Structure of 832735-58-7
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CAS No. : | 832735-58-7 |
Formula : | C7H8BrNO |
M.W : | 202.05 |
SMILES Code : | O=C1C=C(Br)C=CN1CC |
MDL No. : | MFCD23106157 |
InChI Key : | QOPDNHSCIIQOBK-UHFFFAOYSA-N |
Pubchem ID : | 23115965 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-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 |
---|---|---|
84% | General procedure: Under a nitrogen atmosphere, sodium hydride 60% in oil (0.23 g, 5.75 mmol) was added portionwise to a solution of 5-bromo-2(1 H)-pyridone (1 .00 g, 5.75 mmol) in dry tetrahydrofuran (20 mL). After 10 minutes stirring, iodopropane (1.68 mL, 17.24 mmol) was added and the reaction mixture was stirred at 50C for 40 hours. Water (10 mL) was added and the mixture was extracted with ethyl acetate (2 x 15 mL). The organic layer was washed with brine (2 x 10 mL), dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (dichloromethane/ethyl acetate 100/0 to 80/20) to provide 5-bromo-1-propyl-1 ,2- dihydropyridin-2-one (25a) (776 mg, 3.59 mmol, 62%). 1H NMR (400 MHz, CDCI3) delta 0.96 (t, J = 7.4 Hz, 3H), 1.77 (sext, J = 7.4 Hz, 2H), 3.85 (t, J = 7.4 Hz, 2H), 6.48 (d, J = 9.6 Hz, 1 H), 7.32 (dd, J = 2.7 Hz, J = 9.6 Hz, 1 H), 7.37 (d, J = 2.7 Hz, 1 H). MS m/z ([M+H]+) 216/218. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetone; at 60℃; for 3h; | Step D: 4-Bromo-l-ethylpyridin-2(lH)- A mixture of 4-bromopyridin-2-ol (100 mg, 0.57 mmol), bromoethane (124 mg, 1.1 mmol) and potassium carbonate (238 mg, 1.7 mmol) in acetone (5 mL) was stirred at 60 C for 3.0 h. The solution was allowed to cool to room temperature, filtered and the filter cake was washed with acetone (5 mL x 2). The filtrate was collected and concentrated under reduced pressure to give the crude product, which was purified by silica gel column chromatography (PE:EA = 20: 1) to afford the title compound as a white solid LC/MS m/z = 402.1 [M+H]+; 1H NMR (400 MHz, CDC13) delta 7.14 (d, 1 H), 6.81 (d, 1 H), 6.33 (dd, 1 H), 3.95 (q, 2 H), 1.34 (t, 3 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate; In tetrahydrofuran; water; at 80℃; for 16h; | Step E: l-Ethyl-4-(2-methyl-4-(((l S, 2S)-2-(5-methylpyridin-yl)cyclopropyl)methoxy) pyrimidin-5 -yl)pyridin-2( 1 H)-one A mixture of potassium trifluoro(2-methyl-4-(((lS,2S)-2-(5-methylpyridin-2- yl)cyclopropyl)methoxy)pyrimidin-5-yl)borate (100 mg, 0.28 mmol), 4-bromo-l-ethylpyridin- 2(lH)-one (67 mg, 0.33 mmol), [l,l'-bis(diphenylphosphino)ferrocene] dichloro-palladium(II) (23 mg, 0.03 mmol) and cesium carbonate (271 mg, 0.83 mmol) in THF (1.7 mL) and H2O (0.8 mL) was stirred at 80 C for 16 h. The mixture was cooled to ambient temperature, diluted with EtOAc (5 mL), washed with sodium bicarbonate (2 mL) and brine (2 mL), dried over MgS04, filtered and concentrated. The residue was purified by reverse phase chromatography (Waters Sunfire C18 OBD 5-80% methanol in water with 0.1% NH3- H20 modifer) to give the title compound as a colorless oil: LC/MS m/z = 377.19 [M+H]+; XH NMR (400 MHz, MeOD) delta 8.47 (s, 1 H), 8.18 (s, 1 H), 7.65 (d, 1 H), 7.51 (dd, 1 H), 7.15 (d, 1 H), 6.78 (d, 1 H), 6.67 (dd, 1 H), 4.58 (m, 1 H), 4.47 (m, 1 H), 4.11 - 4.02 (m, 2 H), 2.62 (s, 3 H), 2.29 (s, 3 H), 2.20 - 2.14 (m, 1 H), 1.89 - 1.80 (m, 1 H), 1.34 - 1.37 (t, 3 H), 1.28 - 1.23 (m, 1 H), 1.17 - 1.09 (m, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66.6% | With palladium diacetate; N-ethyl-N,N-diisopropylamine; tris-(o-tolyl)phosphine; In N,N-dimethyl-formamide; at 120℃; for 2h;Microwave irradiation; | (E)-Ethyl 3-(1 -ethyl-2-oxo-1 ,2-dihydropyridin-4-yl)acrylateTo a solution of 4-bromo-1-ethylpyridin-2(1 H)-one (285 mg, 1.41 1 mmol) in DMF (20 mL), ethyl acrylate (847 mg, 8.46 mmol), tri-o-tolylphosphine (129 mg, 0.423 mmol), N- ethyl-N-isopropylpropan-2-amine (729 mg, 5.64 mmol) and Pd(OAc)2(47.5 mg, 0.212 mmol) were added. The reaction mixture was heated in a microwave at 120 C for 2 h. Water was added to quench the reaction. EtOAc was added and the layers were separated. The aqueous layer was extracted once with EtOAc, and the combined organic layers were washed once with brine. The organic layer was concentrated. The crude product was then purified on a silica cartridge (40 g) with a Combiflash Companion, eluting at 40 mL/min with a gradient running from 100% CH2CI2s to 80% MeOH/CH2CI2over 35 min) to give 208 mg (66.6%) of the title compound. LC-MS m/z 221.9 (M+H)+, 0.71 (ret. time). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46.5% | With potassium carbonate; In N,N-dimethyl-formamide; at 70℃; for 4h; | 5-Bromo-1-ethylpyridin-2(1 H)-oneTo a solution of 5-bromo-2-methoxypyridine (600 mg, 3.19 mmol) in DMF (10 mL), iodoethane (747 mg, 4.79 mmol) and K2C03(1323 mg, 9.57 mmol) were added. The reaction was stirred at 70 C for 4 h. Then the solvent was evaporated. 20 mL of water was added to the residue, then it was adjusted to pH=8. EtOAc (3x30 mL) was extracted the water layer. The combined organic layer, dried with Mg2S04and cone, to get crude product. The crude product was then purified on a silica cartridge (40 g) with a Combiflash Companion, eluting at 40 mL/min with a gradient running from 100% CH2CI2to 80% MeOH/CH2CH2over 35 min) to give 300 mg (46.5%) of the title compound. LC-MS m/z 202.1 (M+H)+, 0.61 (ret. time). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | Under argon atmosphere, a solution of 4-bromo-1,2-dihydropyridin-2-one (1.00 g, 5.75 mmol) in THF (20 mL) was treated with sodium hydride (60% dispersion in mineral oil, 230 mg, 5.75 mmol) at 0C and then stirred 30 minutes at room temperature. Iodoethane (1.39 mL, 17.25 mmol) was added to the mixture and the reaction was stirred for 16 hours at room temperature and then heated at 50 C for 24 hours. The middle was diluted with water and ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (DCM/EtOAc 100/0 to 85/15) to give compound (150a) (981 mg, 4.86 mmol, 84%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris-(dibenzylideneacetone)dipalladium(0); potassium acetate; catacxium A; In N,N-dimethyl acetamide; at 90℃;Inert atmosphere; | A solution of compound (150a) (202 mg, 1.0 mmol), bis pinacol diboron (381 mg, 1.5 mmol) and potassium acetate (294 mg, 3 mmol) in N,N'-dimethylacetamide (0.7 mL) was degassed with argon for 10 minutes and tris(dibenzylideneacetone)dipalladium(0) (Pd2dba3, 9 mg, 0.01 mmol) and Di(1-adamantyl)-n-butylphosphine (11mg, 0.03 mmol) were then added. The mixture was heated at 90C overnight and then concentrated. The residue was diluted with ethyl acetate. The organic layer was washed with saturated solution of sodium bicarbonate, brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to give crude compound (150b) (800 mg) which was used in the next step without further purification. MS m/z ([M+H]+) 250. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With palladium bis[bis(diphenylphosphino)ferrocene] dichloride; caesium carbonate; In 1,4-dioxane; water; at 110℃; for 10h;Inert atmosphere; | General procedure: To a 50mL round-bottom flask under a nitrogen atmosphere 7 (10.0 mmol), bispinacolatodiboron (10.0 mmol), PdCl2(dppf)2 (0.5 mmol), potassium acetate (15 mmol) and 1, 4-dioxane (20 mL) were added. The reaction mixture was stirred at 80 C for 8 h. After the completion of the reaction, Cs2CO3 (15 mmol), PdCl2(dppf)2 (0.5 mmol), 3 (11.0 mmol) and 0.5 mL H2O were added to the above mixture. The reaction was stirred at 110 C overnight. After the completion of the reaction, 20 mL of H2O was added and the reaction mixture was extracted with DCM for 3 times. The combined organic layer was collected and rinsed with brine. The mixture was evaporated to obtain the crude product and purified by silica gel for 8a-8l. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | General procedure: To an ice-cold solution of 2-hydroxy-4-bromopyridine (5.75 mmol) in THF was added NaH (5.75 mmol) portion-wise. The reaction mixture was stirred in an ice-bath for 15 min followed by addition of halide or iodine (17.24 mmol). The resulting reaction mixturewas stirred at room temperature for 16 h. After the completion of the reaction, 20 mL of H2O was added and the reaction mixture was extracted with EtOAc 3 times. The combined organic layer was collected and rinsed with brine. The mixture was evaporated to obtain the crude product and purified by silica gel for 3a-3d. |