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Structure of 94789-37-4
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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. : | 94789-37-4 |
Formula : | C6H5N3O |
M.W : | 135.12 |
SMILES Code : | N#CC1=NC=CC(OC)=N1 |
MDL No. : | MFCD13705422 |
InChI Key : | POLUXOCVEJOPOJ-UHFFFAOYSA-N |
Pubchem ID : | 13221189 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H301-H311-H331 |
Precautionary Statements: | P261-P264-P270-P271-P280-P302+P352-P304+P340-P310-P330-P361-P403+P233-P405-P501 |
Class: | 6.1 |
UN#: | 2811 |
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 |
---|---|---|
50% | 2-chloro-4-methoxypyrimidine (500 mg, 3.45 mmol) was combined with zinc cyanide (242 mg, 2.07 mmol) and tetrakis (triphenylphosphne)palladium (0) (159 mg, 0.14 mmol) in DMF (10 mL) and the slurry was heated at 800C under nitrogen for 6h. The mixture was cooled to rt, diluted with EtOAc (50 mL) and washed twice with 2N ammonium hydroxide (50 mL). The EtOAc solution was washed with brine (20 mL) and concentrated in vacuo to provide the crude mixture. The crude was then purified by column chromatography (10% EtOAc in hexanes) to afford 4-methoxypyrimidine-2-carbonitrile in 50% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonia; hydrogen;nickel; In methanol; water; under 2844.39 Torr; for 2.0h; | To <strong>[94789-37-4]4-methoxypyrimidine-2-carbonitrile</strong> (370 mg) in MeOH (5 mL), aqueous ammonium hydroxide (1 mL) and Raney Nickel (catalytic) were added and the reaction mixture was hydrogenated at 55 psi for 2 h. Then the reaction mixture was filtered and solvent evaporated to afford (4-methoxypyrimidin-2-yl)methanamine, which was carried to next step without purification. | |
979 mg | With hydrogen; nickel; acetic acid; at 20℃; under 2585.81 Torr; for 1.66667h; | Step 2: 1-(4-methoxypyrimidin-2-yl)methanamine: [00321] 4-Methoxypyrimidine-2-carbonitrile (908 mg, 6.72 mmol) and acetic acid (25 mL) were added to nickel (2.7 g, 46.0 mmol) in a 50 mL pressure bottle and shaken under a 50 psi hydrogen atmosphere at room temperature for 100 minutes. The reaction mixture was then filtered, partially concentrated and chromatographed on silica (0 to 15% concentrated aqueous ammonium hydroxide/acetonitrile). Mixed fractions were rechromatographed as before and material from both chromatographies was combined to give the titled compound (979 mg). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.79 (s, 2H), 3.93 (s, 3H), 6.78 (d, J = 5.8 Hz, 1H), 8.46 (d, J = 5.8 Hz, 1H); MS (DCI) m/z 140 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With 3-quinuclidinol; In dimethyl sulfoxide; at 60℃; for 2.5h; | General procedure: A mixture of 2-chloropyrimidines(10 mmol), potassium cyanide (13-15 mmol), water (20 mmol), and DMSO(20 mL) was heated to 60 C. A solution of 3-quinuclidinol (0.1-0.2 mmol) inDMSO(5 mL) was added to the reaction mixture over 0.5 h. The reaction mixturewas stirred at 50-70 C for additional hours as specified in Table 1. Uponcompletion, the mixture was cooled to room temperature and water (50 mL) wasadded. The resulting mixture was extracted with isopropyl acetate (3 40 mL)(product 7a precipitated out after water addition and was collected by filtration).The combined organic layers were washed with water (2 30 mL), dried overMgSO4, filtered, and concentrated under vacuum to give crude 2-cyanopyrimidines, which were purified by column chromatography (SiO2) to afford pureproducts. |
4.361 g | With 3-quinuclidinol; In water; acetonitrile; at 50℃; for 2.0h; | To a solution of potassium cyanide (2.70 g, 41.5 mmol) in water (5 mL) was added 2- chloro-4-methoxypyrimidine (4.99 g, 34.5 mmol), 3-quinuclidinol (1.10 g, 8.65 mmol) and acetonitrile (70 mL). The mixture was heated at 50 C for two hours, brought to room temperature and filtered with an acetonitrile rinse. The filtrate was concentrated, and the residue extracted first with tert-butyl methyl ether and then with 1:1 ethyl acetate/tert-butyl methyl ether. Extracts were sequentially filtered through a short plug of silica (10 g) to give the titled compound (4.361 g). 1H NMR (400 MHz, CDCl3) δ ppm 4.05 (s, 3H), 6.92 (d, J = 5.8 Hz, 1H), 8.49 (d, J = 5.8 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ ppm 54.9, 111.8, 115.6, 144.2, 157.7, 169.8; MS (DCI) m/z 153 (M+NH4)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen; In ethanol; at 20℃; under 2327.23 Torr; for 2.0h; | To a solution of Raney-Ni (25 mg, 0.296 mmol) in EtOH (5 mL) was added 4- methoxypyrimidine-2-carbonitrile (200 mg, 1 .48 mmol) and Boc20 (355 mg, 1 .63 mmol, 0.374 mL) under N2, then the reaction mixture was stirred at room temperature under H2(45 psi) for 2 hours. The reaction mixture was filtered through celite and concentrated under reduced pressure to give a residue. The residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to give terf-butyl N-[(4-methoxypyrimidin-2- yl)methyl]carbamate. | |
With hydrogen; In ethanol; at 20℃; under 2327.23 Torr; for 2.0h; | To a solution of Raney-Ni (25 mg, 0.296 mmol) in EtOH (5 mL) was added 4-methoxypyrimidine-2- carbonitrile (200 mg, 1.48 mmol) and Boc2O (355 mg, 1.63 mmol, 0.374 mL) under N2, then the reaction mixture was stirred at room temperature under H2 (45 psi) for 2 hours. The reactionmixture was filtered through celite and concentrated under reduced pressure to give a residue. The residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to give tert-butyl N-[(4-methoxypyrimidin-2-yl)methyl]carbamate. | |
With hydrogen; In ethanol; at 20℃; under 2327.23 Torr; for 2.0h; | To a solution of 349 Raney-Ni (25 mg, 0.296 mmol) in 25 EtOH (5 mL) was added 438 <strong>[94789-37-4]4-methoxypyrimidine-2-carbonitrile</strong> (200 mg, 1.48 mmol) and Boc2O (355 mg, 1.63 mmol, 0.374 mL) under N2, then the reaction mixture was stirred at room temperature under H2 (45 psi) for 2 hours. The reaction mixture was filtered through celite and concentrated under reduced pressure to give a residue. The residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to give 440 tert-butyl N-[(4-methoxypyrimidin-2-yl)methyl]carbamate. |
With hydrogen; In ethanol; at 20℃; under 2327.23 Torr; for 2.0h; | To a solution of Raney-Ni (25 mg, 0.296 mmol) in EtOH (5 mL) was added 4-methoxypyrimidine-2- carbonitrile (200 mg, 1.48 mmol) and B0C2O (355 mg, 1.63 mmol, 0.374 mL) under N2, then the reaction mixture was stirred at room temperature under H2 (45 psi) for 2 hours. The reaction mixture was filtered through celite and concentrated under reduced pressure to give a residue. The residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to give ferf-butyl //-[(4-methoxypyrimidin-2-yl)methyl]carbamate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1-methyl-pyrrolidin-2-one; at 140℃; for 1.0h;Sealed tube; Microwave irradiation; | 2-chloro-4-methoxy-pyrimidine (600 mg, 4.15 mmol) and Zn(CN)2(292 mg, 2.49 mmol) and Pd(dppf)CI2(607 mg, 0.83 mmol) were taken up into a microwave tube in NMP (3 mL). The sealed tube was heated at 140C for 1 hour under microwave irradiation. The reaction mixture was cooled to room temperature, filtered through celite and washed with ethyl acetate (20 mL). The reaction mixture was extracted with ethyl acetate (20 mL x 3) and the organic layers were washed with water (20 x 3mL), brine (20 mL), dried over anhydrous Na2S04, filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to give 4- methoxypyrimidine-2-carbonitrile. | |
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1-methyl-pyrrolidin-2-one; at 140℃; for 1.0h;Sealed tube; Microwave irradiation; | 2-chloro-4-methoxy-pyrimidine (600 mg, 4.15 mmol) and Zn(CN)2 (292 mg, 2.49 mmol) andPd(dppf)C12 (607 mg, 0.83 mmol) were taken up into a microwave tube in NMP (3 mL). The sealed tube was heated at 140C for 1 hour under microwave irradiation. The reaction mixture was cooled to room temperature, filtered through celite and washed with ethyl acetate (20 mL). The reaction mixture was extracted with ethyl acetate (20 mL x 3) and the organic layers were washed with water (20 x 3mL), brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated under reducedpressure to give a residue. The residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to give 4-methoxypyrimidine-2-carbonitrile. | |
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1-methyl-pyrrolidin-2-one; at 140℃; for 1.0h;Sealed tube; Microwave irradiation; | 2-chloro-4-methoxy-pyrimidine (600 mg, 4.15 mmol) and 423 Zn(CN)2 (292 mg, 2.49 mmol) and Pd(dppf)Cl2 (607 mg, 0.83 mmol) were taken up into a microwave tube in NMP (3 mL). The sealed tube was heated at 140 C. for 1 hour under microwave irradiation. The reaction mixture was cooled to room temperature, filtered through celite and washed with ethyl acetate (20 mL). The reaction mixture was extracted with ethyl acetate (20 mL×3) and the organic layers were washed with water (20×3 mL), brine (20 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to give 438 4-methoxypyrimidine-2-carbonitrile. |
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1-methyl-pyrrolidin-2-one; at 140℃; for 1.0h;Sealed tube; Microwave irradiation; | 2-chloro-4-methoxy-pyrimidine (600 mg, 4.15 mmol) and Zn(CN)2 (292 mg, 2.49 mmol) and (1068) Pd(dppf)Cl2 (607 mg, 0.83 mmol) were taken up into a microwave tube in NMP (3 mL). The sealed tube was heated at 140C for 1 hour under microwave irradiation. The reaction mixture was cooled to room temperature, filtered through celite and washed with ethyl acetate (20 mL). The reaction mixture was extracted with ethyl acetate (20 mL x 3) and the organic layers were washed with water (20 x 3mL), brine (20 mL), dried over anhydrous Na2S04, filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate) to give 4-methoxypyrimidine-2-carbonitrile. |
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