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CAS No. : | 42822-57-1 | MDL No. : | MFCD00272195 |
Formula : | C10H16NO3P | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | OIGQTUBEBRLSOX-UHFFFAOYSA-N |
M.W : | 229.21 | Pubchem ID : | 273213 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338-P310 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H332-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
88% | With stannous chloride; In dichloromethane; | (4-Amino-phenyl)-phosphonic Acid Diethyl Ester: (4-Nitro-phenyl)-phosphonic acid diethyl ester (7.6 g, 29.1 mmol) and SnCl2 (29.6 g, 0.13 mmol) were heated at reflux for 1 h. The mixture was poured in CH2Cl2 (500 mL) and adjusted to pH 8 with sat'd Na2CO3. The resulting mixture was filtered through Celite (CH2Cl2 wash) and the layers separated. The aqueous layer was extracted with CH2Cl2 and the combined extracts, were washed with water, sat'd NaCl, then dried over MgSO4 and filtered. Concentration yielded a light yellow solid (5.9 g, 88%): MS [M+H]+230; m.p. 117-118 C. |
85% | With formic acid; triethylamine;1% Pd/C; at 20℃;Reflux; | Into a 50-mL round-bottom flask, was placed a solution of diethyl 4-mtrophenylphosphonate (1 07 g, 4 13 mmol, 1 00 equiv), TEA (3 mL), Palladium carbon (0 025 g) This was followed by the addition of formic acid (2 mL) dropwise with stirring at room temperature The resulting solution was heated to reflux for 3 hr The reaction was then quenched by the addition of 5 mL of water and the solids were filtered out The resulting filtrate was extracted with 5x10 mL of dichloromethane and the organic layers combined and d?ed over anhydrous sodium sulfate This resulted in 800 mg (85%) of diethyl 4- ammophenylphosphonate as a white solid. |
1.2 g | With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃; for 14h; | Diethyl 4-nitrophenylphosphonate (1.700 g, containing ca. 14% diethyl phosphite) was dissolved in methanol (20 ml) and was stirred in the presence of Pd (10% on carbon, 0.100 g) under H2 (balloon) at room temperature for 14 h. The Pd/C was filtered through a pad of celite. The filtrate was concentrated to dryness affording the title compound 13a (1.200 g, 80%) as a brown solid. 1H NMR (400 MHz, CDCl3) delta 7.63- 7.54 (m, 2H), 6.76-6.70 (m, 2H), 4.16-3.96 (m, 4H), 3.81 (br s, 2H), 1.30 (2t, J= 7.5Hz, 6H). LC-MS (ESI+) m/z 174.04 (M+H-2 C2H4)+; HRMS (ESI+) m/z calculated for C10H17NO3P (M+H)+ 230.0941 , found 230.0936. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With potassium carbonate; In tetrahydrofuran; dichloromethane; N,N-dimethyl-formamide; | EXAMPLE 23 To a solution of 7,8-dimethoxy-5-oxo-1,2,4,5-tetrahydro-3-benzothiepine-2-carboxylic acid (0.9 g) in tetrahydrofuran (THF) (30 ml) were added oxalyl chloride (0.445 g) and DMF (one drop) successively. The reaction mixture was stirred for 3 hours at room temperature and concentrated under reduced pressure. The residual oil was dissolved in dichloromethane (10 ml). The solution was added dropwise to a mixture of <strong>[42822-57-1]diethyl 4-aminophenylphosphonate</strong> (0.733 g), potassium carbonate (3 g) and dichloromethane (30 ml) at room temperature, followed by stirring for 30 minutes at room temperature. The reaction mixture was washed successively with water, 2N--HCl and water and dried (MgSO4). The solvent was distilled off under reduced pressure to obtain N-(4-diethoxyphosphorylphenyl)-7,8-dimethoxy-5-oxo-1,2,4,5-tetrahydro-3-benzothiepine-2-carboxamide (1.25 g, 78%) as crystals. Recrystallization from ethyl acetate-hexane gave colorless prisms. mp: 171-172 C. |
78% | With potassium carbonate; In tetrahydrofuran; dichloromethane; N,N-dimethyl-formamide; | Example 23 To a solution of 7,8-dimethoxy-5-oxo-1,2,4,5-tetrahydro-3-benzothiepine-2-carboxylic acid (0.9 g) in tetrahydrofuran (THF) (30 ml) were added oxalyl chloride (0.445 g) and DMF (one drop) successively. The reaction mixture was stirred for 3 hours at room temperature and concentrated under reduced pressure. The residual oil was dissolved in dichloromethane (10 ml). The solution was added dropwise to a mixture of <strong>[42822-57-1]diethyl 4-aminophenylphosphonate</strong> (0.733 g), potassium carbonate (3 g) and dichloromethane (30 ml) at room temperature, followed by stirring for 30 minutes at room temperature. The reaction mixture was washed successively with water, 2N-HCl and water and dried (MgSO4). The solvent was distilled off under reduced pressure to obtain N-(4-diethoxyphosphorylphenyl)-7,8-dimethoxy-5-oxo-1,2,4,5-tetrahydro-3-benzothiepine-2-carboxamide (1.25 g, 78%) as crystals. Recrystallization from ethyl acetate - hexane gave colorless prisms. mp: 171 - 172C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With thionyl chloride; In pyridine; dichloromethane; | EXAMPLE 56 A mixture of 7-cyclohexyl-1,2,4,5-tetrahydro-3-benzothiepin-5-one-2-carboxylic acid (1.0 g) and thionyl chloride (2 ml) was heated under reflux for 30 minutes and, then, concentrated. The residual oil was dissolved in dichloromethane (5 ml). This solution was added dropwise to a solution of 4-diethoxyphosphorylaniline (757 mg) in pyridine (10 ml) at room temperature. After stirring for 30 minutes at room temperature, the reaction mixture was concentrated. The residue was diluted with 1N-HCl (50 ml) and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4) and the solvent was distilled off to give 7-cyclohexyl-N-(4-diethoxyphosphorylphenyl)-1,2,4,5-tetrahydro-3-benzothiepin-5-one-2-carboxamide (760 mg, yield 45%). Recrystallization from ethanol gave colorless prisms. m.p. 222-223 C. Elemental analysis: C27 H34 NO5 PS Calcd.: C, 62.90; H, 6.65; N, 2.72. Found: C, 62.79; H, 6.55; N, 2.71. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | To a mixture of 4-(4-chlorophenyl)-2-phenyl-5-oxazolepropionic acid (500 mg), triethylamine (230 mg) and tetrahydrofuran (10 ml) was added ethyl chlorocarbonate (250 mg) at -40C, and the mixture was stirred for 1 hr. Diethyl 4-aminophenylphosphonate (420 mg) was added, and the mixture was stirred at room temperature for 5 hrs. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography and 3-[4-(4-chlorophenyl)-2-phenyl-5-oxazolyl]-N-[4-(diethylphosphono)phenyl]propionamide (295 mg, yield 36%) was obtained as colorless prism crystals from a fraction eluted with ethyl acetate-chloroform (1:1, volume ratio). melting point: 139-140C (recrystallized from dichloromethane-isopropyl ether). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26% | To diethyl 4-ammophenylphosphonate (intermediate 2 2) (150 mg, 0 66 mmol, 1 00 eqmv) m pyridine (3 mL) was added Intermediate 51 2 (300 mg, 0 77 mmol, 1 22 eqmv) in several portions The mixture was stirred for 3 h at 3O0C and then concentrated, the pH value of the solution adjusted to 3 with aqueous HCl (1 mol/L) and the resulting mixture extracted with 3x30 mL of ethyl acetate The organic layers were combined, dried over anhydrous sodium sulfate, concentrated, applied onto a silica gel column and eluted with dichloromethane methanol (50 1) to afford 100 mg (26%) of Intermediate 51 3 as a yellowish solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
EXAMPLE 32 diethyl [4-(3-{5-fluoro-2-[3-(4-fluoro-3-trifluoromethylphenyl)-5,5-dimethyl-2,4-dioxoimidazolidin-1-ylmethyl]phenyl}ureido)phenyl]phosphonate To 0.74 ml of a solution of phosgene in toluene (20%) was slowly added dropwise, under argon at 75 C., 0.29 g of compound 23.3, dissolved in 10 ml of dry acetonitrile. After the addition had ended, the mixture was stirred at 80 C. for 2 h. Thereafter, the reaction mixture was concentrated under reduced pressure, and the residue was admixed with toluene and concentrated again under reduced pressure. The residue was dissolved in 10 ml of dry tetrahydrofuran and admixed with 0.16 g of <strong>[42822-57-1]diethyl 4-aminophenylphosphonate</strong>. To this mixture was slowly added dropwise 0.15 ml of triethylamine. Subsequently, the mixture was stirred at room temperature for 4 h and then left to stand at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the residue was purified by chromatography (method [RP1]). This afforded diethyl [4-(3-{5-fluoro-2-[3-(4-fluoro-3-trifluoromethylphenyl)-5,5-dimethyl-2,4-dioxoimidazolidin-1-ylmethyl]phenyl}ureido)phenyl]phosphonate. Molecular weight 668.18 (C30H30F5N4O6P); retention time Rt=2.70 min. [E]; MS (ESI): 669.34 (MH+). |