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Structure of 1939-99-7
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 1939-99-7 |
Formula : | C7H7ClO2S |
M.W : | 190.65 |
SMILES Code : | O=S(CC1=CC=CC=C1)(Cl)=O |
MDL No. : | MFCD00007455 |
InChI Key : | OAHKWDDSKCRNFE-UHFFFAOYSA-N |
Pubchem ID : | 74740 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H314 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅱ |
* 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 |
---|---|---|
96% | With tert-butylhypochlorite; In water; acetonitrile; at 0 - 20℃; | General procedure: Alkyl halide (or sulfate) (5 mmol) and thiourea (0.381 g, 5 mmol) were heated at reflux in EtOH (5 mL) for 1 h. After removal of the solvent in vacuum and washing with Et2O (3 × 5 mL), the corresponding S-alkyl isothiourea salt was obtained as a white solid in almost quantitative yield. Without purification, the product was transferred into a three-necked round-bottom flask equipped with a thermometer and an addition funnel in an ice-bath, followed by addition of water (0.45mL) and MeCN (10 mL). To the resultant vigorously stirred mixture was added dropwise a solution of t-BuOCl (2.86 mL) in MeCN (5 mL), keeping the inner temperature at 0?20 °C. The mixture was then stirred for 30 min. Removal of the solvent under vacuum, addition of Et2O (15 mL), washing with H2O (2 × 10 mL), drying over Na2SO4, and concentration under vacuum gave the desired product in high purity. The product was further purified by recrystalization from petroleum ether?EtOAc. |
82% | With hydrogenchloride; sodium chlorite; In acetonitrile; at 10 - 20℃; for 0.5h;Green chemistry; | General procedure: Step 1. An alkyl halide or mesylate (5 mmol) and thiourea (0.381 g, 5 mmol) wererefluxed in 5 mL of ethanol for 1 h. After removal of the solvent in vacuum thecorresponding S-alkyl isothiourea salt was obtained as white solid or sticky oil.Step 2. A 50 mL three-necked flask equipped with a thermometer and asolid-addition funnel was immersed in an ice-bath. To the flask was sequentiallyadded NaClO2 solid (for isothiouronium chlorides or sulfonate, 1.61 g, 15 mmol; forisothiouronium bromides, 2.14 g, 20 mmol, 85percent purity), MeCN (10 mL), and thenconc. HCl (for isothiouronium chlorides or sulfonate, 3 mL; for isothiouroniumbromides, 4 mL) during 1 min at such a rate that the inner temperature was maintainedless than 10 °C. Then S-alkyl isothiourea salt was slowly added througth the solidaddition-funnel to keep the inner temperature less than 20 °C. After the addtion, theresulting mixture was stirred for another 30 min. Then 25 mL of water was added, and the resultant mixture was evaporated in vacuum at 15 °C to remove acetonitrile. Afteraddition of 100 mL of water, the solid products were obtained by filtration on aBuchner funnel and dried under an infrared lamp, while the liquid products wereobtained by extraction with 15 mL of ethyl acetate, drying with Na2SO4, andconcentration in vacuum.For 1,4-dibromobutane, the amounts of thiourea, NaClO2 solid, MeCN, and conc.HCl were doubled. |
0.886 g | With sodium hypochlorite; sulfuric acid; In diethyl ether; water; at 0 - 20℃; for 0.5h;Green chemistry; | General procedure: The appropriate alkyl halide (or mesylate) (5 mmol) and thiourea (0.381 g, 5 mmol) were refluxed in EtOH (5 mL) for 1 h. After removal of the solvent in vacuum and washing with Et2O (3 × 5 mL), the corresponding S-alkyl isothiourea salt was obtained as a white solid or sticky oil in an almost quantitative yield. Without purification, the product was transferred into a three-necked round-bottomed flask equipped with a thermometer and an addition funnel in an ice-bath. Then, 6 M H2SO4 (2 mL), followed by Et2O (30 mL) were added. To the resultant vigorously stirred mixture was added dropwise 5percent bleach (for alkyl chlorides and mesylates, 30 mL; foralkyl bromides, 37.5 mL) by keeping the inner temperature 0?20 °C (for the preparation of alkanedisulfonyl dichlorides, 0.762 g, 10 mmol thiourea, 4 mL of 6 M H2SO4, 50 mL of Et2O, and 75 mL of 5percent bleach were used). After the addition, the mixture was stirred for another 30 min. The mixture was partitioned in a separatory funnel, and the ethereal phase was washed with brine (25 mL), dried (Na2SO4), and evaporated in vacuum to afford the desired product. The oily products were extracted with CHCl3 (3 × 2.5 mL) and evaporated to remove the by-product, bromine. If necessary, the products can be dissolved in minimal PE?EtOAc (5:1) and filtered through a column of silica gel (h = 5 cm) with PE?EtOAc (5:1) as eluent to remove the impurities (Table 2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example II-13 N-t-butoxycarbonyl-DL-4-(benzylsulfonylamino)phenylalanine In the same manner as in Example II-(11-2) and Example II-(11-3) except for using N-t-butoxycarbonyl-DL-4-aminophenylalanine ethyl ester in place of N-t-butoxycarbonyl-L-4-aminophenylalanine ethyl ester and using benzylsulfonyl chloride in place of benzenesulfonyl chloride, the reactions were carried out to obtain the title compound (overall yeield 92%) as palye yellowish foay product. 1H-NMR (CDCl3) delta; 7.33-7.25 (m, 5H), 7.12-6.99 (m, 4H), 6.90 (s, 1H), 5.06-4.88 (m, 1H), 4.63-4.57 (m, 1H), 4.32 (s, 2H), 3.18-3.02 (m, 2H), 1.43 (s, 9H). CI-MS (m/z); 291 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; | Example 135 3-Phenylmethanesulfonylamino-4-methoxy-N-phenyl-benzamide Prepared according to the procedure described for Example 121 using benzylsulfonyl chloride (1.90 g, 10 mmol), 3-amino-4-methoxy-N-phenyl-benzamide (2.43 g, 10 mmol), and pyridine (25 mL) to afford the product (2.5 g); m.p. 216-216 C. after trituration in hexanes/ethyl acetate (1:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20.0℃; for 16.0h; | Step 1 : N-((5-Bromothiophen-2-yl)methyl)-l-phenylmethanesulfonamide To a suspension of <strong>[1001414-56-7](5-bromo-2-thienyl)methanamine hydrochloride</strong> (2 g, 8.75 mmol) in dichloromethane (30 mL) was added N,N-diisopropylethylamine (3.2 mL, 18.4 mmol) and the reaction was stirred until complete dissolution. Phenylmethanesulfonyl chloride (1.75 g, 9.18 mmol) was then added and the reaction was stirred at ambient temperature for 16 hours. The reaction was diluted with dichloromethane and washed with water and brine, dried with MgS04, concentrated and purified by silica gel column chromatography (0-100% EtOAc in heptane) to give N-[(5-bromo-2-thienyl)methyl]-l-phenyl-methanesulfonamide (2.55 g, 84% yield). LCMS (m/z) ES+ 364 [M+18]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 3h; | Step 1 : N-(4-Bromo-2-fluorobenzyl)-l-phenylmethanesulfonamide To a solution of <strong>[112734-22-2](4-bromo-2-fluoro-phenyl)methanamine</strong> (3 g, 14.7 mmol) in dichloromethane (50 mL) was added N,N-diisopropylethylamine (3.3 mL, 19.1), followed by phenylmethanesulfonyl chloride (3.3 g, 17.6 mmol) and the reaction was stirred at ambient temperature for 3 hours. The reaction was diluted with more dichloromethane and washed with water and brine, dried with MgS04, concentrated and purified by silica gel column chromatography (20-100percent EtOAc in heptane) to give N-[(4-bromo-2-fiuoro-phenyl)methyl]-l- phenyl-methanesulfonamide (4.22 g, 80percent yield). LCMS (m/z) ES+ 358 [M+l]+. |
80% | With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 3h; | Step 1 : N-(4-Bromo-2-fluorobenzyl)-l-phenylmethanesulfonamide To a solution of <strong>[112734-22-2](4-bromo-2-fluoro-phenyl)methanamine</strong> (3 g, 14.7 mmol) in dichloromethane (50 mL) was added N,N-diisopropylethylamine (3.3 mL, 19.1 mmol), followed by phenylmethanesulfonyl chloride (3.3 g, 17.6 mmol) and the reaction was stirred at ambient temperature for 3 hours. The reaction was diluted with dichloromethane and washed with water and brine, dried with MgS04, concentrated and purified by silica gel column chromatography (20-100percent EtOAc in heptane) to give N- [(4-bromo-2-fluoro-phenyl)methyl]-l-phenyl-methanesulfonamide (4.22 g, 80percent yield). LCMS (m/z) ES+ 358 [M+l]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In tetrahydrofuran; at 0 - 20℃; for 16h; | Prep -N-(4-Chlorobutan-2-yl)- 1 -phenylmethanesulfonamide Step 1 : (R)-3-(Phenylmethylsulfonamido)butyl phenylmethanesulfonate To a solution of (3R)-3-aminobutan-l-ol (1.0 g, 11.2 mmol) and triethylamine (3.3 mL, 23.6 mmol) in tetrahydrofuran (37 mL) at 0 °C was slowly added phenylmethanesulfonyl chloride (4.49 g, 23.6 mmol) and the reaction was stirred at room temperature for 16 hours. MTBE (100 mL) was then added and the Et3N- HC1 salt was removed by filtration. The filtrate was then concentrated to give crude (R)-3-(phenylmethylsulfonamido)butyl phenylmethanesulfonate which was used without purification. LCMS (ESI), m/z, 398 [M+H] +. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 20℃; for 12.0h;Inert atmosphere; | General procedure: To the solution of amine (2a-10a) (1mmol) in DCM (5mL), triethylamine (2mmol) was added followed by benzylsulfonyl chloride, 2-Phenylethanesulfonyl chloride, benzene sulfonyl chloride, benzoyl chloride or phenylacetyl chloride (1.5mmol), and the mixture was stirred overnight at room temperature. The reaction was filtered, concentrated and solved by EA (20mL), then washed with ethyl acetate (3×15mL). The organic was combined and was dried over Na2SO4. After filtration, the filtrate was removed in vacuo. The residue was purified by silica gel column chromatography to give 2b-12b, 16b-17b. |