7.60-7. 66 (4H, m), 7.84 (1 H, t), 7.95 (2H, br s), 8.07 (1 H, d), 8.33 (1 H, d), 8.72 (1 H, s), 9.87 (1 H, s) Elemental Analysis for C16Hl3F3N603S ; MW=426.38 Calculated : C, 45.07 ; H, 3.07 ; N, 19.71 ; F, 13.37 ; S, 7.52 Found: C, 44.79 ; H, 2.94 ; N, 19.46 ; F, 12.92 ; S, 7.66

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2005/77922, 2005, A2 Location in patent: Page/Page column 56-57

8
[ 51362-49-3 ]
[ 22227-25-4 ]
[ 218157-36-9 ]

Yield	Reaction Conditions	Operation in experiment
107 mg (54%)	In pyridine	1 N'-(2-Phenoxypyridine-3-carbonyl)-3-(trifluoromethyl)benzhydrazide EXAMPLE 1 N'-(2-Phenoxypyridine-3-carbonyl)-3-(trifluoromethyl)benzhydrazide A solution of 3-(trifluoromethyl)benzhydrazide (102.1 mg, 0.5 mmol), 2-phenoxypyridine-3-carbonyl chloride (117 mg, 0.5 mmol) in pyridine (5 mL) was refluxed for 2 h. It was evaporated in vacuo and the residue was purified by column chromatography (silica gel, EtOAc/CH2Cl2=4:1) to give 107 mg (54%) of the title compound. 1H NMR (CDCl3): 10.88 (d, J=6.3 Hz, 1H), 9.80 (d, J=6.3 Hz, 1H), 8.60 (m, 1H), 8.30 (m, 1H), 8.17 (s, 1H), 8.06 (d, J=8.1 Hz, 1H), 7.81 (d, J=7.8 Hz, 1H), 7.61 (t, J=7.2 Hz, 1H), 7.51-7.46 (m, 2H), 7.34-7.17 (m, 4H).

Reference： [1]Current Patent Assignee: IMMUNE PHARMACEUTICALS INC - US2003/13743, 2003, A1

9
[ 541-41-3 ]
[ 22227-25-4 ]
2-[3-(trifluoromethyl)benzoyl]-hydrazinecarboxylic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With pyridine In water; N,N-dimethyl-formamide	1.A A. A. Preparation of 2-[3-(trifluoromethyl)benzoyl]-hydrazinecarboxylic acid ethyl ester 70 g of (3-trifluoromethyl)benzoic acid hydrazide (0.34 mol) and 40 ml of pyridine were dissolved in 150 ml of N,N-dimethylformamide and stirred at 15° C. (water bath). 40 ml of ethyl chloroformate (0.41 mol) was added dropwise to this mixture while the reaction temperature was kept below 20° C. After addition of the ethylchloroformate, the resultant reaction mixture was stirred at room temperature for four hours and then 500 ml of water was added with stirring. The resultant precipitate was filtered by suction, washed with water four times, and then dried in air, to produce 80 g of 2-[3-(trifluoromethyl)benzoyl]hydrazinecarboxylic acid ethyl ester (85% yield). The structure was confirmed by infrared (IR) and nuclear magnetic resonance (NMR) spectra.
85%	With pyridine In water; N,N-dimethyl-formamide	1.A A. A. Preparation of 2-[3-(trifluoromethyl)benzoyl]-hydrazinecarboxylic acid ethyl ester 70 g of (3-trifluoromethyl)benzoic acid hydrazide (0.34 mol) and 40 ml of pyridine were dissolved in 150 ml of N,N-dimethylformamide and stirred at 15° C. (water bath). 40 ml of ethyl chloroformate (0.41 mol) was added dropwise to this mixture while the reaction temperature was kept below 20° C. After addition of the ethylchloro-formate, the resultant reaction mixture was stirred at room temperature for four hours and then 500 ml of water was added with stirring. The resultant precipitate was filtered by suction, washed with water four times, and then dried in air, to produce 80 g of 2-[3-(trifluoro-methyl)benzoyl]hydrazinecarboxylic acid ethyl ester (85% yield). The structure was confirmed by infrared (IR) and nuclear magnetic resonance (NMR) spectra.

Reference： [1]Current Patent Assignee: ELEMENT SOLUTIONS INC - US6011034, 2000, A
[2]Current Patent Assignee: ELEMENT SOLUTIONS INC - US6197766, 2001, B1

10
[ 2557-13-3 ]
[ 22227-25-4 ]

Yield	Reaction Conditions	Operation in experiment
83%	With hydrazine hydrate; In methanol; for 5h;Reflux;	General procedure: To a solution of an appropriate methyl esters17(a-j) (1.0 mmol) in 50 mL of methanol was added 99 %hydrazine hydrate (4.0 mmol) and the mixture was refluxedfor 5 h up to reaction completed (TLC). After completionof reaction, it was allowed to cool and the obtained solidwas washed with methanol. The crude products wererecrystallized from ethanol.
	With hydrazine hydrate; In methanol; at 65℃; for 4h;	General procedure: To a solution of esters (2a~2t, 1.0 equiv.), furan-2-carbonyl chloride (7a, 1.0 equiv.) orthiophene-2-carbonyl chloride (7b, 1.0 equiv.) in MeOH (2 mL/1 mmol) was added hydrazine hydrate(1 mL/1 mmol), then the mixture was allowed to reach 65 C and stirred for 4 h. After completion(monitored by TLC), the organic solvent was removed and extracted three times with ethyl acetate,the combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure to givethe corresponding hydrazides (3a~3t, 8a, or 8b) in high yields, which were taken up for the next stepwithout any purification.

Reference： [1]Medicinal Chemistry Research,2016,vol. 25,p. 627 - 643
[2]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 2909 - 2914
[3]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 6724 - 6731
[4]Patent: US9212151,2015,B2 .Location in patent: Page/Page column 93
[5]Molecules,2020,vol. 25

11
[ 22227-25-4 ]
[ 149-73-5 ]
[ 1450828-21-3 ]

Yield	Reaction Conditions	Operation in experiment
90%	With Al³⁺-K₁₀ montmorillonite clay In neat (no solvent) at 55℃; for 0.25h; Microwave irradiation;	General procedure for 1,3,4-oxadiazole synthesis General procedure: A 5 mL microwave vial was charged with acidhydrazide (100 mg, 1 eq), trimethyl orthoester (2 eq) and Al3+-K10 clay (75 mg). The resulting mixture was kept under microwave irradiation maintaining the temperature at 55 °C for 15 min (Microwave irradiations were performed on CEM-discover model No. 908010). The reaction was monitored by TLC. After completion of the reaction, reaction mixture was diluted with ethyl acetate stirred well, filtered, washed well with ethyl acetate. Filtrate was evaporated under reduced pressure to obtain highly pure product. In some cases, products were purified by column chromatography using 60-120 mesh silica with 20-100 % ethyl acetate in pet ether as eluting solvents. The catalyst recovered by filtration was reused for another 5 more times.

Reference： [1]Suresh, Dhanusu; Kanagaraj, Kuppusamy; Pitchumani, Kasi [Tetrahedron Letters, 2014, vol. 55, # 27, p. 3678 - 3682]
[2]Palmer, James T.; Hirschbein, Bernard L.; Cheung, Harry; McCarter, John; Janc, James W.; Yu, Z. Walter; Wesolowski, Gregg [Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 11, p. 2909 - 2914]

12
[ 698-63-5 ]
[ 22227-25-4 ]
C₁₃H₈F₃N₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	In ethanol; water Heating;

Reference： [1]Rando, Daniela G.; Avery, Mitchell A.; Tekwani, Babu L.; Khan, Shabana I.; Ferreira, Elizabeth I. [Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 14, p. 6724 - 6731]

13
[ 4521-33-9 ]
[ 22227-25-4 ]
C₁₃H₈F₃N₃O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	In ethanol; water Heating;

Reference： [1]Rando, Daniela G.; Avery, Mitchell A.; Tekwani, Babu L.; Khan, Shabana I.; Ferreira, Elizabeth I. [Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 14, p. 6724 - 6731]

14
[ 2131-62-6 ]
[ 22227-25-4 ]
[ 1073613-02-1 ]

Yield	Reaction Conditions	Operation in experiment
84%	In tetrahydrofuran for 2h; Reflux;	12 Example 12General Synthesis Schemes 2-4; Synthesis Scheme 2 describes synthesis of compounds that instead of a thiazolidinone group as Ring B (see FIG. 1), have a thiazole, thiadiazole, or 1,2,3-triazole group. See also Table 2. Thiadiazole synthesis is performed by methods known in the art, for example, Oruc et al., J. Med. Chem. 47:6760-67 (2004). As shown in Scheme 2, thiazole analogs 59 and 60 were synthesized by bromination of acetophenone 57 in acetic acid at 0° C. for 2 h, followed by reaction with substituted phenylthiourea in refluxing ethanol.Synthesis of thiadiazole compounds 64 and 65 proceeded as shown in Scheme 3 and as outlined below.Synthesis of compound 62: 3-Trifluoromethyl benzoic Acid Hydrazide 60b: Hydrazine hydrate (4 equivalent) was added to the stirred solution of 3-trifluoromethyl benzoyl chloride 60 in pyridine at 0° C. Reaction mixture was added to the ice cold water and precipitate was collected and recrystallized from ethanol.Thiosemicarbazides 61. Mixture of above hydrazide 60b (1 g, 5 mmol) and appropriate carboxyphenylisothiocyanate (5 mmol) in THF was refluxed for 2 hrs. Solid, obtained after solvent evaporation, was purified by recrystallization from ethanol to afford thiosemicarbazide 61 (yield 74-84%).4-[(5-(3-Trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl)amino]-benzoic acid (Compound 62). Thiosemicarbazide 61 (2.6 mmol) was added portion wise to 10 ml of concentrated sulfuric acid; stirred for 30 min at room temperature and reaction content was slowly dumped into stirring ice-water mixture. The precipitated product was purified by flash chromatography to yield (77%) of final product, 62. 1H NMR (DMSO-d6): δ10.985 (bs, 1H, COOH), 8.136-8.112 (m, 3H, trifluoromethylphenyl), 7.904 (d, 2H, J=8.301 Hz, carboxyphenyl) 7.845-7.712 (m, 5H, carboxyphenyl and trifluoromethylphenyl, NH); MS (ES+) (m/z): [M+1]+ calculated for C16H10F3N3O2S, 366.35. found 366.46.Scheme 4 shows the synthesis of 1,2,3-triazoles. 1,3-Dipolar cycloaddition of alkynes 66 and 67 with 4-azidobenzoic acid produced the 1,2,3-triazoles (compounds 68 and 69) in high yields. Single spot in TLC indicated that adducts were predominantly 4-regioisomers.Scheme 5 shows synthesis of compounds 49 and 50. Briefly, maleimide intermediates 4 (R4=Cl or H) were prepared by reaction of 3-trifluoromethylaniline with dichloromaleic anhydride (R4=Cl) or maleic anhydride (R4=H) in refluxing acetic anhydride (Scheme 2). Subsequent reaction with 4-aminobenzoic acid and 4-mercaptobenzoic acid produced compounds 49 and 50 (dotted line indicates double bond in 49).
74%	In tetrahydrofuran for 2h; Reflux;

Reference： [1]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - US2011/105565, 2011, A1 Location in patent: Page/Page column 30-31
[2]Location in patent: experimental part Sonawane; Verkman [Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 17, p. 8187 - 8195]

15
[ 2251-65-2 ]
[ 22227-25-4 ]

Yield	Reaction Conditions	Operation in experiment
83%	With pyridine; hydrazine at 0℃;
76%	Stage #1: 3-(Trifluoromethyl)benzoyl chloride With triethylamine In methanol at 20℃; Sealed tube; Stage #2: With hydrazine hydrate monohydrate In water monomer at 120℃; for 5h;
66%	With hydrazine hydrate monohydrate In ethanol Reflux;

	With pyridine; hydrazine hydrate monohydrate at 0℃;	12 Example 12General Synthesis Schemes 2-4; Synthesis Scheme 2 describes synthesis of compounds that instead of a thiazolidinone group as Ring B (see FIG. 1), have a thiazole, thiadiazole, or 1,2,3-triazole group. See also Table 2. Thiadiazole synthesis is performed by methods known in the art, for example, Oruc et al., J. Med. Chem. 47:6760-67 (2004). As shown in Scheme 2, thiazole analogs 59 and 60 were synthesized by bromination of acetophenone 57 in acetic acid at 0° C. for 2 h, followed by reaction with substituted phenylthiourea in refluxing ethanol.Synthesis of thiadiazole compounds 64 and 65 proceeded as shown in Scheme 3 and as outlined below.Synthesis of compound 62: 3-Trifluoromethyl benzoic Acid Hydrazide 60b: Hydrazine hydrate (4 equivalent) was added to the stirred solution of 3-trifluoromethyl benzoyl chloride 60 in pyridine at 0° C. Reaction mixture was added to the ice cold water and precipitate was collected and recrystallized from ethanol.Thiosemicarbazides 61. Mixture of above hydrazide 60b (1 g, 5 mmol) and appropriate carboxyphenylisothiocyanate (5 mmol) in THF was refluxed for 2 hrs. Solid, obtained after solvent evaporation, was purified by recrystallization from ethanol to afford thiosemicarbazide 61 (yield 74-84%).4-[(5-(3-Trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl)amino]-benzoic acid (Compound 62). Thiosemicarbazide 61 (2.6 mmol) was added portion wise to 10 ml of concentrated sulfuric acid; stirred for 30 min at room temperature and reaction content was slowly dumped into stirring ice-water mixture. The precipitated product was purified by flash chromatography to yield (77%) of final product, 62. 1H NMR (DMSO-d6): δ10.985 (bs, 1H, COOH), 8.136-8.112 (m, 3H, trifluoromethylphenyl), 7.904 (d, 2H, J=8.301 Hz, carboxyphenyl) 7.845-7.712 (m, 5H, carboxyphenyl and trifluoromethylphenyl, NH); MS (ES+) (m/z): [M+1]+ calculated for C16H10F3N3O2S, 366.35. found 366.46.Scheme 4 shows the synthesis of 1,2,3-triazoles. 1,3-Dipolar cycloaddition of alkynes 66 and 67 with 4-azidobenzoic acid produced the 1,2,3-triazoles (compounds 68 and 69) in high yields. Single spot in TLC indicated that adducts were predominantly 4-regioisomers.Scheme 5 shows synthesis of compounds 49 and 50. Briefly, maleimide intermediates 4 (R4=Cl or H) were prepared by reaction of 3-trifluoromethylaniline with dichloromaleic anhydride (R4=Cl) or maleic anhydride (R4=H) in refluxing acetic anhydride (Scheme 2). Subsequent reaction with 4-aminobenzoic acid and 4-mercaptobenzoic acid produced compounds 49 and 50 (dotted line indicates double bond in 49).
	Multi-step reaction with 2 steps 1: sodium hydroxide 2: hydrazine hydrate monohydrate
	Multi-step reaction with 2 steps 1: sulfuric acid / 5 h / 60 °C 2: hydrazine hydrate monohydrate / 12 h / 80 °C
	Multi-step reaction with 2 steps 1: sodium hydroxide 2: hydrazine monohydrate / methanol / 0.5 h / Reflux

Reference： [1]Location in patent: experimental part Sonawane; Verkman [Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 17, p. 8187 - 8195]
[2]Zender, Michael; Klein, Tobias; Henn, Claudia; Kirsch, Benjamin; Maurer, Christine K.; Kail, Dagmar; Ritter, Christiane; Dolezal, Olan; Steinbach, Anke; Hartmann, Rolf W. [Journal of Medicinal Chemistry, 2013, vol. 56, # 17, p. 6761 - 6774]
[3]Zhu, Weixing; Haupenthal, Jörgm; Groh, Matthias; Fountain, Michelle; Hartmann, Rolf W. [Antimicrobial Agents and Chemotherapy, 2014, vol. 58, # 7, p. 4242 - 4245]
[4]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - US2011/105565, 2011, A1 Location in patent: Page/Page column 30-31
[5]Öztürk, Mehmet; Demirtaş, Ibrahim; Iyidoğan, Ayşegül Karaküçük; Kurşun Aktar, Bedriye Seda; Oruç-Emre, Emine Elçin; Sıcak, Yusuf; Tok, Tuğba Taşkın; Yağlıoğlu, Ayse Şahin [Journal of Molecular Structure, 2020, vol. 1211]
[6]Bai, Hangyu; Jiang, Weiqi; Li, Qi; Li, Tian; Ma, Shichuang; Shi, Baojun; Wu, Wenjun [Journal of Agricultural and Food Chemistry, 2021, vol. 69, # 39, p. 11572 - 11581]
[7]Kurşun Aktar, Bedriye Seda; Sicak, Yusuf; Tatar, Gizem; Oruç-Emre, Emine Elçin [Turkish Journal of Chemistry, 2022, vol. 46, # 1, p. 236 - 252]

16
[ 22227-25-4 ]
[ 1073613-03-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: tetrahydrofuran / 2 h / Reflux 2: sulfuric acid / 0.5 h / 20 °C

Reference： [1]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - US2011/105565, 2011, A1

17
[ 1313803-53-0 ]
[ 22227-25-4 ]
C₂₂H₁₈F₃N₅O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In ethanol at 60℃; for 1h;

Reference： [1]Location in patent: scheme or table Li, Wei; Zhai, Xin; Ding, Lu; Sun, Limin; Chen, Xiaomei; Gong, Ping; Sun, Tiemin [Molecules, 2011, vol. 16, # 6, p. 5130 - 5141]

18
[ 14036-06-7 ]
[ 22227-25-4 ]
[ 1340587-14-5 ]

Yield	Reaction Conditions	Operation in experiment
91%	In acetonitrile at 20℃; for 0.166667h;	4.1.1. General procedure for the synthesis of ethyl benzoylhydrazonoformate 2a-2e (for the atom numbering scheme for ¹H NMR spectra assignment, see Fig. 2) General procedure: Diethoxymethyl acetate (243 mg, 1.5 mmol) was added at room temperature to the mixture of a substituted benzoic acid hydrazide 1 (1 mmol) in acetonitrile (10 mL). Reaction mixture was then stirred for 10 min at room temperature and evaporated to dryness. A crude product was recrystallized from the appropriate solvent.

Reference： [1]Location in patent: experimental part Vavříková, Eva; Polanc, Slovenko; Kočevar, Marijan; Horváti, Kata; Bsze, Szilvia; Stolaříková, Jiřina; Vávrová, Kateřina; Vinšová, Jarmila [European Journal of Medicinal Chemistry, 2011, vol. 46, # 10, p. 4937 - 4945]

19
[ 22227-25-4 ]
[ 1340587-04-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: acetonitrile / 0.17 h / 20 °C 2: acetic acid / acetonitrile / 4.5 h / 20 - 50 °C

Reference： [1]Vavříková, Eva; Polanc, Slovenko; Kočevar, Marijan; Horváti, Kata; Bsze, Szilvia; Stolaříková, Jiřina; Vávrová, Kateřina; Vinšová, Jarmila [European Journal of Medicinal Chemistry, 2011, vol. 46, # 10, p. 4937 - 4945]

20
[ 22227-25-4 ]
[ 502686-01-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydroxide / 72 h / 20 °C 2: water / 180 °C / Microwave irradiation

Reference： [1]Bera, Hriday; Tan, Bee Jen; Sun, Lingyi; Dolzhenko, Anton V.; Chui, Wai-Keung; Chiu, Gigi Nagar Chee [European Journal of Medicinal Chemistry, 2013, vol. 67, p. 325 - 334]

21
[ 22227-25-4 ]
[ 1456614-02-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: sodium hydroxide / 72 h / 20 °C 2: water / 180 °C / Microwave irradiation 3: N,N-dimethyl-formamide / 5 h / 20 °C

Reference： [1]Bera, Hriday; Tan, Bee Jen; Sun, Lingyi; Dolzhenko, Anton V.; Chui, Wai-Keung; Chiu, Gigi Nagar Chee [European Journal of Medicinal Chemistry, 2013, vol. 67, p. 325 - 334]

22
[ 22227-25-4 ]
[ 1456613-74-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: sodium hydroxide / 72 h / 20 °C 2: water / 180 °C / Microwave irradiation 3: N,N-dimethyl-formamide / 5 h / 20 °C 4: sodium hydroxide / ethanol; water / 0.33 h / 100 °C

Reference： [1]Bera, Hriday; Tan, Bee Jen; Sun, Lingyi; Dolzhenko, Anton V.; Chui, Wai-Keung; Chiu, Gigi Nagar Chee [European Journal of Medicinal Chemistry, 2013, vol. 67, p. 325 - 334]

23
[ 14527-26-5 ]
[ 22227-25-4 ]
C₉H₉F₃N₄O [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 67,p. 325 - 334

24
[ 22227-25-4 ]
[ 1432053-94-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 1.5 h / 0 °C / Inert atmosphere 2: p-toluenesulfonyl chloride / dichloromethane / 12 h / 20 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: potassium carbonate / dichloromethane / 0 - 20 °C 2: triethylamine; p-toluenesulfonyl chloride / dichloromethane / 2 h / 0 - 20 °C

Reference： [1]Zender, Michael; Klein, Tobias; Henn, Claudia; Kirsch, Benjamin; Maurer, Christine K.; Kail, Dagmar; Ritter, Christiane; Dolezal, Olan; Steinbach, Anke; Hartmann, Rolf W. [Journal of Medicinal Chemistry, 2013, vol. 56, # 17, p. 6761 - 6774]
[2]Current Patent Assignee: MISSION THERAPEUTICS LIMITED - WO2021/239863, 2021, A1

25
[ 22227-25-4 ]
[ 1450828-22-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydrogencarbonate / water; 1,4-dioxane / 1 h / 0 °C 2: Burgess Reagent / tetrahydrofuran / 0.03 h / 150 °C / Microwave irradiation; Inert atmosphere

Reference： [1]Zender, Michael; Klein, Tobias; Henn, Claudia; Kirsch, Benjamin; Maurer, Christine K.; Kail, Dagmar; Ritter, Christiane; Dolezal, Olan; Steinbach, Anke; Hartmann, Rolf W. [Journal of Medicinal Chemistry, 2013, vol. 56, # 17, p. 6761 - 6774]

26
[ 22227-25-4 ]
[ 1450828-23-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 24 h / 0 - 20 °C 2: Burgess Reagent / tetrahydrofuran / 0.03 h / 150 °C / Microwave irradiation; Inert atmosphere

Reference： [1]Zender, Michael; Klein, Tobias; Henn, Claudia; Kirsch, Benjamin; Maurer, Christine K.; Kail, Dagmar; Ritter, Christiane; Dolezal, Olan; Steinbach, Anke; Hartmann, Rolf W. [Journal of Medicinal Chemistry, 2013, vol. 56, # 17, p. 6761 - 6774]

27
[ 22227-25-4 ]
[ 1477520-15-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 1.5 h / 0 °C / Inert atmosphere 2: p-toluenesulfonyl chloride / dichloromethane / 12 h / 20 °C / Inert atmosphere 3: ammonia; methanol / diethyl ether / 48 h / 20 °C / Sealed tube

Reference： [1]Zender, Michael; Klein, Tobias; Henn, Claudia; Kirsch, Benjamin; Maurer, Christine K.; Kail, Dagmar; Ritter, Christiane; Dolezal, Olan; Steinbach, Anke; Hartmann, Rolf W. [Journal of Medicinal Chemistry, 2013, vol. 56, # 17, p. 6761 - 6774]

28
[ 22227-25-4 ]
[ 79-22-1 ]
[ 1450828-19-9 ]

Yield	Reaction Conditions	Operation in experiment
93%	With sodium hydrogencarbonate In 1,4-dioxane; water at 0℃; for 1h;

Reference： [1]Zender, Michael; Klein, Tobias; Henn, Claudia; Kirsch, Benjamin; Maurer, Christine K.; Kail, Dagmar; Ritter, Christiane; Dolezal, Olan; Steinbach, Anke; Hartmann, Rolf W. [Journal of Medicinal Chemistry, 2013, vol. 56, # 17, p. 6761 - 6774]

29
[ 22227-25-4 ]
[ 407-25-0 ]
[ 1450828-20-2 ]

Yield	Reaction Conditions	Operation in experiment
44%	With triethylamine In dichloromethane at 0 - 20℃; for 24h;

Reference： [1]Zender, Michael; Klein, Tobias; Henn, Claudia; Kirsch, Benjamin; Maurer, Christine K.; Kail, Dagmar; Ritter, Christiane; Dolezal, Olan; Steinbach, Anke; Hartmann, Rolf W. [Journal of Medicinal Chemistry, 2013, vol. 56, # 17, p. 6761 - 6774]

30
[ 22227-25-4 ]
[ 4755-77-5 ]
ethyl 2-oxo-2-(2-(3-(trifluoromethyl)benzoyl)hydrazineyl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate In dichloromethane at 0 - 20℃;	ii Step (ii) Ethyl 2-oxo-2-(2-(3-(trifluoromethyl)benzoyl)hydrazineyl)acetate To a stirred solution of 3-(trifluoromethyl)benzohydrazide (3.4 g, 16.66 mmol) in DCM (40 mL) was added K2CO3 (6.89 g, 49.98 mmol) at rt. Ethyl oxalyl chloride (3.41 g, 2.79 mL, 24.99 mmol) was added dropwise at 0 °C. The mixture was allowed to warm to rt, stirred for 2 h, then poured into water (500 mL) and extracted with EtOAc (2 x 400 mL). The combined organic phases were dried over Na2SO4 and concentrated under reduced pressure to afford ethyl 2-oxo-2-(2-(3-(trifluoromethyl)benzoyl)hydrazineyl)acetate (6.0 g, quantitative yield). LCMS: Method C, 1.43 min, MS: ES+ 305.0.
	With triethylamine In dichloromethane at 0℃; for 1.5h; Inert atmosphere;

Reference： [1]Current Patent Assignee: MISSION THERAPEUTICS LIMITED - WO2021/239863, 2021, A1 Location in patent: Page/Page column 41
[2]Zender, Michael; Klein, Tobias; Henn, Claudia; Kirsch, Benjamin; Maurer, Christine K.; Kail, Dagmar; Ritter, Christiane; Dolezal, Olan; Steinbach, Anke; Hartmann, Rolf W. [Journal of Medicinal Chemistry, 2013, vol. 56, # 17, p. 6761 - 6774]

31
[ 22227-25-4 ]
[ 122-51-0 ]
[ 1450828-21-3 ]

Yield	Reaction Conditions	Operation in experiment
62%	at 160℃; for 2h; Sealed tube; Inert atmosphere;

Reference： [1]Zender, Michael; Klein, Tobias; Henn, Claudia; Kirsch, Benjamin; Maurer, Christine K.; Kail, Dagmar; Ritter, Christiane; Dolezal, Olan; Steinbach, Anke; Hartmann, Rolf W. [Journal of Medicinal Chemistry, 2013, vol. 56, # 17, p. 6761 - 6774]

32
[ 22227-25-4 ]
[ 78-39-7 ]
[ 1340964-71-7 ]

Yield	Reaction Conditions	Operation in experiment
41%	at 150℃; Sealed tube;

Reference： [1]Zender, Michael; Klein, Tobias; Henn, Claudia; Kirsch, Benjamin; Maurer, Christine K.; Kail, Dagmar; Ritter, Christiane; Dolezal, Olan; Steinbach, Anke; Hartmann, Rolf W. [Journal of Medicinal Chemistry, 2013, vol. 56, # 17, p. 6761 - 6774]

33
[ 22227-25-4 ]
[ 530-62-1 ]
[ 1334627-21-2 ]

Yield	Reaction Conditions	Operation in experiment
37%	With triethylamine In dichloromethane at 20℃; for 0.5h;

Reference： [1]Zender, Michael; Klein, Tobias; Henn, Claudia; Kirsch, Benjamin; Maurer, Christine K.; Kail, Dagmar; Ritter, Christiane; Dolezal, Olan; Steinbach, Anke; Hartmann, Rolf W. [Journal of Medicinal Chemistry, 2013, vol. 56, # 17, p. 6761 - 6774]

34
[ 22227-25-4 ]
[ 103-72-0 ]
N-phenyl-2-(3-(trifluoromethyl)benzoyl)hydrazinecarbothioamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46%	In ethanol for 2h; Reflux;

Reference： [1]Zhu, Weixing; Haupenthal, Jörgm; Groh, Matthias; Fountain, Michelle; Hartmann, Rolf W. [Antimicrobial Agents and Chemotherapy, 2014, vol. 58, # 7, p. 4242 - 4245]

35
[ 22227-25-4 ]
[ 286009-79-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: ethanol / 2 h / Reflux 2: sodium hydroxide / water / 2 h / Reflux; Heating

Reference： [1]Zhu, Weixing; Haupenthal, Jörgm; Groh, Matthias; Fountain, Michelle; Hartmann, Rolf W. [Antimicrobial Agents and Chemotherapy, 2014, vol. 58, # 7, p. 4242 - 4245]

36
[ 1445-45-0 ]
[ 22227-25-4 ]
[ 1340964-71-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	With Al³⁺-K₁₀ montmorillonite clay In neat (no solvent) at 55℃; for 0.25h; Microwave irradiation;	General procedure for 1,3,4-oxadiazole synthesis General procedure: A 5 mL microwave vial was charged with acidhydrazide (100 mg, 1 eq), trimethyl orthoester (2 eq) and Al3+-K10 clay (75 mg). The resulting mixture was kept under microwave irradiation maintaining the temperature at 55 °C for 15 min (Microwave irradiations were performed on CEM-discover model No. 908010). The reaction was monitored by TLC. After completion of the reaction, reaction mixture was diluted with ethyl acetate stirred well, filtered, washed well with ethyl acetate. Filtrate was evaporated under reduced pressure to obtain highly pure product. In some cases, products were purified by column chromatography using 60-120 mesh silica with 20-100 % ethyl acetate in pet ether as eluting solvents. The catalyst recovered by filtration was reused for another 5 more times.

Reference： [1]Suresh, Dhanusu; Kanagaraj, Kuppusamy; Pitchumani, Kasi [Tetrahedron Letters, 2014, vol. 55, # 27, p. 3678 - 3682]

37
[ 13037-60-0 ]
[ 22227-25-4 ]
C₁₅H₉BrF₃N₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate In water at 90℃; for 2h; Green chemistry;

Reference： [1]Wen, Li-Rong; Li, Shou-Lei; Zhang, Jian; Li, Ming [Green Chemistry, 2015, vol. 17, # 3, p. 1581 - 1588]

38
[ 27806-85-5 ]
[ 22227-25-4 ]
C₁₆H₁₃F₃N₄O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In pyridine at 90 - 100℃;

Reference： [1]Current Patent Assignee: AMITECH THERAPEUTIC SOLUTIONS - US9212151, 2015, B2 Location in patent: Page/Page column 94

39
[ 75-15-0 ]
[ 22227-25-4 ]
5-(3-(trifluoromethyl)phenyl)-1,3,4-oxadiazole-2-thione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium hydroxide In ethanol Reflux;	General procedure for the preparation of 1,3,4-oxadiazole-2-thiones (19a-j) General procedure: Acid hydrazides 18(a-j) (1.0 mmol)were dissolved in ethanol (50 mL),and to this potassiumhydroxide was added (1.49 mmol) which is dissolved inwater (2 mL), and then carbondisulfide was added(4.0 mmol). Then, the reaction mixture was heated at reflux for 10-12 h. Solvent was evaporated, and the residue wasacidified with 10 % HCl. The precipitate was collected byfiltration, washed with water and dried. The products 19(a-j) were used without further purification.
	With potassium hydroxide In ethanol at 85℃; for 3h;
	With potassium hydroxide In ethanol at 85℃; for 3h;	- Route B (R1 = aryl) General procedure: Note: hydrazine and carbon disulphide used during this procedure have to be handled withcaution.The carboxylic compound was first converted into its ethyl ester by refluxing in absoluteethanol in the presence of a few drops of H2SO4. The ester was then treated overnight withhydrazine hydrate (2 to 4 equiv.) without solvent at 120 °C. Evaporation of excess hydrazineyielded the corresponding hydrazide compound. The hydrazide, solubilized in absolute ethanol,was treated with CS2 (5 equiv.) in the presence of KOH (1.7 equiv.) at 85 °C for 3 h. Water wasadded and pH was adjusted to 2-3 with 1N HCl. The formed precipitate was collected byfiltration and washed with water, yielding the 1,3,4-oxadiazol-thione, which was used withoutfurther purification. Finally, the preceding compound was treated with hydrazine hydrate (10equiv.) in absolute ethanol at 100 °C overnight in a sealed tube. After evaporation of excesshydrazine, the residue was purified on a silica gel column to yield the final compound.

Reference： [1]Murty; Penthala, Raju; Polepalli, Sowjanya; Jain [Medicinal Chemistry Research, 2016, vol. 25, # 4, p. 627 - 643]
[2]Sevaille, Laurent; Gavara, Laurent; Bebrone, Carine; De Luca, Filomena; Nauton, Lionel; Achard, Maud; Mercuri, Paola; Tanfoni, Silvia; Borgianni, Luisa; Guyon, Carole; Lonjon, Pauline; Turan-Zitouni, Gülhan; Dzieciolowski, Julia; Becker, Katja; Bénard, Lionel; Condon, Ciaran; Maillard, Ludovic; Martinez, Jean; Frère, Jean-Marie; Dideberg, Otto; Galleni, Moreno; Docquier, Jean-Denis; Hernandez, Jean-François [ChemMedChem, 2017, vol. 12, # 12, p. 972 - 985]
[3]Baud, Damien; Bebrone, Carine; Becker, Katja; Benvenuti, Manuela; Cerboni, Giulia; Chelini, Giulia; Cutolo, Giuliano; De Luca, Filomena; Docquier, Jean-Denis; Feller, Georges; Fischer, Marina; Galleni, Moreno; Gavara, Laurent; Gresh, Nohad; Kwapien, Karolina; Legru, Alice; Mangani, Stefano; Mercuri, Paola; Pozzi, Cecilia; Sannio, Filomena; Sevaille, Laurent; Tanfoni, Silvia; Verdirosa, Federica; Berthomieu, Dorothée; Bestgen, Benoît; Frère, Jean-Marie; Hernandez, Jean-François [European Journal of Medicinal Chemistry, 2020, vol. 208]

40
[ 454-92-2 ]
[ 22227-25-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sulfuric acid / 6 h / Reflux 2: hydrazine hydrate / methanol / 5 h / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate / neat (no solvent) / 120 °C / Sealed tube
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate / Reflux

	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate / ethanol / Reflux
	Multi-step reaction with 2 steps 1: thionyl chloride / 1 h / 40 °C 2: hydrazine hydrate / methanol / 4 h / 65 °C
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate / neat (no solvent) / 120 °C / Sealed tube
	Multi-step reaction with 2 steps 1: sulfuric acid / 5 h / Reflux 2: hydrazine hydrate / ethanol / 100 °C / Sealed tube

Reference： [1]Murty; Penthala, Raju; Polepalli, Sowjanya; Jain [Medicinal Chemistry Research, 2016, vol. 25, # 4, p. 627 - 643]
[2]Sevaille, Laurent; Gavara, Laurent; Bebrone, Carine; De Luca, Filomena; Nauton, Lionel; Achard, Maud; Mercuri, Paola; Tanfoni, Silvia; Borgianni, Luisa; Guyon, Carole; Lonjon, Pauline; Turan-Zitouni, Gülhan; Dzieciolowski, Julia; Becker, Katja; Bénard, Lionel; Condon, Ciaran; Maillard, Ludovic; Martinez, Jean; Frère, Jean-Marie; Dideberg, Otto; Galleni, Moreno; Docquier, Jean-Denis; Hernandez, Jean-François [ChemMedChem, 2017, vol. 12, # 12, p. 972 - 985]
[3]Xu; Wang; Luo; Yu; Guo; Fu; Zhao; Wu [RSC Advances, 2018, vol. 8, # 12, p. 6306 - 6314]
[4]Yu, Gang; Chen, Shunhong; He, Feng; Luo, Dexia; Zhang, Yu; Wu, Jian [Turkish Journal of Chemistry, 2019, vol. 43, # 4, p. 1075 - 1085]
[5]Yuan, Chen; Yan, Jie; Song, Chen; Yang, Fan; Li, Chao; Wang, Cheng; Su, Huiling; Chen, Wei; Wang, Lijiao; Wang, Zhouyu; Qian, Shan; Yang, Lingling [Molecules, 2020, vol. 25, # 1]
[6]Baud, Damien; Bebrone, Carine; Becker, Katja; Benvenuti, Manuela; Cerboni, Giulia; Chelini, Giulia; Cutolo, Giuliano; De Luca, Filomena; Docquier, Jean-Denis; Feller, Georges; Fischer, Marina; Galleni, Moreno; Gavara, Laurent; Gresh, Nohad; Kwapien, Karolina; Legru, Alice; Mangani, Stefano; Mercuri, Paola; Pozzi, Cecilia; Sannio, Filomena; Sevaille, Laurent; Tanfoni, Silvia; Verdirosa, Federica; Berthomieu, Dorothée; Bestgen, Benoît; Frère, Jean-Marie; Hernandez, Jean-François [European Journal of Medicinal Chemistry, 2020, vol. 208]
[7]Gavara, Laurent; Legru, Alice; Verdirosa, Federica; Sevaille, Laurent; Nauton, Lionel; Corsica, Giuseppina; Mercuri, Paola Sandra; Sannio, Filomena; Feller, Georges; Coulon, Rémi; De Luca, Filomena; Cerboni, Giulia; Tanfoni, Silvia; Chelini, Giulia; Galleni, Moreno; Docquier, Jean-Denis; Hernandez, Jean-François [Bioorganic Chemistry, 2021, vol. 113]

41
[ 22227-25-4 ]
(E)-N-(4'-(3,5-dimethoxystyryl)phenyl)-2-((5-(3''-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2-yl)thio)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium hydroxide / ethanol / Reflux 2: potassium carbonate / acetonitrile / 20 °C

Reference： [1]Murty; Penthala, Raju; Polepalli, Sowjanya; Jain [Medicinal Chemistry Research, 2016, vol. 25, # 4, p. 627 - 643]

42
[ 22227-25-4 ]
(E)-4'-(3,5-dimethoxystyryl)phenyl 2-((5-(3''-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2-yl)thio)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium hydroxide / ethanol / Reflux 2: potassium carbonate / acetonitrile / 20 °C

Reference： [1]Murty; Penthala, Raju; Polepalli, Sowjanya; Jain [Medicinal Chemistry Research, 2016, vol. 25, # 4, p. 627 - 643]

43
7-[1-(tert-butoxycarbonyl)piperidin-4-yl]-5-oxo-4,5-dihydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid [ No CAS ]
[ 22227-25-4 ]
tert-butyl 4-[5-oxo-3-({2-[3-(trifluoromethyl)benzoyl]hydrazino}carbonyl)-4,5-dihydropyrazolo[1,5-a]pyrimidin-7-yl]piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 16h;	200A Example 200A tert-butyl 4-[5-oxo-3-({2-[3-(trifluoromethyl)benzoyl]hydrazino}carbonyl)-4,5-dihydropyrazolo[l,5- a]pyrimidin-7-yl]piperidine- 1 -carbox late 7-[l-(te^butoxycarbonyl)piperidin-4-yl]-5-oxo-4,5-dihydropyrazolo[l,5-a]pyrimidine-3-carboxylic acid (150 mg, 0.42 mmol) and 3-(trifluoromethyl)benzohydrazide (126 mg, 0.62 mmol) were dissolved in N,N-Dimethylformamide (1,5 ml). N,N-Diisopropylethylamin (0.22 ml, 1.24 mmol) and N- [(Dimethylamino)(3H-[l,2,3]triazolo[4,5-b]pyridin-3-yloxy)methyliden]-N-methyl-methanaminium- hexafluorophosphate (266 mg, 0.62 mmol) were added and the mixture was stirred for 16h at RT. The mixture was purified via reverse phase HPLC (gradient acetonitrile/water with 0.01 % trifluoroacetic acid) which afforded the title compound (154 mg, 68% of theory). LC-MS (Method 5B): Rt = 0.93 min, MS (ESIPos): m z = 549.5 [M+H]+

Reference： [1]Current Patent Assignee: BAYER AG - WO2016/71216, 2016, A1 Location in patent: Page/Page column 255

44
4-propyl-1,2,3-thiadiazol-5-carbaldehyde [ No CAS ]
[ 22227-25-4 ]
C₁₄H₁₃F₃N₄OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With acetic acid In ethanol at 20℃; for 4h;	4 Example 4: 4-propyl-5-carbaldehyde _1,2,3_ thiadiazol-3-trifluoromethyl - benzoyl hydrazone (I-31) Preparation To a 50 ml flask is added in three 20 ml ethanol and 0.47g (3mmol) a compound represented by the formula II 4-propyl -1, 2, 3-thiadiazol-5-formaldehyde, stirring, disposable by adding 0.6 mg (0.01mmol) acetic acid to activate, then the 0.62g (3mmol) a compound represented by the formula III (R2to 3 substituted trifluoromethyl) 3-trifluoromethyl-benzoyl [...] ethanol, is slowly added in the above-mentioned three-mouth flask, condensation reaction at room temperature 4 hours later, to stop the reaction. Placed the reaction liquid refrigerator sleepovers, filtering, drying filter cake to get the yellow solid 0.81g, yield 79%.

Reference： [1]Current Patent Assignee: CHINA AGRICULTURAL UNIVERSITY - CN105439979, 2016, A Location in patent: Paragraph 0049; 0050; 0055

45
1-[4-hydroxy-3-(2-methyl-benzofuran-5-yl)phenyl]-2-propanone [ No CAS ]
[ 22227-25-4 ]
1-[4-hydroxy-3-(2-methylbenzofuran-5-yl)phenyl]-2-propanone 3-trifluoromethylbenzoylhydrazone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With acetic acid In ethanol for 5h; Reflux;	General procedure for the synthesis of substitutedbenzoylhydrazone (7-23) General procedure: To a solution of 5 (0.5 mmol) and substituted benzoylhydrazide (0.55 mmol) in EtOH(20 ml) acetic acid (0.2 ml) was added. After stirred and refluxed for 5 h, the reactionwas concentrated, poured into saturated salt water, shocked, and placed until precipitation.Then the precipitate was separated by filtration, washed with water, and driedto afford substituted benzoylhydrazone (7-23).
85.8%	With acetic acid In ethanol at 20℃; for 4h;	3 Example 3 1- [4-hydroxy-3- (2-methyl-benzofuran-5-yl) phenyl] -2-propanone -3-trifluoromethyl-benzoyl hydrazone 0.5mmol1- [4- hydroxy-3- (2-methyl-benzofuran-5-yl) phenyl] -2-propanone, 0.55mmol3- trifluoromethylbenzoyl hydrazine, dissolved with 20ml of ethanol was added 0.2 ml glacial acetic acid, stirred at room temperature after 4h, add 50ml ethanol distilled under reduced pressure to a residual solution 5ml, TLC monitoring completion of the reaction; adding water, fully shock, standing, the precipitated solid was filtered, the filter cake washed with water and washed with 50% ethanol, dried a pale yellow solid 1- [4-hydroxy-3- (2-methyl-benzofuran-5-yl) phenyl] -2-propanone 3-trifluoromethyl-benzoyl hydrazone, yield 85.8%

Reference： [1]Lin, Ding; Yi, Yang-Jie; Xiao, Meng-Wu; Chen, Jia; Ye, Jiao; Hu, Ai-Xi; Lian, Wen-Wen; Liu, Ai-Lin; Du, Guan-Hua [Journal of Asian Natural Products Research, 2019, vol. 21, # 11, p. 1052 - 1067]
[2]Current Patent Assignee: HUNAN UNIVERSITY - CN105693665, 2016, A Location in patent: Paragraph 0050; 0051; 0052; 0053

46
[ 22227-25-4 ]
[ 84782-51-4 ]
C₁₇H₁₅F₃N₂OSe [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid In ethanol for 2h; Reflux; Inert atmosphere;	6.1 1) Equivalent amounts of α-phenylselenopropanal (0.213 g, 1 mmol) and trimethylphenylhydrazine V-6 (1 mmol, 0.167 g) were added to a round bottom flask containing 20 mL of ethanol. It was stirred to completely dissolve. 800 μL of acetic acid was then added. The reaction was refluxed under nitrogen for 2 h. After TLC detection reaction was complete. The subsequent treatment was carried out as in Example 1, Step 1 to obtain a phenylseleno group-containing intermediate (III-6).

Reference： [1]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - CN104016938, 2016, B Location in patent: Paragraph 0059

47
1-(1-phenylcyclopropanecarbonyl)piperidin-4-one [ No CAS ]
[ 22227-25-4 ]
C₂₃H₂₄F₃N₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-(1-phenylcyclopropanecarbonyl)piperidin-4-one; 3-(trifluoromethyl)benzene-1-carbohydrazide In methanol at 30 - 50℃; for 3h; Inert atmosphere; Stage #2: With sodium tetrahydroborate In methanol at 0 - 20℃; for 2h; Inert atmosphere;	General procedure: Ketones 2a-f (0.083 mmol - 5.40 mmol) was combined with the corresponding hydrazine (3t-z; 1.09 eq)and methanol (0.05 M) in an oven dried round bottomed flask and stirred at 30 °C for 1 hour. Thetemperature was raised to 50 °C for an additional 2 hours. The reaction was cooled to 0 °C and sodiumborohydride (1.05 eq) was added. The reaction was allowed to warm to room temperature, stirred for 2hours, quenched with brine, and extracted with dichloromethane (3 x 20 mL). The resultant organic layerwas dried over Na2SO4, decanted, and concentrated under vacuum. The crude hydrazide (4) was thensolubilized in THF (0.011 M) at 0 °C and triethylamine (2.6 eq) and triphosgene (0.67 eq) weresequentially added. The reaction was stirred at room temperature for 24 hours, quenched with brine, andextracted with ethyl acetate (3 x 20 mL). The resultant organic layer was dried over Na2SO4, decantedand concentrated under vacuum. Product purification was achieved by silica gel flash chromatography(gradient elution starting with 25:75 ethyl acetate:hexane and ending with a 50:50 ethyl acetate:hexane) toyield azoxazolones 5.

Reference： [1]Meza-Aviña, Maria Elena; Lingerfelt, Mary A.; Console-Bram, Linda M.; Gamage, Thomas F.; Sharir, Haleli; Gettys, Kristen E.; Hurst, Dow P.; Kotsikorou, Evangelia; Shore, Derek M.; Caron, Marc G.; Rao, Narasinga; Barak, Larry S.; Abood, Mary E.; Reggio, Patricia H.; Croatt, Mitchell P. [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 7, p. 1827 - 1830]

48
[ 127108-66-1 ]
[ 22227-25-4 ]
C₁₂H₉F₃N₄OS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	In ethanol Reflux;	General procedures for target compounds 8a-8x: General procedure: To a solution of corresponding benzoyl hydrazine 7 (3 mmol) in anhydrous ethanol (20 mL), an intermediate 6 (0.39 g, 3 mmol) was added. The resulting mixture was then stirred at refluxed temperature, when TLC analyses indicated the disappearance of the starting material, then cooled to room temperature, followed by filtered to obtain the solid. The solid was recrystallized in ethanol to give corresponding target compounds 8.

Reference： [1]Zhang, Jing-Peng; Li, Xiang-Yang; Dong, Ya-Wen; Qin, Yao-Guo; Li, Xin-Lu; Song, Bao-An; Yang, Xin-Ling [Chinese Chemical Letters, 2017, vol. 28, # 6, p. 1238 - 1242]

49
[ 76783-59-0 ]
[ 22227-25-4 ]

Reference： [1]ChemMedChem,2017,vol. 12,p. 972 - 985
[2]RSC Advances,2018,vol. 8,p. 6306 - 6314
[3]Turkish Journal of Chemistry,2019,vol. 43,p. 1075 - 1085

50
[ 22227-25-4 ]
4-amino-2,4-dihydro-5-(3-(trifluoromethyl)phenyl)-3H-1,2,4-triazole-3-thione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium hydroxide / ethanol / 3 h / 85 °C 2: hydrazine hydrate / ethanol / 100 °C / Sealed tube
	Multi-step reaction with 2 steps 1: potassium hydroxide / ethanol / 3 h / 85 °C 2: hydrazine hydrate / ethanol / 100 °C / Sealed tube

Reference： [1]Sevaille, Laurent; Gavara, Laurent; Bebrone, Carine; De Luca, Filomena; Nauton, Lionel; Achard, Maud; Mercuri, Paola; Tanfoni, Silvia; Borgianni, Luisa; Guyon, Carole; Lonjon, Pauline; Turan-Zitouni, Gülhan; Dzieciolowski, Julia; Becker, Katja; Bénard, Lionel; Condon, Ciaran; Maillard, Ludovic; Martinez, Jean; Frère, Jean-Marie; Dideberg, Otto; Galleni, Moreno; Docquier, Jean-Denis; Hernandez, Jean-François [ChemMedChem, 2017, vol. 12, # 12, p. 972 - 985]
[2]Baud, Damien; Bebrone, Carine; Becker, Katja; Benvenuti, Manuela; Cerboni, Giulia; Chelini, Giulia; Cutolo, Giuliano; De Luca, Filomena; Docquier, Jean-Denis; Feller, Georges; Fischer, Marina; Galleni, Moreno; Gavara, Laurent; Gresh, Nohad; Kwapien, Karolina; Legru, Alice; Mangani, Stefano; Mercuri, Paola; Pozzi, Cecilia; Sannio, Filomena; Sevaille, Laurent; Tanfoni, Silvia; Verdirosa, Federica; Berthomieu, Dorothée; Bestgen, Benoît; Frère, Jean-Marie; Hernandez, Jean-François [European Journal of Medicinal Chemistry, 2020, vol. 208]

51
[ 80194-68-9 ]
[ 22227-25-4 ]
2-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)-5-(3-(trifluoromethyl)phenyl)-1,3,4-oxadiazole [ No CAS ]

Reference： [1]RSC Advances,2018,vol. 8,p. 6306 - 6314

52
[ 98-98-6 ]
[ 22227-25-4 ]
N'-(3-(trifluoromethyl)benzoyl)picolinohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99%	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In N,N-dimethyl-formamide at 20℃;

Reference： [1]Zhang, Lei; Shi, Lei; Soars, Shafer Myers; Kamps, Joshua; Yin, Hang [Journal of Medicinal Chemistry, 2018, vol. 61, # 14, p. 5881 - 5899]

53
[ 874-24-8 ]
[ 22227-25-4 ]
3-hydroxy-N'-(3-(trifluoromethyl)benzoyl)picolinohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In N,N-dimethyl-formamide at 20℃;

Reference： [1]Zhang, Lei; Shi, Lei; Soars, Shafer Myers; Kamps, Joshua; Yin, Hang [Journal of Medicinal Chemistry, 2018, vol. 61, # 14, p. 5881 - 5899]

54
[ 35272-15-2 ]
[ 22227-25-4 ]
2-methyl-N′-(3-(trifluoromethyl)benzoyl)thiazole-4-carbohydrazide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 5881 - 5899

55
[ 5424-01-1 ]
[ 22227-25-4 ]
3-amino-N'-(3-(trifluoromethyl)benzoyl)pyrazine-2-carbohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In N,N-dimethyl-formamide at 20℃;

Reference： [1]Zhang, Lei; Shi, Lei; Soars, Shafer Myers; Kamps, Joshua; Yin, Hang [Journal of Medicinal Chemistry, 2018, vol. 61, # 14, p. 5881 - 5899]

56
[ 1462-86-8 ]
[ 22227-25-4 ]
3-amino-N'-(3-(trifluoromethyl)benzoyl)picolinohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In N,N-dimethyl-formamide at 20℃;

Reference： [1]Zhang, Lei; Shi, Lei; Soars, Shafer Myers; Kamps, Joshua; Yin, Hang [Journal of Medicinal Chemistry, 2018, vol. 61, # 14, p. 5881 - 5899]

57
[ 98-97-5 ]
[ 22227-25-4 ]
N′-(3-(trifluoromethyl)benzoyl)pyrazine-2-carbohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In N,N-dimethyl-formamide at 20℃;

Reference： [1]Zhang, Lei; Shi, Lei; Soars, Shafer Myers; Kamps, Joshua; Yin, Hang [Journal of Medicinal Chemistry, 2018, vol. 61, # 14, p. 5881 - 5899]

58
[ 5345-47-1 ]
[ 22227-25-4 ]
2-amino-N′-(3-(trifluoromethyl)benzoyl)nicotinohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In N,N-dimethyl-formamide at 20℃;

Reference： [1]Zhang, Lei; Shi, Lei; Soars, Shafer Myers; Kamps, Joshua; Yin, Hang [Journal of Medicinal Chemistry, 2018, vol. 61, # 14, p. 5881 - 5899]

59
[ 22227-25-4 ]
[ 27398-39-6 ]
3-chloro-N′-(3-(trifluoromethyl)benzoyl)pyrazine-2-carbohydrazide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 5881 - 5899

60
[ 486424-37-7 ]
[ 22227-25-4 ]
3-amino-6-bromo-N′-(3-(trifluoromethyl)benzoyl)pyrazine-2-carbohydrazide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 5881 - 5899

61
[ 22227-25-4 ]
[ 2727-13-1 ]
3-amino-6-chloro-N′-(3-(trifluoromethyl)benzoyl)pyrazine-2-carbohydrazide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 5881 - 5899

62
[ 22227-25-4 ]
1-(3-methylbut-2-en-1-yl)indoline-2,3-dione [ No CAS ]
N'-(1-(3-methylbut-2-en-1-yl)-2-oxoindolin-3-ylidene)-3-(trifluoromethyl)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With acetic acid In ethanol at 20℃; for 2h;	General method of synthesis of N'-(1-(3-methylbut-2-en-1-yl)-2-oxoindolin-3-ylidene) hydrazine derivatives (S1-S20) General procedure: To intermediate B (0.5 mmol, 109.5 mg) in ethanol (5 mL), substituted benzoyl hydrazine or phenylhydrazine (0.5 mmol) was added. Then 200 μL glacial acetic acid was dripped in. After 2 h, the mixture was filtered and dried. The target compounds S1-S20 was then obtained through silica column (PE:EA = 4:1 v/v). In some cases, ultrasonic vibration can contribute to precipitation. No cis-trans isomerism was found during reaction and NMR data indicated all this series were trans configuration.

Reference： [1]Yang, Yu-Shun; Su, Mi-Mi; Zhang, Xu-Ping; Liu, Qi-Xing; He, Zhen-Xiang; Xu, Chen; Zhu, Hai-Liang [Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 19, p. 3182 - 3186]

63
[ 22227-25-4 ]
2-(((3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl)methyl)thio)-5-(3-(trifluorom-ethyl)phenyl)-1,3,4-oxadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydroxide 2: potassium carbonate / acetonitrile / Reflux

Reference： [1]Yu, Gang; Chen, Shunhong; He, Feng; Luo, Dexia; Zhang, Yu; Wu, Jian [Turkish Journal of Chemistry, 2019, vol. 43, # 4, p. 1075 - 1085]

64
[ 1147550-11-5 ]
[ 22227-25-4 ]
5-(3-(trifluoromethyl)phenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide In water at 80℃; for 6h;	General Procedure 3: Ammonium Thiocyanate-Involved Ring Closing Reaction General procedure: To a solution of hydrazides (3a~3t, 8a, or 8b, 1.0 equiv.) 10% NaOH aqueous solution(1.5 mL/1 mmol) was added ammonium thiocyanate (3.0 equiv.), then the mixture was heatedto 80 C and stirred for 6 h. The mixture was then cooled to room temperature and filtered. The filtratewas neutralized to pH 3-4 by concentrated hydrochloric acid, and the resulting white solid was collectedby filtration. The combined filter cake was dried to give the 2,4-dihydro-3H-1,2,4-triazole-3-thiones in72%-83% yields.

Reference： [1]Yuan, Chen; Yan, Jie; Song, Chen; Yang, Fan; Li, Chao; Wang, Cheng; Su, Huiling; Chen, Wei; Wang, Lijiao; Wang, Zhouyu; Qian, Shan; Yang, Lingling [Molecules, 2020, vol. 25, # 1]

65
[ 22227-25-4 ]
3-(3-(trifluoromethyl)phenyl)-6,7-dihydro-5H-[1,2,4]triazolo[3,4-b][1,3]thiazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium hydroxide / water / 6 h / 80 °C 2.1: sodium hydrogencarbonate; potassium hydroxide / isopropyl alcohol / 0.5 h / 20 °C 2.2: 6 h / 80 °C

Reference： [1]Yuan, Chen; Yan, Jie; Song, Chen; Yang, Fan; Li, Chao; Wang, Cheng; Su, Huiling; Chen, Wei; Wang, Lijiao; Wang, Zhouyu; Qian, Shan; Yang, Lingling [Molecules, 2020, vol. 25, # 1]

66
[ 39910-98-0 ]
[ 22227-25-4 ]
N’-(1-(4-morpholinophenyl)ethylidene)-3-(trifluoromethyl)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	In acetonitrile for 6h; Reflux;	2.1.1 Synthesis of substituted phenyl benzoyl/sulfonyl hydrazones 26-47 General procedure: 4′-Morpholineacetophenone (0.01mol), substituted phenyl benzoyl hydrazides (0.01mol) or substituted phenyl sulfonyl hydrazides (0.01mol) were dissolved in acetonitrile and the mixture was refluxed for 6h. After the reaction finished, it was left to cool down to precipitate. The precipitate was purified with ethanol [30-33].

Reference： [1]Öztürk, Mehmet; Demirtaş, Ibrahim; Iyidoğan, Ayşegül Karaküçük; Kurşun Aktar, Bedriye Seda; Oruç-Emre, Emine Elçin; Sıcak, Yusuf; Tok, Tuğba Taşkın; Yağlıoğlu, Ayse Şahin [Journal of Molecular Structure, 2020, vol. 1211]

67
[ 58710-61-5 ]
[ 22227-25-4 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrazine hydrate monohydrate
	With hydrazine monohydrate In methanol for 0.5h; Reflux;	Synthesis of substituted benzoic acid hydrazide (5a-m) General procedure: 0.05 mol of substituted benzaldehyde in 3 mL of methanol is mixed with 0.1 mol of 99% hydrazine hydrate, the rinsing isrefluxed for 30 min, the mixture is allowed to cool once the product formed, and the precipitated solid is filtered off. Theproduct obtained is purified by washing with plenty of water and crystallizing from ethanol [27, 28].
	With hydrazine monohydrate In methanol for 0.5h; Reflux;	Synthesis of substituted benzoic acid hydrazide (5a-m) General procedure: 0.05 mol of substituted benzaldehyde in 3 mL of methanol is mixed with 0.1 mol of 99% hydrazine hydrate, the rinsing isrefluxed for 30 min, the mixture is allowed to cool once the product formed, and the precipitated solid is filtered off. Theproduct obtained is purified by washing with plenty of water and crystallizing from ethanol [27, 28].

Reference： [1]Öztürk, Mehmet; Demirtaş, Ibrahim; Iyidoğan, Ayşegül Karaküçük; Kurşun Aktar, Bedriye Seda; Oruç-Emre, Emine Elçin; Sıcak, Yusuf; Tok, Tuğba Taşkın; Yağlıoğlu, Ayse Şahin [Journal of Molecular Structure, 2020, vol. 1211]
[2]Kurşun Aktar, Bedriye Seda; Sicak, Yusuf; Tatar, Gizem; Oruç-Emre, Emine Elçin [Turkish Journal of Chemistry, 2022, vol. 46, # 1, p. 236 - 252]
[3]Kurşun Aktar, Bedriye Seda; Sicak, Yusuf; Tatar, Gizem; Oruç-Emre, Emine Elçin [Turkish Journal of Chemistry, 2022, vol. 46, # 1, p. 236 - 252]

68
[ 22532-62-3 ]
[ 22227-25-4 ]
3-trifluoromethyl-N'-(4-bromo-2-hydroxybenzylidene)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With acetic acid In methanol at 20℃;

Reference： [1]Del Poeta, Maurizio; Haranahalli, Krupanandan; Lazzarini, Cristina; Mallamo, John; McCarthy, J. Brian; Ojima, Iwao; Pathiranage, Senuri; Sun, Yi; Zambito, Julia [Journal of Medicinal Chemistry, 2019]

69
[ 90-59-5 ]
[ 22227-25-4 ]
3-trifluoromethyl-N'-(3,5-dibromo-2-hydroxybenzylidene)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With acetic acid In methanol at 20℃;

Reference： [1]Del Poeta, Maurizio; Haranahalli, Krupanandan; Lazzarini, Cristina; Mallamo, John; McCarthy, J. Brian; Ojima, Iwao; Pathiranage, Senuri; Sun, Yi; Zambito, Julia [Journal of Medicinal Chemistry, 2019]

70
[ 1927-94-2 ]
[ 22227-25-4 ]
3-trifluoromethyl-N'-(3-chloro-2-hydroxybenzylidene)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With acetic acid In methanol at 20℃;

Reference： [1]Del Poeta, Maurizio; Haranahalli, Krupanandan; Lazzarini, Cristina; Mallamo, John; McCarthy, J. Brian; Ojima, Iwao; Pathiranage, Senuri; Sun, Yi; Zambito, Julia [Journal of Medicinal Chemistry, 2019]

71
[ 1829-34-1 ]
[ 22227-25-4 ]
3-trifluoromethyl-N'-(3-bromo-2-hydroxybenzylidene)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With acetic acid In methanol at 20℃;

Reference： [1]Del Poeta, Maurizio; Haranahalli, Krupanandan; Lazzarini, Cristina; Mallamo, John; McCarthy, J. Brian; Ojima, Iwao; Pathiranage, Senuri; Sun, Yi; Zambito, Julia [Journal of Medicinal Chemistry, 2019]

72
[ 22227-25-4 ]
2-[(1E)-({5-sulfanylidene-3-[3-(trifluoromethyl)phenyl]-1,5-dihydro-4H-1,2,4-triazol-4-yl}imino)methyl]-benzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: potassium hydroxide / ethanol / 3 h / 85 °C 2: hydrazine hydrate / ethanol / 100 °C / Sealed tube 3: acetic acid / 2 h / Reflux

Reference： [1]Baud, Damien; Bebrone, Carine; Becker, Katja; Benvenuti, Manuela; Cerboni, Giulia; Chelini, Giulia; Cutolo, Giuliano; De Luca, Filomena; Docquier, Jean-Denis; Feller, Georges; Fischer, Marina; Galleni, Moreno; Gavara, Laurent; Gresh, Nohad; Kwapien, Karolina; Legru, Alice; Mangani, Stefano; Mercuri, Paola; Pozzi, Cecilia; Sannio, Filomena; Sevaille, Laurent; Tanfoni, Silvia; Verdirosa, Federica; Berthomieu, Dorothée; Bestgen, Benoît; Frère, Jean-Marie; Hernandez, Jean-François [European Journal of Medicinal Chemistry, 2020, vol. 208]

73
[ 22227-25-4 ]
4-[(E)-[(2,4-dihydroxyphenyl)methylidene]amino]-5-[3-(trifluoromethyl)phenyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: potassium hydroxide / ethanol / 3 h / 85 °C 2: hydrazine hydrate / ethanol / 100 °C / Sealed tube 3: acetic acid / 2 h / Reflux

Reference： [1]Baud, Damien; Bebrone, Carine; Becker, Katja; Benvenuti, Manuela; Cerboni, Giulia; Chelini, Giulia; Cutolo, Giuliano; De Luca, Filomena; Docquier, Jean-Denis; Feller, Georges; Fischer, Marina; Galleni, Moreno; Gavara, Laurent; Gresh, Nohad; Kwapien, Karolina; Legru, Alice; Mangani, Stefano; Mercuri, Paola; Pozzi, Cecilia; Sannio, Filomena; Sevaille, Laurent; Tanfoni, Silvia; Verdirosa, Federica; Berthomieu, Dorothée; Bestgen, Benoît; Frère, Jean-Marie; Hernandez, Jean-François [European Journal of Medicinal Chemistry, 2020, vol. 208]

74
[ 22227-25-4 ]
4-[(E)-[4-(phenylmethyloxy)phenyl]methylidene}amino]-5-[3-(trifluoromethyl)phenyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: potassium hydroxide / ethanol / 3 h / 85 °C 2: hydrazine hydrate / ethanol / 100 °C / Sealed tube 3: acetic acid / 2 h / Reflux

Reference： [1]Baud, Damien; Bebrone, Carine; Becker, Katja; Benvenuti, Manuela; Cerboni, Giulia; Chelini, Giulia; Cutolo, Giuliano; De Luca, Filomena; Docquier, Jean-Denis; Feller, Georges; Fischer, Marina; Galleni, Moreno; Gavara, Laurent; Gresh, Nohad; Kwapien, Karolina; Legru, Alice; Mangani, Stefano; Mercuri, Paola; Pozzi, Cecilia; Sannio, Filomena; Sevaille, Laurent; Tanfoni, Silvia; Verdirosa, Federica; Berthomieu, Dorothée; Bestgen, Benoît; Frère, Jean-Marie; Hernandez, Jean-François [European Journal of Medicinal Chemistry, 2020, vol. 208]

75
[ 22227-25-4 ]
[ 4755-77-5 ]
[ 1432053-94-5 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-(trifluoromethyl)benzene-1-carbohydrazide; Ethyl oxalyl chloride With triethylamine In dichloromethane at 0 - 20℃; for 6h; Stage #2: With toluene-4-sulfonic acid In dichloromethane at 20℃; for 18h;	2.2. General procedure for the preparation of intermediate compound (c) General procedure: Adding (b) (10.4 mmol), DCM (100 mL) and triethylamine (1.53 mL, 20.8 mmol) to a 250 mL three-neck bottle, Ethyl oxalyl chloride monoethylate was added at 0 °C and the reaction system was reacted at room temperature over 6 h. Then, triethylamine (0.77 mL, 10.4 mmol) and P-toluenesulfonyl chloride (1.98 g, 10.4 mmol) were added at room temperature for more than 18 h. 200 mL DCM was added to separate the organic layer. After the reaction, 100 mL saturated NaCl solution was used to wash and purify by silica gel column chromatography to get the product (c).
	Stage #1: 3-(trifluoromethyl)benzene-1-carbohydrazide; Ethyl oxalyl chloride With triethylamine In dichloromethane at -10 - 25℃; for 9h; Stage #2: With triethylamine; p-toluenesulfonyl chloride In ethanol

Reference： [1]Li, Yi-Tao; Yao, Wen-Qiang; Zhou, Si; Xu, Jun-Xing; Lu, Hui; Lin, Jian; Hu, Xiao-Yun; Zhang, Shao-Kai [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 34]
[2]Bai, Hangyu; Jiang, Weiqi; Li, Qi; Li, Tian; Ma, Shichuang; Shi, Baojun; Wu, Wenjun [Journal of Agricultural and Food Chemistry, 2021, vol. 69, # 39, p. 11572 - 11581]

76
[ 22227-25-4 ]
(Z)-(1-methyl-1H-tetrazol-5-yl)(phenyl)methanone O-((5-(3-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2-yl)methyl) oxime [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: triethylamine / dichloromethane / 6 h / 0 - 20 °C 1.2: 18 h / 20 °C 2.1: calcium chloride; sodium tetrahydroborate / ethanol / 18.5 h / 0 - 20 °C 3.1: phosphorus tribromide / dichloromethane / 0 - 20 °C 4.1: potassium carbonate / N,N-dimethyl-formamide / 6 h / 20 °C

Reference： [1]Li, Yi-Tao; Yao, Wen-Qiang; Zhou, Si; Xu, Jun-Xing; Lu, Hui; Lin, Jian; Hu, Xiao-Yun; Zhang, Shao-Kai [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 34]

77
[ 22227-25-4 ]
C₁₀H₆BrF₃N₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: triethylamine / dichloromethane / 6 h / 0 - 20 °C 1.2: 18 h / 20 °C 2.1: calcium chloride; sodium tetrahydroborate / ethanol / 18.5 h / 0 - 20 °C 3.1: phosphorus tribromide / dichloromethane / 0 - 20 °C

Reference： [1]Li, Yi-Tao; Yao, Wen-Qiang; Zhou, Si; Xu, Jun-Xing; Lu, Hui; Lin, Jian; Hu, Xiao-Yun; Zhang, Shao-Kai [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 34]

78
[ 22227-25-4 ]
[ 54014-10-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: triethylamine / dichloromethane / 6 h / 0 - 20 °C 1.2: 18 h / 20 °C 2.1: calcium chloride; sodium tetrahydroborate / ethanol / 18.5 h / 0 - 20 °C

Reference： [1]Li, Yi-Tao; Yao, Wen-Qiang; Zhou, Si; Xu, Jun-Xing; Lu, Hui; Lin, Jian; Hu, Xiao-Yun; Zhang, Shao-Kai [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 34]

79
[ 98879-62-0 ]
[ 22227-25-4 ]
2-[3-(trifluoromethyl)phenyl][1,2,4]triazolo[1,5-c]quinazolin-5(6H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide at 120℃; for 18h;	2-[3-(trifluoromethyl)phenyl][1 ,2,4]triazolo[1 ,5-c]quinazolin-5(6H)-one Methyl (2-cyanophenyl)carbamate (1.50 g, 8.51 mmol) and 3-(trifluoromethyl)benzohydrazide (CAS 22227-25-4, 1.74 g, 8.51 mmol) were stirred in N,N-dimethylformamide (30 mL) at 120 °C for 18 hours. Water was added to the mixture, precipitated product was filtered off, washed with water and dried under reduced pressure at 60 °C to give 1.72 g (61 % yield, 94 % purity) of the title compound.LC-MS (method 3): Rt = 0.79 min., MS (ESIpos): m/z = 331 (M+H)+1H-NMR (400 MHz, DMSO-d6): d [ppm] = 7.39 (t, 1H), 7.43 (d, 1H), 7.66-7.72 (m, 1H), 7.81 (t, 1H), 7.89 (s, 1H), 8.23 (dd, 1H), 8.43 (s, 1H), 8.48 (d, 1 H).

Reference： [1]Current Patent Assignee: BAYER AG; Helmholtz Association - WO2021/28382, 2021, A1 Location in patent: Page/Page column 76

80
[ 4374-71-4 ]
[ 22227-25-4 ]
C₁₃H₁₄F₃N₃O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide at 55℃; Sealed tube;	General procedure: To a solution of the amine R2-NH2 (1mmol, 1 equiv.) in anhydrous DMF (4mL) (in the case of hydrochloride salt, 1.5 equiv. of Na2CO3 (159mg) was added) was added DPT (244mg, 1.05mmol, 1.05 equiv.). After stirring at 55°C in a sealed tube for 1h30, the hydrazide R1-CONHNH2 (1.1mmol, 1.1 equiv.) was added and the mixture was again heated at 55°C for 1h30. After cooling to room temperatur, the solution was diluted in EtOAc and the organic phase was extracted five times with water, dried over MgSO4 and concentrated in vacuum. If necessary, the product was purified by gel column chromatography (EtOAc/Hexane).

Reference： [1]Gavara, Laurent; Legru, Alice; Verdirosa, Federica; Sevaille, Laurent; Nauton, Lionel; Corsica, Giuseppina; Mercuri, Paola Sandra; Sannio, Filomena; Feller, Georges; Coulon, Rémi; De Luca, Filomena; Cerboni, Giulia; Tanfoni, Silvia; Chelini, Giulia; Galleni, Moreno; Docquier, Jean-Denis; Hernandez, Jean-François [Bioorganic Chemistry, 2021, vol. 113]

81
[ 22227-25-4 ]
[ 84358-13-4 ]
tert-butyl 4-{2-[3-(trifluoromethyl)benzoyl]hydrazinecarbonyl}piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 20℃;	tert-butyl 4-{2-[3-(trifluoromethyl)benzoyl]hydrazinecarbonyl}piperidine-1-carboxylate To a solution of 1.5 g 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (6.54 mmol) in 25 mL DMF was added 3.4 mL Di-isopropylethylamine (20 mmol), 3.73 g HATU (9.8 mmol, CAS 148893-10-1) and 1.47 g 3-(trifluoromethyl)benzohydrazide (7.2 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and water, the layer were separated and the aqueous layer was extracted with ethyl acetate (2x). The combined organic layers were evaporated and 2.9 g of the crude product (75% purity) were obtained. LC-MS Method 2): R, = 0.84 min; MS (ESIpos): m/z = 415 [M+H]+

Reference： [1]Current Patent Assignee: BAYER AG; Helmholtz Association - WO2021/105117, 2021, A1 Location in patent: Page/Page column 344-345

82
[ 22227-25-4 ]
2-((2-(6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)ethyl)thio)-5-(3-(trifluoromethyl)phenyl)-1,3,4-thiadiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium hydroxide / ethanol 2: potassium carbonate / acetone / 6 h / Reflux

Reference： [1]Wang, Xiu; Duan, Wen-Gui; Lin, Gui-Shan; Chen, Ming; Lei, Fu-Hou [Research on Chemical Intermediates, 2021, vol. 47, # 10, p. 4029 - 4049]

83
[ 75-15-0 ]
[ 22227-25-4 ]
C₉H₅F₃N₂S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: carbon disulfide; 3-(trifluoromethyl)benzene-1-carbohydrazide With potassium hydroxide In ethanol Stage #2: With hydrogenchloride

Reference： [1]Wang, Xiu; Duan, Wen-Gui; Lin, Gui-Shan; Chen, Ming; Lei, Fu-Hou [Research on Chemical Intermediates, 2021, vol. 47, # 10, p. 4029 - 4049]

84
6-chloro-8-methyl-2-(5-methyl-1-(pyridin-2-yl)-1H-pyrazol-4-yl)-4H-benzo[d][1,3]oxazin-4-one [ No CAS ]
[ 22227-25-4 ]
N-(4-chloro-2-methyl-6-(5-(3-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2-yl)phenyl)-5-methyl-1-(pyridin-2-yl)-1H-pyrazole-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	Stage #1: 6-chloro-8-methyl-2-(5-methyl-1-(pyridin-2-yl)-1H-pyrazol-4-yl)-4H-benzo[d][1,3]oxazin-4-one; 3-(trifluoromethyl)benzene-1-carbohydrazide With sodium hydroxide In N,N-dimethyl-formamide at 25℃; for 6 - 12h; Stage #2: With N-ethyl-N,N-diisopropylamine; p-toluenesulfonyl chloride In N,N-dimethyl-formamide at 25℃; for 12h;

Reference： [1]Khallaf, Abdalla; Wang, Ping; Zhuo, Shuping; Zhu, Hongjun; Liu, Hui [Journal of Heterocyclic Chemistry, 2021, vol. 58, # 11, p. 2189 - 2202]

85
C₁₈H₁₄Cl₂N₄O₂ [ No CAS ]
[ 22227-25-4 ]
N-(4-chloro-2-methyl-6-(5-(3-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2-yl)phenyl)-1-(6-chloropyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	Stage #1: C₁₈H₁₄Cl₂N₄O₂; 3-(trifluoromethyl)benzene-1-carbohydrazide With sodium hydroxide In N,N-dimethyl-formamide at 25℃; for 6 - 12h; Stage #2: With N-ethyl-N,N-diisopropylamine; p-toluenesulfonyl chloride In N,N-dimethyl-formamide at 25℃; for 12h;

Reference： [1]Khallaf, Abdalla; Wang, Ping; Zhuo, Shuping; Zhu, Hongjun; Liu, Hui [Journal of Heterocyclic Chemistry, 2021, vol. 58, # 11, p. 2189 - 2202]

86
C₁₈H₁₄BrClN₄O₂ [ No CAS ]
[ 22227-25-4 ]
1-(4-bromopyridin-2-yl)-N-(4-chloro-2-methyl-6-(5-(3-(trifluoromethyl)phenyl)-1,3,4-oxadiazol-2-yl)phenyl)-5-methyl-1H-pyrazole-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	Stage #1: C₁₈H₁₄BrClN₄O₂; 3-(trifluoromethyl)benzene-1-carbohydrazide With sodium hydroxide In N,N-dimethyl-formamide at 25℃; for 6 - 12h; Stage #2: With N-ethyl-N,N-diisopropylamine; p-toluenesulfonyl chloride In N,N-dimethyl-formamide at 25℃; for 12h;

Reference： [1]Khallaf, Abdalla; Wang, Ping; Zhuo, Shuping; Zhu, Hongjun; Liu, Hui [Journal of Heterocyclic Chemistry, 2021, vol. 58, # 11, p. 2189 - 2202]

87
[ 2251-50-5 ]
[ 22227-25-4 ]
C₁₅H₄F₈N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In chloroform at 20℃;

Reference： [1]Hu, Die; Huang, Bin; Shi, Changsheng; Sun, Ning; Tao, Youtian; Yuan, Wenbo; Zhu, Mengyuan [Journal of Materials Chemistry C, 2021, vol. 9, # 38, p. 13384 - 13391]

88
[ 22227-25-4 ]
C₃₁H₃₇F₃N₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 9 h / -10 - 25 °C 2: potassium hydroxide / ethanol; water / 1 h / 0 °C 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / N,N-dimethyl-formamide; dichloromethane / 6 h / 25 °C 4: tetrabutyl ammonium fluoride / tetrahydrofuran / 25 °C

Reference： [1]Bai, Hangyu; Jiang, Weiqi; Li, Qi; Li, Tian; Ma, Shichuang; Shi, Baojun; Wu, Wenjun [Journal of Agricultural and Food Chemistry, 2021, vol. 69, # 39, p. 11572 - 11581]

89
[ 22227-25-4 ]
C₁₀H₄F₃N₂O₃^(1-)*K⁽¹⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 9 h / -10 - 25 °C 2: potassium hydroxide / ethanol; water / 1 h / 0 °C

Reference： [1]Bai, Hangyu; Jiang, Weiqi; Li, Qi; Li, Tian; Ma, Shichuang; Shi, Baojun; Wu, Wenjun [Journal of Agricultural and Food Chemistry, 2021, vol. 69, # 39, p. 11572 - 11581]

90
[ 22227-25-4 ]
C₃₇H₅₁F₃N₂O₅Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: triethylamine / dichloromethane / 9 h / -10 - 25 °C 2: potassium hydroxide / ethanol; water / 1 h / 0 °C 3: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / N,N-dimethyl-formamide; dichloromethane / 6 h / 25 °C

Reference： [1]Bai, Hangyu; Jiang, Weiqi; Li, Qi; Li, Tian; Ma, Shichuang; Shi, Baojun; Wu, Wenjun [Journal of Agricultural and Food Chemistry, 2021, vol. 69, # 39, p. 11572 - 11581]

91
[ 22227-25-4 ]
(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl-2-((4-methyl-5-(3-(trifluoromethyl)phenyl)-4H-1,2,4-triazol-3-yl)thio)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: ethanol / 3 h / 80 °C 1.2: 4 h / 100 °C 2.1: sodium acetate / ethanol; water / 2 h / 45 °C 2.2: 6 h / 80 °C

Reference： [1]Duan, Wen-Gui; Huang, Mei; Li, Bao-Yu; Lin, Gui-Shan [Molecules, 2021, vol. 26, # 22]

92
[ 22227-25-4 ]
[ 556-61-6 ]
C₁₀H₈F₃N₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-(trifluoromethyl)benzene-1-carbohydrazide; methyl thioisocyanate In ethanol at 80℃; for 3h; Stage #2: With sodium hydroxide at 100℃; for 4h;

Reference： [1]Duan, Wen-Gui; Huang, Mei; Li, Bao-Yu; Lin, Gui-Shan [Molecules, 2021, vol. 26, # 22]

93
[ 22227-25-4 ]
tert-butyl (2R,4R)-2-methyl-4-(5-(3-(trifluoromethyl)phenyl)-1,3,4-oxadiazole-2-carboxamido)pyrrolidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: potassium carbonate / dichloromethane / 0 - 20 °C 2: triethylamine; p-toluenesulfonyl chloride / dichloromethane / 2 h / 0 - 20 °C 3: 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine / tetrahydrofuran / 1 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: MISSION THERAPEUTICS LIMITED - WO2021/239863, 2021, A1

94
[ 22227-25-4 ]
N-((3R,5R)-5-methylpyrrolidin-3-yl)-5-(3-(trifluoromethyl)phenyl)-1,3,4-oxadiazole-2-carboxamide trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: potassium carbonate / dichloromethane / 0 - 20 °C 2: triethylamine; p-toluenesulfonyl chloride / dichloromethane / 2 h / 0 - 20 °C 3: 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine / tetrahydrofuran / 1 h / 0 - 20 °C 4: dichloromethane / 0 - 20 °C

Reference： [1]Current Patent Assignee: MISSION THERAPEUTICS LIMITED - WO2021/239863, 2021, A1

95
[ 22227-25-4 ]
N-((3R,5R)-1-cyano-5-methylpyrrolidin-3-yl)-5-(3-(trifluoromethyl)phenyl)-1,3,4-oxadiazole-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: potassium carbonate / dichloromethane / 0 - 20 °C 2.1: triethylamine; p-toluenesulfonyl chloride / dichloromethane / 2 h / 0 - 20 °C 3.1: 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine / tetrahydrofuran / 1 h / 0 - 20 °C 4.1: dichloromethane / 0 - 20 °C 5.1: potassium carbonate / tetrahydrofuran / 0.17 h / 20 °C 5.2: 0.75 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: MISSION THERAPEUTICS LIMITED - WO2021/239863, 2021, A1

96
[ 22227-25-4 ]
tert-butyl (2S,4R)-2-(methoxymethyl)-4-(5-(3-(trifluoromethyl)phenyl)-1,3,4-oxadiazole-2-carboxamido)pyrrolidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: potassium carbonate / dichloromethane / 0 - 20 °C 2: triethylamine; p-toluenesulfonyl chloride / dichloromethane / 2 h / 0 - 20 °C 3: 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine / tetrahydrofuran / 1 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: MISSION THERAPEUTICS LIMITED - WO2021/239863, 2021, A1

97
[ 22227-25-4 ]
N-((3R,5S)-5-(methoxymethyl)pyrrolidin-3-yl)-5-(3-(trifluoromethyl)phenyl)-1,3,4-oxadiazole-2-carboxamide trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: potassium carbonate / dichloromethane / 0 - 20 °C 2: triethylamine; p-toluenesulfonyl chloride / dichloromethane / 2 h / 0 - 20 °C 3: 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine / tetrahydrofuran / 1 h / 0 - 20 °C 4: dichloromethane / 0 - 20 °C

Reference： [1]Current Patent Assignee: MISSION THERAPEUTICS LIMITED - WO2021/239863, 2021, A1

98
[ 22227-25-4 ]
N-((3R,5S)-1-cyano-5-(methoxymethyl)pyrrolidin-3-yl)-5-(3-(trifluoromethyl)phenyl)-1,3,4-oxadiazole-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: potassium carbonate / dichloromethane / 0 - 20 °C 2.1: triethylamine; p-toluenesulfonyl chloride / dichloromethane / 2 h / 0 - 20 °C 3.1: 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine / tetrahydrofuran / 1 h / 0 - 20 °C 4.1: dichloromethane / 0 - 20 °C 5.1: potassium carbonate / tetrahydrofuran / 0.17 h / 20 °C 5.2: 0.75 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: MISSION THERAPEUTICS LIMITED - WO2021/239863, 2021, A1

99
[ 102879-42-5 ]
[ 22227-25-4 ]
[ 96989-50-3 ]
C₁₈H₁₆F₃N₃O₃S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-(2-aminoethyl)benzoic acid hydrochloride salt; di-2-pyridyl thionocarbonate With sodium carbonate In N,N-dimethyl-formamide at 55℃; for 1.5h; Sealed tube; Stage #2: 3-(trifluoromethyl)benzene-1-carbohydrazide In N,N-dimethyl-formamide at 55℃; for 1.5h; Sealed tube;

Reference： [1]Verdirosa, Federica; Gavara, Laurent; Sevaille, Laurent; Tassone, Giusy; Corsica, Giuseppina; Legru, Alice; Feller, Georges; Chelini, Giulia; Mercuri, Paola Sandra; Tanfoni, Silvia; Sannio, Filomena; Benvenuti, Manuela; Cerboni, Giulia; De Luca, Filomena; Bouajila, Ezeddine; Vo Hoang, Yen; Licznar-Fajardo, Patricia; Galleni, Moreno; Pozzi, Cecilia; Mangani, Stefano; Docquier, Jean-Denis; Hernandez, Jean-François [ChemMedChem, 2022, vol. 17, # 7]

100
[ 22227-25-4 ]
[ 134-96-3 ]
N’-(4-hydroxy-3,5-dimethoxybenzylidene)-3-(trifluoromethyl)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	In acetonitrile for 6h; Reflux;	N’-(4-hydroxy-3,5-dimethoxybenzylidene)substituted benzohydrazide (7a-m) General procedure: Substituted benzoic acid hydrazide dissolved in acetonitrile is dropped to 1 mol of 3,5-dimethoxy-4-hydroxybenzaldehydedissolved in acetonitrile, and the reaction is refluxed for 6 h. The product formation terminated the reaction by controllingwith TLC. The solid formed is filtered, dried, and purified with ethanol [27, 28].
80%	In acetonitrile for 6h; Reflux;	N’-(4-hydroxy-3,5-dimethoxybenzylidene)substituted benzohydrazide (7a-m) General procedure: Substituted benzoic acid hydrazide dissolved in acetonitrile is dropped to 1 mol of 3,5-dimethoxy-4-hydroxybenzaldehydedissolved in acetonitrile, and the reaction is refluxed for 6 h. The product formation terminated the reaction by controllingwith TLC. The solid formed is filtered, dried, and purified with ethanol [27, 28].

Reference： [1]Kurşun Aktar, Bedriye Seda; Sicak, Yusuf; Tatar, Gizem; Oruç-Emre, Emine Elçin [Turkish Journal of Chemistry, 2022, vol. 46, # 1, p. 236 - 252]
[2]Kurşun Aktar, Bedriye Seda; Sicak, Yusuf; Tatar, Gizem; Oruç-Emre, Emine Elçin [Turkish Journal of Chemistry, 2022, vol. 46, # 1, p. 236 - 252]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	22227-25-4	MDL No. :	MFCD00221476
Formula :	C₈H₇F₃N₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	HGUSYNBASYGAMC-UHFFFAOYSA-N
M.W :	204.15	Pubchem ID :	2777417
Synonyms :

Num. heavy atoms :	14
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.12
Num. rotatable bonds :	3
Num. H-bond acceptors :	5.0
Num. H-bond donors :	2.0
Molar Refractivity :	42.34
TPSA :	55.12 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.65 cm/s

Log Po/w (iLOGP) :	1.39
Log Po/w (XLOGP3) :	1.26
Log Po/w (WLOGP) :	2.46
Log Po/w (MLOGP) :	2.2
Log Po/w (SILICOS-IT) :	1.25
Consensus Log Po/w :	1.71

[ CAS No. 22227-25-4 ] {[proInfo.proName]}

Quality Control of [ 22227-25-4 ]

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[ 22227-25-4 ] Synthesis Path-Downstream 1~100

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[ 22227-25-4 ]

Fluorinated Building Blocks

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

Log S (ESOL) :	-2.02
Solubility :	1.96 mg/ml ; 0.00958 mol/l
Class :	Soluble
Log S (Ali) :	-2.02
Solubility :	1.97 mg/ml ; 0.00963 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.93
Solubility :	0.239 mg/ml ; 0.00117 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.39

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P264-P270-P271-P280-P301+P312+P330-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P362-P403+P233-P405-P501	UN#:	N/A
Hazard Statements:	H302-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.
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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.
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P270	Do not eat, drink or smoke when using this product.
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P281	Use personal protective equipment as required.
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P285	In case of inadequate ventilation wear respiratory protection.
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Response
Code	Phrase
P301	IF SWALLOWED:
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P308	IF exposed or concerned:
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P313	Get medical advice/attention.
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P320
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P321
P322
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P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
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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
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P411
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P413
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P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 22227-25-4 ] {[proInfo.proName]}

Quality Control of [ 22227-25-4 ]

Related Doc. of [ 22227-25-4 ]

Product Details of [ 22227-25-4 ]

Calculated chemistry of [ 22227-25-4 ] Expand+

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 22227-25-4 ]

Application In Synthesis of [ 22227-25-4 ]

[ 22227-25-4 ] Synthesis Path-Downstream 1~100

Technical Information

Related Functional Groups of [ 22227-25-4 ]

Fluorinated Building Blocks

Aryls

Amides

Hydrazides

Amines

Hydrazines

Trifluoromethyls

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 22227-25-4 ]