Structure of 905587-18-0
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CAS No. : | 905587-18-0 |
Formula : | C9H9FN2O |
M.W : | 180.18 |
SMILES Code : | CC(=O)NC(=C)C1=NC=C(F)C=C1 |
MDL No. : | MFCD18909366 |
* 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 |
---|---|---|
35% | N-( 1 -(5-Fluoropyridm-2-yl')vinyl')acetamide A solution of MeMgBr (170.3 ml, 510.98 mmol) in ether was diluted with 170 ml of anhydrous THF and cooled to 0 C. 5-Fluoropicolinontrile (Method 37, 53.6 g, 425.82 mmol) in THF (170 ml) was added dropwise. The reaction was stirred at 0 C for 30 minutes, then diluted with DCM (170 ml). Acetic anhydride (48.3 ml, 510.98 mmol) in DCM (100 ml) was added dropwise at 0 0C. After addition, the reaction was warmed to room temperature and stirred at room temperature for 8 hours. Saturated sodium bicarbonate solution (50 ml) was added and extracted with EtOAc (2 x 200 ml). The combined organic was dried over sodium sulfate. After removal of solvent, the resulted residue was purified by column chromatography (hexane-EtOAc = 2.5 : 1) to give the title compound as a white solid (26.6 g, 35%). 1H NMR (400 MHz) δ 9.37 (s, IH), 8.57 (d, J= 2.8 Hz, IH), 7.81 (m, 2H), 6.01 (s, IH), 5.52 (s, IH), 2.08 (s, 3H). MS: Calcd.: 180; Found: [M+H]+ 181 | |
35% | Intermediate 2: N-(1-(5-Fluoropyridin-2-yl)vinyl)acetamide. A solution of MeMgBr (170.3 ml, 510.98 mmol) in ether was diluted with 170 ml of anhydrous THF and cooled to 0 C. 5-Fluoropyridine-2-carbonitrile (Intermediate 1, 53.6 g, 425.82 mmol) in THF (170 ml) was added drop-wise. The reaction was stirred at 0 C for 30 minutes, then diluted with dichloromethane (170 ml). Acetic anhydride (48.3 ml, 510.98 mmol) in dichloromethane (100 ml) was added drop-wise at 0 0C. After addition, the reaction was warmed to room temperature and stirred at room temperature for 8 hours. Saturated sodium bicarbonate solution (50 ml) was added and extracted with EtOAc (2 x 200 ml). The combined organic was dried over sodium sulfate. After removal of solvent, the resulted residue was purified by column chromatography (hexane:EtOAc = 2.5 : 1) to give the title compound as a white solid (26.6 g, 35%). 1H NMR (400 MHz) δ 9.37 (s, 1 H), 8.57 (d, J= 2.8 Hz, 1 H), 7.81 (m, 2 H), 6.01 (s, 1 H), 5.52 (s, 1 H), 2.08 (s, 3 H). LCMS: 181 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | Intermediate 3A^-(l-(5-Fluoropyridin-2-yl)vinyl)acetamideA solution of MeMgBr (170.3 ml, 510.98 mmol) in ether was diluted with 170 ml of anhydrousTHF and cooled to 0 0C. 5-Fluoropyridine-2-carbonitrile (Intermediate 2, 53.6 g, 425.82 mmol) in THF (170 ml) was added dropwise. The reaction was stirred at 0 0C for 30 minutes, then diluted with DCM (170 ml). Acetic anhydride (48.3 ml, 510.98 mmol) in DCM (100 ml) was added drop- wise at 0 0C. After addition, the reaction was warmed to room temperature and stirred at room temperature for 8 hours. Saturated sodium bicarbonate solution (50 ml) was added and the product was extracted with EtOAc (2 x 200 ml). The combined organic was dried over sodium sulfate. After removal of solvent, the resulting residue was purified by column chromatography (hexane-EtOAc = 2.5 : 1) to give the title compound as a white solid (26.6 g,35%).1H NMR (400 MHz) δ: 9.37 (s, IH), 8.57 (d, IH), 7.81 (m, 2H), 6.01 (s, IH), 5.52 (s, IH), 2.08(s, 3H).LC-MS: 181 [M+H]. | |
35% | A solution of MeMgBr (170.3 ml, 510.98 mmol) in ether was diluted with 170 ml of anhydrousTHF and cooled to 0 0C. 5-Fluoropyridine-2-carbonitrile (Intermediate 19, 53.6 g, 425.82 mmol) in THF (170 ml) was added drop-wise. The reaction mixture was stirred at 0 0C for 30 minutes, then diluted with DCM (170 ml). Acetic anhydride (48.3 ml, 510.98 mmol) in DCM(100 ml) was added drop-wise at 0 0C. After the addition, the reaction mixture was warmed to room temperature and stirred at room temperature for 8 hours. Saturated sodium bicarbonate solution (50 ml) was added and extracted with EtOAc (2 x 200 ml). The combined organic was dried over sodium sulfate. After removal of solvent, the resulted residue was purified by column chromatography (hexane-EtOAc = 2.5 : 1) to give the title compound as a white solid (26.6 g,35%).1H NMR (400 MHz) δ: 9.37 (s, IH), 8.57 (d, IH), 7.81 (m, 2H), 6.01 (s, IH), 5.52 (s, IH), 2.08(s, 3H).LC-MS: 181 [M+H]+. | |
35% | A solution of MeMgBr (170.3 ml, 510.98 mmol) in ether was diluted with 170 ml of anhydrous THF and cooled to 0 0C. 5-Fluoropyridine-2-carbonitrile (Intermediate 11, 53.6 g, 425.82 mmol) in THF (170 ml) was added dropwise. The reaction mixture was stirred at 0 0C for 30 minutes, then diluted with DCM (170 ml). Acetic anhydride (48.3 ml, 510.98 mmol) in DCM (100 ml) was added dropwise at 0 0C. After the addition, the reaction mixture was warmed to room temperature and stirred at room temperature for 8 hours. Saturated sodium bicarbonate solution (50 ml) was added and an extraction was carried out with EtOAc (2 x 200 ml). The combined organic layers were dried over sodium sulfate. After removal of solvent, the resulting residue was purified by column chromatography (hexane:EtOAc = 2.5 : 1), providing the title compound as a white solid (26.6 g, 35%). 1H νMR (400 MHz) δ: 9.37 (s, IH), 8.57 (d, J= 2.8 Hz, IH), 7.81 (m, 2H), 6.01 (s, IH), 5.52 (s, IH), 2.08 (s, 3H). |
35% | Intermediate 4N-( 1 -(5-Fluoropyridin-2-yl)vinyl)acetamide; A solution of MeMgBr (170.3 ml, 510.98 mmol) in ether was diluted with 170 ml of anhydrous THF and cooled to 0 0C. 5-Fluoropyridine-2-carbonitrile (Intermediate 3, 53.6 g, 425.82 mmol) in THF (170 ml) was added dropwise. The reaction was stirred at 0 0C for 30 minutes, then diluted with DCM (170 ml). Acetic anhydride (48.3 ml, 510.98 mmol) in DCM (100 ml) was added dropwise at 0 0C. After addition, the reaction was warmed to room temperature and stirred at room temperature for 8 hours. Saturated sodium bicarbonate solution (50 ml) was added and extracted with EtOAc (2 x 200 ml). The combined organic was dried over sodium sulfate. After removal of solvent, the resulted residue was purified by column chromatography (hexane : EtOAc = 2.5 : 1) to give the title compound as a white solid (26.6 g, 35%). 1H NMR (400 MHz) δ 9.37 (s, IH), 8.57 (d, J= 2.8 Hz, IH), 7.81 (m, 2H), 6.01 (s, IH), 5.52 (s, IH), 2.08 (s, 3H). MS: Calculated: 180; Found: [M+H]+ 181. | |
35% | Intermediate 12N-ri-(5-Fluoropyridin-2-yl)vinvHacetamideA solution of MeMgBr (170.3 ml, 510.98 mmol) in ether was diluted with 170 ml of anhydrous THF and cooled to 0 0C. 5-Fluoropyridine-2-carbonitrile (Intermediate 11, 53.6 g, 425.82 mmol) in THF (170 ml) was added dropwise. The reaction was stirred at 0 0C for 30 minutes, then diluted with DCM (170 ml). Acetic anhydride (48.3 ml, 510.98 mmol) in DCM (100 ml) was added drop-wise at 0 0C. After addition, the reaction was warmed to room temperature and stirred at room temperature for 8 hours. Saturated sodium bicarbonate solution (50 ml) was added and extracted with EtOAc (2 x 200 ml). The combined organic was dried over sodium sulfate. After removal of solvent, the resulted residue was purified by column chromatography (hexane : EtOAc = 2.5 : 1) to give the title compound as a white solid (26.6 g, 35%). 1H NMR (400 MHz) δ: 9.37 (s, IH), 8.57 (d, IH), 7.81 (m, 2H), 6.01 (s, IH), 5.52 (s, IH), 2.08 (s, 3H). LCMS: 181 [M+H]. | |
35% | Intermediate 2N-( 1 -(5-Fluoropyridin-2-yl)vinyl)acetamide; A solution of MeMgBr (170.3 ml, 510.98 mmol) in ether was diluted with 170 ml of anhydrous THF and cooled to 0 ºC. 5-fluoropyridine-2-carbonitrile (Intermediate 1, 53.6 g, 425.82 mmol) in THF (170 ml) was added dropwise. The reaction was stirred at 0 C for 30 minutes, then diluted with dichloromethane (170 ml). Acetic anhydride (48.3 ml, 510.98 mmol) in dichloromethane (100 ml) was added dropwise at 0 ºC. After addition, the reaction was warmed to room temperature and stirred at room temperature for 8 hours. Saturated sodium bicarbonate solution (50 ml) was added and extracted with EtOAc (2 x 200 ml). The combined organic was dried over sodium sulfate. After removal of solvent, the resulted residue was purified by column chromatography (hexane : EtOAc = 2.5 : 1) to give the title compound as a white solid (26.6 g, 35%). 1H NMR (400 MHz) δ 9.37 (s, 1 H), 8.57 (d, J= 2.8 Hz, 1 H), 7.81 (m, 2 H), 6.01 (s, 1 H), 5.52 (s, 1 H), 2.08 (s, 3 H). MS: Calculated: 180; Found: [M+H]+ 181. | |
35% | A solution of MeMgBr (170.3 ml, 510.98 mmol) in ether was diluted with 170 ml of anhydrous THF and cooled to 0 C. 5-Fluoropicolinontrile (Method 35; 53.6 g, 425.82 mmol) in THF (170 ml) was added dropwise. The reaction was stirred at 0 0C for 30 minutes, then diluted with DCM (170 ml). Acetic anhydride (48.3 ml, 510.98 mmol) in DCM (100 ml) was added dropwise at 0 C. After addition, the reaction was warmed to room temperature and stirred at room temperature for 8 hrs. Saturated sodium bicarbonate solution (50 ml) was added and extracted with EtOAc (2 x 200 ml). The combined organic was dried over sodium sulfate. After removal of solvent, the resulted residue was purified by column chromatography (hexane-EtOAc = 2.5 : 1) to give the title compound as a white solid (26.6 g, 35%). 1H NMR (400 MHz) δ 9.37 (s, IH), 8.57 (d, J= 2.8 Hz, IH), 7.81 (m, 2H), 6.01 (s, IH), 5.52 (s, IH), 2.08 (s, 3H). MS: Calcd.: 180; Found: [M+H]+ 181. | |
31% | PREPARATION 32 (R)-1-(5-Fluoropyridin-2-yl)ethanamine hydrochloride [Show Image]a) N-(1-(5-Fluoropyridin-2-yl)vinyl)acetamide: 5-Fluoropicolinonitrile (9.30 g, 76.2 mmol) in tetrahydrofuran (40 mL) was added dropwise to a cold (0 C), stirred solution of methylmagnesium bromide (3M in diethylether, 30.47 mL, 91.4 mmol) in tetrahydrofuran (40 mL). The mixture was stirred for 30 minutes at 0 C then diluted with dichloromethane (30 mL) and then acetic anhydride (8.64 mL, 91.4 mmol) in dichloromethane (2 mL) was added dropwise at 0 C. The mixture was warmed to room temperature and stirred overnight. 4% Aqueous sodium hydrogen carbonate solution was added and the mixture was extracted with ethyl acetate. The organic layer was dried (MgSO4), evaporated and the residue was purified by flash chromatography (3:1 hexanes/ethyl acetate) to give the title compound (4.30 g, 31%) as a yellow solid. LRMS (m/z): 181 (M+1)+.1H NMR (300 MHz, CDCl3) δ ppm 2.21 (s, 3H), 5.47 (s, 1H), 6.47 (s, 1H), 7.48 (m, 1H), 7.78 (m, 1H), 8.37 (m, 1H), 9.07 (br s, 1H). | |
31% | PREPARATION 32 (R)-1-(5-Fluoropyridin-2-yl)ethanamine hydrochloride a) N-(1-(5-Fluoropyridin-2-yl)vinyl)acetamide: 5-Fluoropicolinonitrile (9.30 g, 76.2 mmol) in tetrahydrofuran (40 mL) was added dropwise to a cold (0 C), stirred solution of methylmagnesium bromide (3M in diethylether, 30.47 mL, 91.4 mmol) in tetrahydrofuran (40 mL). The mixture was stirred for 30 minutes at 0 C then diluted with dichloromethane (30 mL) and then acetic anhydride (8.64 mL, 91.4 mmol) in dichloromethane (2 mL) was added dropwise at 0 C. The mixture was warmed to room temperature and stirred overnight. 4% Aqueous sodium hydrogen carbonate solution was added and the mixture was extracted with ethyl acetate. The organic layer was dried (MgSO4), evaporated and the residue was purified by flash chromatography (3:1 hexanes/ethyl acetate) to give the title compound (4.30 g, 31%) as a yellow solid. LRMS (m/z): 181 (M+1)+.1H NMR (300 MHz, CDCl3) δ ppm 2.21 (s, 3H), 5.47 (s, 1H), 6.47 (s, 1H), 7.48 (m, 1H), 7.78 (m, 1H), 8.37 (m, 1H), 9.07 (br s, 1H). | |
31% | a) N-(1-(5-Fluoropyridin-2-yl)vinyl)acetamide A solution of <strong>[327056-62-2]5-fluoropicolinonitrile</strong> (9.30 g, 76.2 mmol) in tetrahydrofuran (40 mL) was added dropwise to a cold (0 C), stirred solution of methylmagnesium bromide (3M solution in diethylether, 30.47 mL, 91.4 mmol) in tetrahydrofuran (40 mL). The mixture was stirred for 30 minutes at 0 C then diluted with dichloromethane (30 mL) and then acetic anhydride (8.64 mL, 91.4 mmol) in dichloromethane (2 mL) was added dropwise at 0 C. The mixture was warmed to ambient temperature and stirred overnight. 4% Aqueous sodium hydrogencarbonate solution was added and the mixture was extracted with ethyl acetate. The organic layer was separated, dried (MgSO4) evaporated and the residue was purified by flash chromatography (3:1 hexanes/ethyl acetate) to give the title compound (4.30 g, 31 %) as a yellow solid. LRMS (m/z): 181 (M+1)+. 1H NMR δ (300 MHz, CDCl3): 2.21 (s, 3H), 5.47 (s, 1H), 6.47 (s, 1H), 7.48 (m, 1H), 7.78 (m, 1H), 8.37 (m, 1H), 9.07 (br s, 1H). | |
a) yV-(1 -(5-Fluoropyridin-2-yl)vinyl)acetamideA solution of <strong>[327056-62-2]5-fluoropicolinonitrile</strong> (9.30 g, 76.2 mmol) in tetrahydrofuran (40 mL) was added dropwise to a cold (0 C), stirred solution of methylmagnesium bromide (3M solution in diethyl ether, 30.47 mL, 91 .4 mmol) in tetrahydrofuran (40 mL). The mixture was stirred for 30 minutes at 0 C then diluted with dichloromethane (30 mL) and then acetic anhydride (8.64 mL, 91 .4 mmol) in dichloromethane (2 mL) was added dropwise at 0 C. The mixture was warmed to ambient temperature and stirred overnight. 4% Aqueous sodium hydrogencarbonate solution was added and the mixture was extracted with ethyl acetate. The organic layer was separated, dried (MgS04), evaporated and the residue was purified by flash chromatography (3:1 hexanes/ethyl acetate) to give the title compound (4.30 g, 31 %) as a yellow solid.LRMS (m/z): 181 (M+1 )+.1H NMR δ (300 MHz, CDCI3): 2.21 (s, 3H), 5.47 (s, 1 H), 6.47 (s, 1 H), 7.48 (m, 1 H), 7.78 (m, 1 H), 8.37 (m, 1 H), 9.07 (br s, 1 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A solution of <strong>[327056-62-2]5-fluoropicolinonitrile</strong> (Method 35; 1875g 1 equivalent) in THF (3.7 volumes) was added to methyl magnesium chloride (3N in THF, 1.2 equivalents) maintaining the temperature at O0C. The reaction mixture was stirred for 30 minutes at O0C and then EPO <DP n="64"/>diluted with DCM (3.2 volumes) at O0C. Acetic anhydride (2.0 equivalents) in DCM (1.6 volumes.) was added at a rate to maintain the temperature at O0C. The batch was allowed to warm to room temperature and stirred overnight. Saturated, aqueous sodium hydrogen carbonate (13.9 volumes) was added and the product was extracted into EtOAc (1 x 0.53 volumes, 1 x 0.26 volumes). The combined extracts were dried, filtered and evaporated in vacuo and purification carried out by chromatography (5 w/w silica; 20-100 % DCM in hexane). The mixture of N-mono and N,N-di-acetylated compounds was treated with potassium carbonate (0.1 w/w on mixture) in methanol (5 volumes) for 30 minutes. The inorganic solids were filtered and washed with methanol. Silica was added to the methanol solution to remove residual potassium carbonate prior to evaporation. The product, pre- adsorbed on silica, was eluted through a silica pad (2 w/w silica; 90-100 % DCM in hexane) and evaporated to give an orange solid. Mp 61.0 - 62.20C, 636g, 23.0% theory. |