Structure of 35196-11-3
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CAS No. : | 35196-11-3 |
Formula : | C6H8N2O2S |
M.W : | 172.20 |
SMILES Code : | NC1=NC=C(S(=O)(C)=O)C=C1 |
MDL No. : | MFCD09946387 |
InChI Key : | YDVCUSJBYYFJPM-UHFFFAOYSA-N |
Pubchem ID : | 17861008 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P264-P270-P301+P312-P330 |
* 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 |
---|---|---|
79% | With potassium phosphate; copper(l) iodide; C16H18N2O2; In dimethyl sulfoxide; at 20℃; for 24h;Schlenk technique; Inert atmosphere; | General procedure: Sodium alkylsulfinate or sodium arylsulfinate (6.5 mmol), copper iodide (of which the dosage was shown in the following table), ligand (of which the dosage was shown in the following table) and potassium phosphate (5.0 mmol) were added into a 10 mL Schlenk tube. The tube was evacuated and filled with argon for three times, and then aryl chloride (5 mmol) and 4 mL of DMSO were added. The reaction mixture was homogeneously stirred at corresponding temperature for 24 hours. After cooling, the contents of the of Schlenk tube were washed with ethyl acetate, and filtered through silica gel and diatomite plug. The filtrate was concentrated and purified by column chromatography to give the corresponding product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N,N,N,N,N,N-hexamethylphosphoric triamide; | B. 6-(Methylsulfonyl)imidazo[1,2-a]pyridine-2-carbamic acid, methyl ester A suspension of 2-amino-5-(methylsulfonyl)pyridine (58.7 mmol) and methyl(chloroacetyl)carbamate (70 mmol) in 88 ml of HMPT is treated in a manner similar to that described above with respect to Example 1D to yield the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 3-chloro-benzenecarboperoxoic acid; | A. 2-Amino-5-(methylsulfonyl)pyridine The reaction of 74.6 mmol of 2-amino-5-(methylthio)pyridine with 31.8 g (156 mmol) of m-chloroperbenzoic acid carried out in a manner similar to that described with respect to Example 2A yields, after recrystallization from EtOH, the title A compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In 1,4-dioxane; at 90℃; | 6-Chloro-4-(5-methanesulfonyl-pyridin-2-ylamino)-2-methyl-2H-pyridazin-3-one 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (1 g, 4.48 mmol, Eq: 1.00), <strong>[35196-11-3]5-(methylsulfonyl)pyridin-2-amine</strong> (771 mg, 4.48 mmol, Eq: 1), 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (388 mg, 671 μmol, Eq: 0.15) and cesium carbonate (5.1 g, 15.7 mmol, Eq: 3.5) were suspended in dioxane (80.0 ml). Finally tris (dibenzylideneacetone)dipalladium(0) (307 mg, 336 μmol, Eq: 0.075) was added. The reaction mixture was heated to 90 C. over night. Reaction mixture was filtered over celite; washed with dioxane; concentrated. Crude material was triturated with dichloromethane and precipitate was collected by filtration to afford an off-white solid (70 mg, 222 μmol) 1H NMR (300 MHz, DMSO-d6) δ ppm 3.25 (s, 3H) 3.69 (s, 3H) 7.73 (d, J=8.69 Hz, 1H) 8.16 (dd, J=1.00 Hz, 1H) 8.42 (s, 1H) 8.83 (d, J=2.27 Hz, 1H) | |
5.05 g | In a round-bottom flask under argon was placed 1.14 g 95% sodium hydride in oil dispersion and 90 mL of tetrahydrofuran (Aldrich, anhydrous, no inhibitor). The mixture was cooled in an ice bath and 3.10 g <strong>[35196-11-3]5-(methylsulfonyl)pyridin-2-amine</strong> was added one portion. The cooling bath was removed and the mixture stirred at room temperature. After 15 minutes the mixture was cooled in an ice bath and 4.103 g of 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one was added in one portion. The cooling bath was removed and the mixture stirred at room temperature. After 90 minutes, the mixture was cooled in an ice bath and quenched by the dropwise addition of 90 mL of 0.5 M hydrochloric acid (gas evolution at first few drops, color change from red brown to light tan, 15 minute addition). The cooling bath was removed, the mixture stirred for an additional 15 minutes and the solid collected by suction filtration, washing with water, then ether. The solid was air dried overnight to afford the desired product (5.05 g) as a light yellow solid. H NMR (300 MHz, DMSO-d6) δ ppm 3.25 (s, 3 H) 3.69 (s, 3 H) 7.73 (d, J=8.69 Hz, 1 H) 8.16(dd, J=1.00 Hz, 1 H) 8.42 (s, 1 H) 8.83 (d, J=2.27 Hz, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
19% | With tris-(dibenzylideneacetone)dipalladium(0); 4a,9a-dihydro-9,9-dimethyl-4,5-bis(diphenylphosphino)-xanthene; caesium carbonate; In 1,4-dioxane; at 100℃; for 1h;Inert atmosphere; | Step 1 Methyl 6-chloro-4-(5-(methylsulfonyl)pyridin-2-ylamino)pyridazine-3-carboxylate A flask was charged with methyl 4,6-dichloropyridazine-3-carboxylate (200 mg, 0.966 mmol), <strong>[35196-11-3]5-(methylsulfonyl)pyridin-2-amine</strong> (183 mg, 1.06 mmol), Pd2(dba)3 (88.5 mg, 0.097 mmol), xantphos (112 mg, 0.193 mmol) and cesium carbonate (944 mg, 2.9 mmol). 1,4-Dioxane (6.0 mL) was added and argon was bubbled through it while sonicating the flask for 5 min. The flask was sealed and heated at 100 C. for 1 h. After cooling the mixture was filtered through celite and the filter cake washed with CH2Cl2. The filtrates were concentrated in vacuo then purified by chromatography (spherical silica 20-45 μM, 23 g, Versaflash Supelco, 0 to 100% ethyl acetate in hexanes, 30 min) to give methyl 6-chloro-4-(5-(methylsulfonyl)pyridin-2-ylamino)pyridazine-3-carboxylate (62 mg, 19%) as a light yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 11.18 (s, 1H) 9.31 (s, 1H) 8.98 (d, J=2.27 Hz, 1H) 8.19 (dd, J=8.59, 2.53 Hz, 1H) 7.09 (dd, J=8.84, 0.76 Hz, 1H) 4.15 (s, 3H) 3.15 (s, 3H). LCMS (EI/CI) m/z: 342.9 [M+H]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With palladium on activated charcoal; hydrogen; In methanol; under 2585.81 Torr; | Example 117c 5-(Methylsulfonyl)pyridin-2-amine 117c A mixture of 117b (2 g, 10 mmol), MeOH (10 mL), Pd/C (120 mg) in methanol (8 mL) was stirred f at 25 C under H2 (50 Psi) overnight. The Pd/C was removed by filtration and the filtrate was concentrated under reduced pressure to give 117c (1.7 g, 98%). MS: [M+H]+ 173. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In 1,4-dioxane; at 100℃; for 5h; | Example 117d 5-Bromo-1-methyl-3-(5-(methylsulfonyl)pyridin-2-ylamino)pyridin-2(1H)-one 117d A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 1,4-dioxane (15 mL), 117c (1.7 g, 10 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (5.2 g, 20 mmol) and cesium carbonate (6.4 g, 20 mmol). Xantphos (300 mg, 0.8 mmol) and Pd2(dba)3 (500 mg, 0.8 mmol) were added, and the reaction mixture was heated at 100 C for 5 h (hours). After this time the reaction was cooled to room temperature. The mixture was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified on flash column eluting with DCM:MeOH (20:1) to afford 117d(1 g, 30%). MS: [M+H]+ 358. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: A mixture of bromoacetaldehyde diethyl acetal (383 μL, 2.50 mmol) and aq. 2M HCl solution (1.4 mL, 2.7 mmol) is stirred at room temperature for 2 h. The reaction is then heated to 80 C. for 1 h. The reaction is cooled to 5 C. and the pH of the mixture adjusted to pH 8 by the addition of solid sodium bicarbonate. To the reaction mixture is added 5-(morpholine-4-sulfonyl)-pyridin-2-ylamine (300 mg, 1.2 mmol) and the resulting solution is warmed to room temperature and stirred overnight. The mixture is concentrated under reduced pressure and diluted with EtOAc (10 mL). The mixture is sonicated and filtered. The filtrate is concentrated under reduced pressure and the resulting residue is purified by flash silica gel column chromatography to provide 165 mg of 6-(morpholine-4-sulfonyl)-imidazo[1,2-a]pyridine (I-17). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | To a stirred solution of triphosgene (30 mg, 0.101 mmol) in dichloromethane (1 mL) was added a mixture of <strong>[35196-11-3]5-(methylsulfonyl)pyridin-2-amine</strong> (55 mg, 0.319 mmol) and N,N- diisopropylethylamine (0.07 mL, 0.401 mmol) in dichloromethane (1 mL) dropwise over 5 minutes. The mixture was stirred an additional 30 minutes and then a mixture of 4-(azetidin- 3-yloxy)benzo[d]thiazole hydrochloride (75 mg, 0.309 mmol, Intermediate 28) and N,N- diisopropylethylamine (0.12 mL, 0.687 mmol) in dichloromethane (1 mL) was added in one portion. The mixture was stirred overnight and then evaporated under reduced pressure. The remaining material was dissolved in a minimal amount of dichloromethane and chromatographed on silica gel, eluting with a 5%-70% ethyl acetate:ethanol (3:1 v/v) in hexanes gradient to give the title compound (44 mg, 35%) as a white solid. 1H NMR (400 MHz, CD3SOCD3) δ 3.24 (s, 3 H), 4.08 (br d, J = 8 Hz, 2 H), 4.56 (dd, J = 9, 7 Hz, 2 H), 5.24-5.30 (m, 1 H), 6.86 (d, J = 8 Hz, 1 H), 7.41 (t, J = 8 Hz, 1 H), 7.74 (dd, J = 9, 2 Hz, 1 H), 8.1 1 (d, J = 9 Hz, 1 H), 8.18 (dd, J = 9, 2 Hz, 1 H), 8.69 (d, J = 3 Hz, 1 H), 9.30 (s, 1 H), 10.04 (br s, 1 H); LC-MS (LC-ES) M+H = 405. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In 1,4-dioxane; at 110℃; for 3h;Sealed tube; Inert atmosphere; | In a 8mL vial containing 2-chloro-4-(2-fluoro-4-nitrophenoxy)pyridine (60 mg, 0.223 mmol, Example 1, Intermediate B), 5-(methylsulfonyl)pyndin-2-amine (50.0 mg, 0.290 mmol), Xantphos (15.51 mg, 0.027 mmol), Pd2dba3 (20 45 mg, 0.022 mmol) and CS2CO3 (218 mg, 0.670 mmol) was added dioxane (2mL). The reaction mixture was flushed with N?, sealed and heated to 110 C for 3 h. After cooling to rt, the reaction mixture a diluted with CTTCI3, filtered and concentrated. Column chromatography (12 g S1O2, 0 to 100% EtOAc-CHbCk) afforded the desired material (83.2 mg 92% yield). LC/MS (M+H) 405.0; HPLC RT 0.53 mm; Column: Waters XBridge Cl 8, 2.1 mm x 50 mm, 1.7 mth particles; Mobile Phase A: 5:95 acetomtrile:water with 0.1 % trifluoroacetic acid; Mobile Phase B: 95:5 acetonitrile:water with 0.1 % trifluoroacetic acid; Temperature: 50 C; Gradient: 0 %B to 100 %B over 3 min, then a 0.75 min hold at 100 % B; Flow: 1 mL/min; Detection: MS and UV (220 nm). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With methanesulfonic acid(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II); caesium carbonate; XPhos; In 1,4-dioxane; at 100℃;Inert atmosphere; | 1-(6-chloro-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3- yl)phenyl)amino)pyridin-3-yl)propan-1-one (100 mg, 0.23 mmol) and 5- methylsulfonylpyridin-2-amine (56 mg, 0.33 mmol) was suspended in 1,4-dioxane (10 mL), added XPhos (52 mg, 0.11 mmol), XPhos Pd G3 (46 mg, 0.05 mmol) and cesium carbonate (265 mg, 0.81 mmol). The mixture was stirred at 100C under nitrogen overnight. The reaction mixture was concentrated and purified with silica gel chromatography eluting with dichloromethane:methanol (20:1). The crude product was repurified by Prep-HPLC to yield 1-(4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3- yl)phenyl)amino)-6-((5-(methylsulfonyl)pyridin-2-yl)amino)pyridin-3-yl)propan-1-one (102 mg, 74%) as a solid. 1H NMR (300 MHz, DMSO-d6) δ 11.09 (s, 1H), 10.56 (s, 1H), 8.91 (s, 1H), 8.65 - 8.54 (m, 2H), 8.12 (dd, J = 8.9, 2.6 Hz, 1H), 7.92 - 7.80 (m, 2H), 7.66 (dq, J = 8.0, 1.7 Hz, 2H), 7.34 (t, J = 7.9 Hz, 1H), 3.96 (s, 3H), 3.74 (s, 3H), 3.23 (s, 3H), 3.12 (q, J = 7.2 Hz, 2H), 1.14 (t, J = 7.2 Hz, 3H) LC-MS (ES, m/z): [M+H]+ 508.10 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With copper(l) iodide; N,N,N,N,-tetramethylethylenediamine; potassium carbonate; In dimethyl sulfoxide; at 100℃;Inert atmosphere; | 5-iodopyridin-2-amine (200 mg, 0.91 mmol), sodium methyl sulfinate (186 mg, 1.82 mmol) and potassium carbonate (125 mg, 0.91 mmol) was suspended in dimethyl sulfoxide (10 mL). Copper(I)iodide (35 mg, 0.18 mmol) and N,N,N′,N′- tetramethylethylenediamine (53 mg, 0.46 mmol) was added to the suspension and stirred at 100C under nitrogen overnight. The mixture was cooled, diluted with water and ethyl acetate. The biphasic mixture was passed through a celite bed. The organic layer was separated and washed with water, brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified with silica gel chromatography eluting with ethyl acetate to yield 5-(methylsulfonyl)pyridin-2-amine (130 mg, 83%) as a solid. |
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