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Structure of 175205-39-7
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CAS No. : | 175205-39-7 |
Formula : | C8H6FNS |
M.W : | 167.20 |
SMILES Code : | FC1=CC=C(C)C(N=C=S)=C1 |
MDL No. : | MFCD00046800 |
InChI Key : | QVCYTKXGZLOVFA-UHFFFAOYSA-N |
Pubchem ID : | 519443 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H301+H311+H331-H315-H319-H335-H227 |
Precautionary Statements: | P501-P261-P270-P210-P271-P264-P280-P370+P378-P337+P313-P305+P351+P338-P361+P364-P332+P313-P301+P310+P330-P302+P352+P312-P304+P340+P311-P403+P233-P403+P235-P405 |
Class: | 6.1 |
UN#: | 2810 |
Packing Group: | Ⅲ |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In diethyl ether; ethanol; chloroform; ethyl acetate; | EXAMPLE 28 1-Ethyl-3-(5-fluoro-2-methylphenyl)-2-thioxo-imidazolidin-4-one A mixture of the crude N-ethyl glycine (11.5 g), 5-fluoro-2-methylphenylisothiocyanate (10.42 g), triethylamine (12.5 g) and chloroform (300 mL) was heated at reflux for 6 hours. The solvent was evaporated. The residue was dissolved in ethyl acetate (500 mL) and washed with water (500 mL). The organic phase was evaporated to dryness. The residue was dissolved in ethanol (50 mL), then diluted with diethyl ether (200 mL). The solution was saturated with hydrogen chloride. The mixture was filtered. The solid was discarded. The filtrate was evaporated to dryness. The residue was dissolved in diethyl ether (300 mL) and washed with water (200 mL). The organic phase was dried over anhydrous sodium sulfate and evaporated to dryness. Crystallization from ethanol afforded the title compound (6.5 g) as a pink solid, m.p. 98-100 C. Anal. Calcd. for. C12 H13 F N2 O S: C, 57.13; H, 5.19; N, 11.10. Found: C, 56.88; H, 5.17; N, 11.05. Mass spectrum (EI, M.+) m/z 252. | |
With triethylamine; In diethyl ether; ethanol; chloroform; ethyl acetate; | EXAMPLE 7 1-Ethyl-3-(5-fluoro-2-methylphenyl)-2-thioxo-imidazolidin-4-one A mixture of the crude N-ethyl glycine (11.5 g), 5-fluoro-2-methylphenyl-isothiocyanate (10.42 g), triethyl amine (12.5 g) and chloroform (300 mL) was heated at reflux for 6 hours. The solvent was evaporated. The residue was dissolved in ethyl acetate (500 mL) and washed with water (500 mL). The organic phase was evaporated to dryness. The residue was dissolved in ethanol (50 mL), then diluted with diethyl ether (200 mL). The solution was saturated with hydrogen chloride. The mixture was filtered. The solid was discarded. The filtrate was evaporated to dryness. The residue was dissolved in diethyl ether (300 mL) and washed with water (200 mL). The organic phase was dried over anhydrous sodium sulfate and evaporated to dryness. Crystallization from ethanol afforded the title compound (6.5 g) as a pink solid, m.p. 98-100 C. Anal. Calcd. for. C12 H13 F N2 O S: C, 57.13; H, 5.19; N, 11.10. Found: C, 56.88; H, 5.17; N, 11.05. Mass spectrum (EI, M.+) m/z 252. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 4 1-Ethyl-3-(5-fluoro-2-methylphenyl)-2-thioxo-4,5-imidazolidinedione 5-Fluoro-2-methylphenyl isothiocyanate (16.7 g; 0.1 mol) was added dropwise to aqueous ethylamine (120 mL of 70% solution). The mixture was stirred for 2 hour at ambient temperature. Excess ethylamine was removed under a stream of nitrogen. The residue was diluted with water. The solids were collected by filtration, washed with water and dried. The solid was dissolved in ether and washed with water. The organic phase was dried over anhydrous magnesium sulfate then evaporated to dryness to give N-(5-fluoro-2-methylphenyl)-N'-ethylthiourea (18.5 g), m.p. 93-95 C. Mass spectrum; (El, M.+) m/z 212. 1H-NMR (DMSO-d6; 300 MHz): δ9.01 (br s, 1H), 7.66 (br s, 1H), 7.25-7.18 (m, 2H), 6.96 (m, 1H), 3.45 (m, 2H), 2.13 (s, 3H), and 1.09 ppm (t, 3H). Anal. for C10H13FN2S: Calcd: C, 56.58; H, 6.17; N, 13.20. Found: C, 56.53; H, 6.04; N, 13.17. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In chloroform; | EXAMPLE 10 2-Ethylsulfanyl-3-(5-fluoro-2-methylphenyl)-3,5-dihydro-imidazol-4-one A mixture of glycinamide hydrochloride (4.42 g), 5-fluoro-2-methylphenyl-isothiocyanate (6.68 g), triethyl amine (4.1 g), and chloroform (150 mL) was stirred at ambient temperature for 18 hours. The precipitate was collected by filtration, washed with chloroform and air dried to give 2-[3-(5-Fluoro-2-methylphenyl)-thioureido]-acetamide (7.6 g), m.p. 172-174 C. (dec.). This compound was used without further purification in the next paragraph. | |
With triethylamine; In chloroform; | EXAMPLE 10 2-Ethylsulfanyl-3-(5-fluoro-2-methylphenyl)-3,5-dihydroimidazol-4-one A mixture of glycinamide hydrochloride (4.42 g), 5-fluoro-2-methylphenylisothiocyanate (6.68 g), triethyl amine (4.1 g), and chloroform (150 mL) was stirred at ambient temperature for 18 hours. The precipitate was collected by filtration, washed with chloroform and air dried to give 2-[3-(5-Fluoro-2-methylphenyl)-thioureido]acetamide (7.6 g), m.p. 172-174 C. (dec.). This compound was used without further purification in the next paragraph. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | In methanol; chloroform; ethyl acetate; | (Step 1) Synthesis of methyl (2-(5-fluoro-2-methylphenylamino)-6-benzoxazolyl)acetate In methanol (50 ml), <strong>[175205-39-7]5-fluoro-2-methylphenyl isothiocyanate</strong> (2.00 g, 12.0 mmol) was added to methyl 4-amino-3-hydroxyphenylacetate (2.17 g, 12.0 mmol) at room temperature. After stirring for 27 hours, mercuric oxide (yellow) (3.12 g, 14.4 mmol) was added to the reaction mixture and the resulting mixture was heated at 70ØC for 4 hours. After cooling to room temperature, the reaction mixture was filtered through Celite. The filtrate was washed with methanol. The filtrate was distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from chloroform/ethyl acetate (10/1) eluate fractions, methyl (2-(5-fluoro-2-methylphenylamino)-6-benzoxazolyl)acetate (1.73 g, 46%) was obtained as a pale brown oil. 1H-NMR (CDCl3) δ: 2.13 (s, 3H), 3.705 (s, 2H), 3.711 (s, 3H), 6.74 (dt, J=8.3,2.7Hz, 1H), 6.81 (br, 1H), 7.15 (dd, J=8.1,1.7Hz, 2H), 7.31 (d, J=1.2Hz, 1H), 7.44 (d, J=8.1Hz, 1H), 8.09 (dd, J=11.0,2.7Hz, 1H). MS (ESI) m/z 315 (M++1). |
46% | In methanol; chloroform; ethyl acetate; | (Step 1) Synthesis of methyl (2-(5-fluoro-2-methylphenylamino)-6-benzoxazolyl)acetate In methanol (50 ml), <strong>[175205-39-7]5-fluoro-2-methylphenyl isothiocyanate</strong> (2.00 g, 12.0 mmol) was added to methyl 4-amino-3-hydroxyphenylacetate (2.17 g, 12.0 mmol) and the resulting mixture was stirred at room temperature for 27 hours. Mercuric oxide (yellow) (3.12 g, 14.4 mmol) was added to the reaction mixture, followed by stirring at 70ØC for 4 hours. After cooling to room temperature, the reaction mixture was filtered through Celite, followed by washing with methanol. The filtrate was distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from chloroform/ethyl acetate (10/1) eluate fractions, methyl (2-(5-fluoro-2-methylphenylamino)-6-benzoxazolyl)acetate (1.73 g, 46%) was obtained as a brown oil. 1H-NMR (CDCl3) δ: 2.13 (s, 3H), 3.705 (s, 2H), 3.711 (s, 3H), 6.74 (dt, J=8.3,2.7Hz, 1H), 6.81 (br, 1H), 7.15 (dd, J=8.1, 1.7Hz; 2H), 7.31 (d, J=1.2Hz, 1H), 7.44 (d, J=8.1Hz, 1H), 8.09 (dd, J=11.0,2.7Hz, 1H). MS (ESI) m/z 315 (M++1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | In methanol; chloroform; | (Step 7) Synthesis of ethyl (2-(5-fluoro-2-methylphenylamino) -4-fluoro-6-benzoxazolyl)acetate Under stirring at room temperature, ethyl 4-amino-3-fluoro-5-hydroxyphenylacetate (233 mg, 1.10 mmol) was added to a solution of <strong>[175205-39-7]5-fluoro-2-methylphenyl isothiocyanate</strong> (184 mg, 1.10 mmol) in methanol (20 ml). The resulting mixture was stirred at 70ØC for 1 hour. To the reaction mixture was added mercuric oxide (yellow) (262 mg, 1.21 mmol), followed by stirring for further 30 minutes. After cooling to room temperature, the reaction mixture was filtered through Celite. The filtrate was washed with methanol and then, distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from chloroform/methanol (10/1) eluate fractions, ethyl (2-(5-fluoro-2-methylphenylamino)-4-fluoro-6-benzoxazolyl)acetate (216 mg, 57%) was obtained as a pale yellow solid. 1H-NMR (CDCl3) δ: 1.28 (t, J=7.2Hz, 3H), 2.32 (s, 3H), 3.67 (s, 2H), 4.18 (q, J=6.8, 14.4Hz, 2H), 6.74-6.79 (m, 1H), 6.92-6.97 (m, 2H), 7.14-7.17 (m, 2H), 8.05-8.09 (m, 1H). MS (ESI) m/z 347 (M++1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With calcium carbonate; In hydrogenchloride; dichloromethane; water; | (Step 6) Synthesis of 5-fluoro-2-methylphenyl isothiocyanate Under stirring at 0ØC, a solution of 5-fluoro-2-methylaniline (1.23 g, 9.84 mmol) in methylene chloride (10 ml) was added dropwise to a mixture of calcium carbonate (2.46 g, 24.6 mmol) and thiophosgene (750 æl, 9.84 mmol) in a methylene chloride/water (1/1, 40 ml) mixture. After completion of the dropwise addition, the reaction mixture was stirred further at 0ØC for 35 minutes. The reaction mixture was poured in ice-1N HCl, followed by extraction with chloroform. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and distilled under reduced pressure to remove the solvent to give 5-fluoro-2-methylphenyl isothiocyanate (1.45 g, 88%) as a brown oil. MS (ESI) m/z 167 (M+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | In ethanol; at 80℃; | General procedure: Nicotinic/isonicotinic hydrazides (1mmol) were reacted with various substituted phenyl isothiocyanates (1mmol) in absolute ethanol and the reaction mixture was refluxed under at 80C for 30-50min. The reaction progress was monitored via TLC. After the completion of reaction, the precipitates formed were filtered, washed with hot hexane followed by ethanol, it was later dried and collected. The structures of compounds (3-27) were characterized by using various spectroscopic techniques such as EI-MS, 1H NMR, and 13C NMR |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | In ethanol; at 80℃; | General procedure: The reaction mixture containing 4-chlorophenyl hydrazide(0.5 mmol) and aryl isothiocyanate (0.5 mmol) in absolute ethanol(10 mL) was refluxed at 80 C for 20-30 min and monitored throughTLC. Precipitates were appeared in the reaction mixture which werefiltered and washed with hot hexane then cold ethanol [37]. Productwas dried in vacuum and collected. All compounds 1-25 were characterizedby spectroscopic techniques such as EI-MS and 1H NMR.Spectral data of all compounds are as follows. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.89% | In acetonitrile; at 80℃; | General procedure: First atenolol (1 mmol) was completely dissolved in acetonitrile(10 mL) into a dried 100 mL round-bottomed flask. Then, substitutedphenyl isothiocayante (1 mmol) was also added into it and refluxed at80 C. Product formation as well as purity of compounds were confirmedby thin layer chromatography [TLC system; 100% ethyl acetateEtOAc]. Precipitates were appeared within 5-15 min which were filtered,washed with hot water, and crystallized from ethanol. Structuresof all synthetic compounds were deduced by various spectroscopicanalysis. Spectroscopic data of all compounds is given in supplementaryinformation. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With sodium hydrogencarbonate; at 120℃; for 24h; | General procedure: A clean washed boiling tube equipped with a magnetic stir bar was charged with aniline 1a (0.0930g, 1 mmol), phenyl isothiocyanates 2a (0.1350 g, 1 mmol), 0.5 mmol of NaHCO3 and dichloroethane (1mL), the above mixture was stirred for 24 h at 120 C temperature. After completion of the reaction, the mixture was poured into 10 mL of NaHCO3 solution. The product was extracted with ethyl acetate (10 mL × 3) and dried with anhydrous Na2SO4. Removal of the solvent under reduced pressure, the left-out residue was purified through column chromatography using silica gel (20% EtOAc/hexane) to obtained (Z)-N,3-diphenylthiazolidin-2-imine 4a in 82 % yield (0.2082g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | In butan-1-ol;Reflux; | General procedure: 4-Aminobenzohydrazide (2) was added to 1.1 equimolar amount of corresponding phenyl isothiocyanate (3a-3f) or phenyl iso- cyanate (4a-4f) solutions in 10 mL n-butanol (3a-3f) or chloro- form (4a-4f). The mixture was stirred at reflux conditions and then cooled to room temperature after the reaction was completed. Following the evaporation of the solvent under atmospheric pres- sure, the resulting precipitate was filtered offand washed with n- butanol (3a-3f) or chloroform (4a-4f). The solid residue was puri- fied by crystallization from ethanol to afford the target compounds (3a-3f, 4a-4f). |