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Structure of Diethyl cyanophosphonate
CAS No.: 2942-58-7
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CAS No. : | 2942-58-7 |
Formula : | C5H10NO3P |
M.W : | 163.11 |
SMILES Code : | O=P(OCC)(C#N)OCC |
MDL No. : | MFCD00010256 |
InChI Key : | ZWWWLCMDTZFSOO-UHFFFAOYSA-N |
Pubchem ID : | 76257 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H300+H310+H330-H314 |
Precautionary Statements: | P260-P264-P280-P284-P301+P310-P302+P350 |
Class: | 8(6.1) |
UN#: | 2922 |
Packing Group: | Ⅱ |
* 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 |
---|---|---|
With triethylamine; | EXAMPLE 88 Ethyl 2-(4-isopropylphenoxy)-3-[4-[2-(4'-methoxybiphenyl-4-carbonylamino)ethoxy]phenyl]propionate (ethyl ester of exemplification No. 7-179 compound) In a similar manner to that described in Example 73, a reaction was carried out using ethyl 3-[4-(2-t-butoxycarbonylaminoethoxy)phenyl]-2-(4-isopropylphenoxy)propionate (723 mg), which is the product of Reference example 25, 4'-methoxybiphenyl-4-carboxylic acid (350 mg), diethyl cyanophosphonate (0.25 ml) and triethylamine (0.47 ml) and the reaction mixture was treated to give the title compound (600 mg) as a white powder. mp 116-117 C. 1H-NMR (270 MHz, CDCl3): δ ppm 1.18 (6H, d, J=7.0 Hz), 1.20 (3H, t, J=7.0 Hz), 2.82 (1H, septet, J=7.0 Hz), 3.15-3.21 (2H, m), 3.86 (3H, s), 3.86-3.91 (2H, m), 4.14 (2H, t, J=5.0 Hz), 4.18 (2H, q, J=7.0 Hz), 4.69 (1H, dd, J=6.0, 7.0 Hz), 6.62 (1H, t, J=5.0 Hz), 6.76 (2H, d, J=8.5 Hz), 6.86 (2H, d, J=8.5 Hz), 6.99 (2H, d, J=8.5 Hz), 7.08 (2H, d, J=8.5 Hz), 7.23 (2H, d, J=8.5 Hz), 7.55 (2H, d, J=8.5 Hz), 7.61 (2H, d, J=8.0 Hz), 7.83 (2H, d, J=8.0 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; | g) Synthesis of 1-(5,7-dihydro-4H-thieno[2,3-c]pyridin-6-yl)-6-phenylhexan-1-one To a solution of 0.272 g (1.548 mmol) of <strong>[28783-38-2]4,5,6,7-tetrahydrothieno[2,3-c]pyridine hydrochloride</strong>, 0.33 g (1.7 mmol) of 6-phenylhexanoic acid and 0.86 ml (6.2 mmol) of triethylamine in 30 ml of dichloromethane, 0.28 ml (1.9 mmol) of diethyl cyanophosphonate was added dropwise under ice-cooling, followed by overnight stirring at room temperature. The reaction mixture was poured into aqueous sodium hydroxide and extracted with dichloromethane 3 times. The combined organic layer was dried over anhydrous magnesium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate=6/1 to 3/1) to yield the desired product. Colorless oil Yield 0.503 g (100%) 1 H-NMR (CDCl3, 200 MHz) delta1.340-1.478 (2H, m), 1.577-1.789 (4H, m), 2.340-2.450 (2H, m), 2.573-2.786 (4H, m), 3.690 (1.2H, t, J=5.7 Hz), 3.868 (0.8H, t, J=5.8 Hz), 4.654 (0.8H, s), 4.800 (1.2H, s), 6.775-6.821 (1H, m), 7.134-7.314 (6H, m); IR (neat) 2929, 1645, 1427, 1227, 702 cm-1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; | a) Synthesis of 6-(anthraquinone-2-carbonyl)-4,5,6,7-tetrahydrofuro[2,3-c]pyridine To a solution of 0.160 g (1.000 mmol) of 4,5,6,7-tetrahydrofuro[2,3-c]pyridine hydrochloride, 0.302 g (1.2 mmol) of <strong>[117-78-2]anthraquinone-2-carboxylic acid</strong> and 0.55 ml (4.0 mmol) of triethylamine in 30 ml of dichloromethane, 0.24 g (1.5 mmol) of diethyl cyanophosphonate was added under ice-cooling, followed by overnight stirring at room temperature. The reaction mixture was poured into water and extracted with dichloromethane 2 times. The combined organic layer was washed with water and dried over anhydrous sodium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate=3/1 to 2/1); the resulting solid was washed with ethyl acetate to yield the desired product. Pale green crystal Yield 0.292 g (82percent) 1 H-NMR (CDCl3, 200 MHz) delta2.613-2.618 (2H, m), 3.580-3.603 (1.2H, m), 4.000-4.040 (0.8H, m), 4.458-4.462 (0.8H, m), 4.818 (1.2H, s), 6.295 (1H,d, J=1.8 Hz), 7.363 (1H, s), 7.817-7.908 (3H, m), 8.311-8.421 (4H, m); IR (KBr) 1645, 1437, 1323, 1296, 710 cm-1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; | a) Synthesis of 5-(anthraquinone-2-carbonyl)-4,5,6,7-tetrahydrofuro[3,2-c]pyridine To a solution of 0.160 g (1.000 mmol) of 4,5,6,7-tetrahydrofuro[3,2-c]pyridine hydrochloride, 0.302 g (1.2 mmol) of <strong>[117-78-2]anthraquinone-2-carboxylic acid</strong> and 0.55 ml (4.0 mmol) of triethylamine in 30 ml of dichloromethane, 0.24 g (1.5 mmol) of diethyl cyanophosphonate was added under ice-cooling, followed by overnight stirring at room temperature. The reaction mixture was poured into water and extracted with dichloromethane 2 times. The combined organic layer was washed with water and dried over anhydrous sodium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel chromatography (hexane/ethyl acetate=2/1); the resulting solid was washed with ethyl acetate to yield the desired product. Yellow crystal Yield 0.229 g (64percent) 1 H-NMR (CDCl3, 200 MHz) delta2.791-2.888 (2H, m), 3.652-3.678 (1H, m), 4.123 (1H, s), 4.363 (1H, s), 4.714 (1H, s), 6.088 (0.5H, s), 6.332 (0.5H, s), 7.290 (0.5H, s), 7.350 (0.5H, s), 7.812-7.903 (3H, m), 8.304-8.412 (4H, m); IR (KBr) 1676, 1632, 1439, 1323, 1296, 710 cm-1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; citric acid; In N-methyl-acetamide; | b) 5(S)-Tert-butoxycarbonylamino-4(S)-tert-butyldimethylsilyloxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid [N-(3-carbamoyl-propyl)]-amide 67 mul of triethylamine, 34 mg of <strong>[13031-62-4]4-aminobutyric acid amide hydrochloride</strong> and 38 mul of cyanophosphonic acid diethyl ester are added in succession to 128 mg of 5(S)-tert-butoxycarbonylamino-4(S)-tert-butyldimethylsilyloxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxy-propyloxy)-phenyl]-octanoic acid in 8 ml of dimethylformamide at 0 C. The reaction mixture is stirred for a further 18 hours at room temperature. The reaction mixture is concentrated by evaporation and 20 ml of 10% citric acid solution and ice are added to the residue. The mixture is extracted repeatedly with ethyl acetate and the organic phases are then washed with saturated sodium hydrogen carbonate solution and saturated sodium chloride solution. After concentration by evaporation, the residue is purified by means of FC (70 g of silica gel, dichloromethane/methanol=9:1). The title compound is obtained: Rf (dichloromethane/methanol=9:1)=0.38. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | With sodium chloride; sodium hydrogencarbonate; triethylamine; In N-methyl-acetamide; | EXAMPLE 13 N-[4-(4-piperidinomethyl-2-pyridyloxy)-cis-2-butenyl]pyrazole-4-carboxamide A solution of 2.39 g of 4-(4-piperidinomethyl-2-pyridyloxy) -cis-2-butenylamine and 1.08 g of <strong>[37718-11-9]4-pyrazolecarboxylic acid</strong> in 40 ml of dry dimethylformamide was stirred for 5 minutes, whilst ice-cooling. 1.89 g of diethyl cyanophosphonate and 1.65 ml of triethylamine were added to the mixture, and the resulting mixture was stirred at room temperature for 3 hours. At the end of this time, the reaction mixture was diluted with water and extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium hydrogencarbonate and then with a saturated aqueous solution of sodium chloride, after which it was dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure, and the residue was purified by column chromatography through silica gel, using a 1:9 by volume mixture of methanol and chloroform as the eluent, to give 1.65 g (yield 51percent) of the title compound as a white powder, melting at 121°-123° C. Nuclear Magnetic Resonance Spectrum (CDCl3), delta ppm: 1.38-1.52 (2H, multiplet); 1.52-1.66 (4H, multiplet); 2.32-2.48 (4H, multiplet); 3.42 (2H, singlet); 4.16 (2H, triplet, J=5.6 Hz); 4.95 (2H, doublet, J=5.9 Hz); 5.72-5.96 (2H, multiplet); 6.74 (1H, singlet); 6.81 (1H, broad triplet, J=5.6 Hz); 6.87 (1H, doublet, J=5.3 Hz); 7.99 (2H, singlet); 8.03 (1H, doublet, J=5.3 Hz). Infrared Absorption Spectrum (KBr), numax cm-1: 2933, 1629, 1611, 1566, 1530, 1408, 1342, 1299. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With sodium chloride; sodium hydrogencarbonate; triethylamine; In N-methyl-acetamide; | EXAMPLE 64 N-[3-(4-Piperidinomethyl-2-pyridyloxy)propyl]-pyrazole-4-carboxamide A solution of 1.0 g of 3-(4-piperidinomethyl-2-pyridyloxy)propylamine and 0.45 g of <strong>[37718-11-9]4-pyrazolecarboxylic acid</strong> dissolved in 15 ml of dimethylformamide was stirred for 5 minutes, whilst ice-cooling, after which 734 mg of diethyl cyanophosphonate and 0.68 ml of triethylamine were added to the resulting mixture. The mixture was then stirred at room temperature for 3 hours, after which it was diluted with water, and the aqueous mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium hydrogencarbonate and then with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure, and the resulting residue was purified by column chromatography through silica gel, using a 1:9 by volume mixture of methanol and chloroform as the eluent, to give 1.2 g (yield 85%) of the title compound as a white powder, melting at 117-119 C. Nuclear Magnetic Resonance Spectrum (CDCl3), delta ppm: 1.39-1.47 (2H, multiplet); 1.50-1.62 (4H, multiplet); 1.99-2.11 (2H, multiplet); 2.34-2.44 (4H, multiplet); 3.41 (2H, singlet); 3.55 (2H, quartet, J=5.9 Hz); 4.42 (2H, triplet, J=5.9 Hz); 6.72 (1H, singlet); 6.88 (1H, doublet, J=5.3 Hz); 7.16 (2H, broad triplet, J=5.9 Hz); 7.99-8.05 (2H, multiplet); 8.05 (1H, doublet, J=5.3 Hz). Infrared Absorption Spectrum (KBr), numax cm-1: 3250, 2935, 1631, 1607, 1566, 1421, 1386, 1302, 1212. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In N,N-dimethyl-formamide; | WORKING EXAMPLE 52 To a mixture of 2-methoxymethyl-4-(3,4,5trimethoxybenzoyl)piperazine hydrochloride obtained in Reference Example 6 (0.52 g), <strong>[39067-29-3]2-(3-pyridyl)thiazol-4-carboxylic acid</strong> (0.3 g), triethylamine (0.46 g) and N,N-dimethylformamide (3 ml) is added dropwise, while stirring under icecooling, diethyl cyanophosphonate (0.47 g). The reaction mixture is stirred at 0 C. for one hour, and then poured into ice-water, followed by extraction with ethyl acetate. The organic layer is washed with water, dried and concentrated under reduced pressure. The concentrate is purified by means of a silica gel column chromatography (eluent:AcOEt-CH2 Cl2 --CH3 OH=10:9:1) to give 2-methoxymethyl-1-[2-(3-pyridyl) thiazol-4-ylcarbonyl]-4-(3,4,5-trimethoxybenzoyl) piperazine. Recrystallization from ethanol gives colorless needles m.p. 149-150 C. Elemental analysis for C25 H28 N4 O6 S*1/3H2 O: Calcd.: C 57.90; H, 5.57; N, 10.80: Found: C 58.12; H, 5.52; N, 10 86: | |
With triethylamine; In N,N-dimethyl-formamide; | Working Example 52 To a mixture of 2-methoxymethyl-4-(3,4,5-trimethoxybenzoyl)piperazine·hydrochloride obtained in Reference Example 6 (0.52 g), <strong>[39067-29-3]2-(3-pyridyl)thiazol-4-carboxylic acid</strong> (0.3 g), triethylamine (0.46 g) and N,N-dimethylformamide (3 ml) is added dropwise, while stirring under icecooling, diethyl cyanophosphonate (0.47 g). The reaction mixture is stirred at 0C for one hour, and then poured into ice-water, followed by extraction with ethyl acetate. The organic layer is washed with water, dried and concentrated under reduced pressure. The concentrate is purified by means of a silica gel column chromatography (eluent: AcOEt-CH2Cl2-CH3OH = 10:9:1) to give 2-methoxymethyl-1-[2-(3-pyridyl)thiazol-4-ylcarbonyl]-4-(3,4,5-trimethoxybenzoyl)piperazine. Recrystallization from ethanol gives colorless needles m.p. 149-150C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In N-methyl-acetamide; | EXAMPLE 13 Compound 87 Dry triethylamine (3.24 g) was added at 0-5 C. to a stirred solution of diethyl cyanophosphate (1.96 g), 4-trifluoromethylbenzoic acid (2.28 g) and <strong>[50607-30-2]piperidine-2,4-dione</strong> (1.13 g) in dry dimethylformamide (50 ml) and the mixture stirred at ambient temperature for 5 hours. The mixture was diluted with dichloromethane (70 ml) and the solution washed successively with 2N hydrochloric acid (70 ml) and water (5*30 ml). The dichloromethane solution was dried over magnesium sulphate and evaporated under reduced pressure to give a brown solid which was recrystallized from toluene (11 ml) to give 3-(4-trifluoromethylbenzoyl)<strong>[50607-30-2]piperidine-2,4-dione</strong> (0.44 g), mp 197-200 C., as a pale green crystalline solid. |