Structure of 102645-35-2
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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. : | 102645-35-2 |
Formula : | C6H2Cl2N2 |
M.W : | 173.00 |
SMILES Code : | ClC1=NC=C(Cl)C(=C1)C#N |
MDL No. : | MFCD13185482 |
InChI Key : | OZACVJUZLULNPG-UHFFFAOYSA-N |
Pubchem ID : | 13560210 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H317-H319 |
Precautionary Statements: | P280-P305+P351+P338 |
* 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 |
---|---|---|
40% | With hydrogen;platinum(IV) oxide; In AcOH; under 1551.49 Torr; for 6.0h; | Example 56 4-[(4-{1(trans-4-aminocyclohexyl)methyl]amino}-5-nitropyrimidin-2-yl)amino]methyl}-5-chloropyridin-2(1H)-one A mixture of <strong>[102645-35-2]3,6-dichloro-4-cyanopyridine</strong> (prepared according to WO 9633975) (3.40 g, 19.65 mmol) and PtO2 (0.40 g) in 1:1 Ac2O/AcOH (60 mL) was shaken in a Parr hydrogenation apparatus at 30 psi H2 for 6 h. The reaction mixture was filtered through a pad a celite and the filtered solids washed with EtOAc. The combined filtrate and washings were concentrated in vacuo and the resulting white solid purified by column chromatography on a 120 g ISCO combi-flash cartridge (silica gel, 20:80 to 100:0 EtOAc/hexane) to afford N-(2,5-Dichloro-pyridin-4-ylmethyl)-acetamide (1.73 g, 40%) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Then, 20 ml of phosphorus oxychloride was added to this 3-chloro-4-cyanopyridine N-oxide, and the mixture was refluxed under heating for 5 hours. After cooling, the reaction solution was gradually poured into an aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic layer was washed with water and then dried over anhydrous magnesium sulfate. Then, ethyl acetate was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate) to obtain 3.2 g of 4-cyano-2,5-dichloropyridine (melting point: 55 to 58 C.) and 2.5 g of 4-cyano-2,3-dichloropyridine (melting point: 65 to 69 C.). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ethanethiol; In hexane; ethyl acetate; isopropyl alcohol; | EXAMPLE 6 Preparation of 2-chloro-5-ethylthio-4-pyridinecarbonitrile and 5-chloro-2-ethylthio-4-pyridinecarbonitrile A solution of 2.77 g of ethanethiol in 30 ml of 2-propanol was added to a mixture containing 7.7 g of <strong>[102645-35-2]2,5-dichloro-4-pyridinecarbonitrile</strong> and 3.08 g of K2 CO3 in 60 ml of 2-propanol at 0 C. The reaction mixture was allowed to warm to room temperature and then stirred for 4 days, after which it was poured onto 200 g of ice, stirred and extracted with CH2 Cl2. Thin layer chromatography (using 10 percent ethyl acetate in hexane) disclosed the presence of three components. The CH2 Cl2 solution was dried and concentrated to 25 ml and then diluted with 12.5 ml of hexane to give a crystalline material which was separated by filtration and identified as 2-chloro-5-ethylthio-4-pyridinecarbonitrile. The filtrate was concentrated and separated on a Water's Prep LC 500 instrument eluted with 2 percent ethyl acetate in hexane. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
19.0 g (77%) | With trichlorophosphate; In acetonitrile; | EXAMPLE 5 2,5-Dichloro-4-pyridinecarbonitrile To 100 ml of acetonitrile was added 24.5 g of POCl3, followed by 27.1 g of 2,5-dichloro-4-pyridinecarboxaldehyde oxime (prepared as described in Example 4). The reaction mixture was heated at reflux temperature for 1 hour, then cooled and poured onto 300 g of ice. The pH of the mixture was adjusted to about pH 6 with K2 CO3 and filtered. The filtrate was extracted with 100 ml of CH2 Cl2. The filter cake and the CH2 Cl2 solution were combined, diluted with equal volumes of hexane, treated with charcoal, dried, and concentrated. The residue was purified by distillation on a Kugelrohr distillation apparatus (boiling point 80 C. at 0.2 mm pressure) to give 19.0 g (77%) of the desired 2,5-dichloro-4-pyridinecarbonitrile as a white solid, m.p. 58-60 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Al2O3; Cs2CO3; Pd2dba3; mixture of; In tetrahydrofuran; at 150.0℃; for 0.5h;Microwave; | In a microwave vial were added *catalyst powder (200mg), 2,5-dichloro-4-pyτidine carbonitrile (34.6mg), (15r,4Λ)-7,7-dimβthyl-l-([(35)-3-methyl-l piperazinyl]sulfonyl}methyl)bicyclo[2.2.1]heptan-2-one (125mg) and tetrahyrofuran (50μl). The resultant paste was heated in a microwave at 1500C for 30min, after which 50:50 DMSO: methanol was added to the reaction mixture. The solid was filtered and the filterate was purified by MDAP to give 5mg of desired product, 5-chloro-2-[(2S)-4-([(lS,4R)-7,7-dimetlryl-2- oxobicyclo[2.2.1]heρt-l-yl]methyl}sulfonyl)-2-methyl-l-piperazinyl]-4 pyridinecarbonitrile, as an off white solid. MS (ESI): 451 [M+H]+.*Catalyst powder composition: Cs2CO3 - Al2O3 (50%), + (l)+(2)+(3) + Pd2dba3 (3g,25mg, 15mg, 15mg, 20mg); Dry ingredients are stirred vigorously under nitrogen for ~ 1 hour to produce a free-flowing grey/purple powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate; In 1,2-dimethoxyethane; ethanol; hexane; water; ethyl acetate; | 5-Chloro-2-phenyl-isonicotinonitrile Tetralds(triphenylphosphine)palladium(0) (167 mg, 0.14 mmol) was added to a stirred solution of phenylboronic acid (423 mg, 3.47 mmol), <strong>[102645-35-2]2,5-dichloro-isonicotinonitrile</strong> (550 mg, 2.89 mmol) and sodium carbonate (3.5 mL of 2M aqueous solution) in dimethoxyethane (7 mL) and ethanol (3.5 mL). The resulting suspension was stirred at reflux for 3 hours, concentrated in vacuo and water (25 mL) added. The aqueous solution was extracted with ethyl acetate (*3) and the combined organic extracts were washed with brine, dried and concentrated. Purification by column chromatography using 2% v/v ethyl acetate in hexane as eluent afforded the title compound as a solid. MS (APCI+ve): [M+H]+ at m/z 215 (C12H7C1N2) requires [M+H]+ at m/z 215. 1H NMR δ (CDCl3) 8.8 (1H, s), 8.1-7.9 (3H, m), 7.6-7.4 (3H, m). |
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