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Structure of 21204-67-1
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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. : | 21204-67-1 |
Formula : | C21H19O2P |
M.W : | 334.35 |
SMILES Code : | O=C([CH-][P+](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)OC |
MDL No. : | N/A |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H301-H315-H319-H335 |
Precautionary Statements: | P261-P264-P270-P271-P280-P301+P310-P302+P352-P304+P340-P305+P351+P338-P312-P330-P362+P364-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 |
---|---|---|
In dichloromethane; at 40℃; for 48h; | To a solution of Example 1A (5.77 g, 0.0192 mol) in anhydrous dichloromethane (30 mL) was added methyl (triphenylphosphoranylidene)-acetate (8.22 g, 0.0246 mol) and the resulting solution heated to 40 C. for two days. The mixture was cooled, concentrated and purified by column chromatography (ethyl acetate/hexane, 4/6) to provide the titled compound (3.42 g). MS (ESI APCI) m/e 355 (M-H)+; 1H NMR (400 MHz, DMSO-d6): delta ppm 5.87 (m, 1H), 4.41-4.78 (m, 4H), 4.31 (d, 1H), 3.74-3.78 (m, 2 H), 3.17 (t, 2H), 3.04 (t, 1H), 2.74-2.80 (d, 1 H), 1.40 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dichloromethane; at 40℃; for 48h; | Example 1B (2S)-4-Methoxycarbonylmethylene-2-(thiazolidine-3-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester To a solution of Example 1A (5.77 g, 0.0192 mol) in anhydrous dichloromethane (30 mL) was added methyl (triphenylphosphoranylidene)-acetate (8.22 g, 0.0246 mol) and the resulting solution heated to 40 C. for two days. The mixture was cooled, concentrated and purified by column chromatography (ethyl acetate/hexane, 4/6) to provide the titled compound (3.42 g). MS (ESI APCI) m/e 355 (M-H)+; 1H NMR (400 MHz, DMSO-d6): delta ppm 5.87 (m, 1H), 4.41-4.78 (m, 4H), 4.31 (d, 1H), 3.74-3.78 (m, 2H), 3.17 (t, 2H), 3.04 (t, 1H), 2.74-2.80 (d, 1H), 1.40 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In toluene; at 90℃; for 1h; | 2.1 g (6.45 mmol, 1.5 eq) of methyl triphenylphosphoranylideneacetate are added to a solution of 900 mg of <strong>[78775-11-8]4-bromo-3-methylbenzaldehyde</strong> in 5 ml of toluene. The reaction mixture is heated at 90°C for 1 hour. The solvent is evaporated off and the residual oil is chromatographed on silica gel (8/2 heptane/ethyl acetate). 610 mg of methyl (E)-3-(4-bromo-3-methylphenyl)acrylate are obtained in oil form. Yield = 55percent over steps a, b and c |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With benzoic acid; In benzene; at 80℃; for 3h; | 500 mg (2.88 mmol) of (2-oxo-propyl)-carbamic acid t-butyl ester obtained in the above step (2) was dissolved in 8 mL of benzene, and then 1.45 g (4.33 mmol) of methyl (triphenyl phosphoranilidene) acetate and 35 mg (0.28 mmol) of benzoic acid was added thereto. The reaction solution was heated to 80C for 3 hours. The solvent was distilled off under reduced pressure, then the residue was purified by column chromatography to give 54 mg (6.64 mmol) of the title compound in a yield of 23% and 301 mg (1.31 mmol) of the trans compound in a yield of 45%.[381] NMR: 1H-NMR(CDCl3) delta 5.77(1H, s), 5.17(1H, brs), 4.16(2H, d, J=6.4Hz),3.69(3H, s), 2.05(3H, s), 1.44(9H, s)[382] Mass(EI) 230(M++.) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; for 16h;Heating / reflux; | Preparation 74: (_E)-3-(4-Benzyloxy-2-fTuorophenyl)acrylic acid methyl ester; <n="47"/>(Triphenyl-lambda*5*-phosphanylidene)acetic acid methyl ester (25.0 g, 74.8 mmol) was added to a solution of <strong>[504414-32-8]4-benzyloxy-2-fluorobenzaldehyde</strong> (9.10 g, 39.5 mmol) in THF (400 inL) and the resulting solution was stirred under reflux conditions for 16 h, before being absorbed onto silica and purified by column chromotogarphy (EtOAc-IH, 1:3) to afford the title compound: RT = 4.15 min; mlz (ES+) = 287.17 [M + H]+. | |
In tetrahydrofuran; for 16h;Reflux; | Methyl (triphenylphosphoranylidene)acetate (25.Og, 74.8mmol) was added to a solution of <strong>[504414-32-8]4-benzyloxy-2-fluorobenzaldehyde</strong> (9.1Og, 39.5mmol) in THF (40OmL) and the resulting solution was stirred under reflux conditions for 16h, before being absorbed onto silica and purified by column chromotogarphy (IH: EtOAc, 3:1) to afford the title compound: RT = 4.15 min; m/z (ES+) = 287.2 [M + H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | In toluene; at 60℃; | EXAMPLE 26; S-C-Methoxypyridin^-yO-N'-CCS-methylquinolin-- yl)methylene)propanehydrazide; [0547] (a) (E)-Methyl 3-(6-methoxypyridin-2-yl)acrylate: To a stirred solution of <strong>[54221-96-4]6-methoxypyridine-2-carboxaldehyde</strong> (0.35 mL, 2.9 mmol) in toluene was added methyl (triphenylphosphoranylidene) acetate (1.95 g, 5.8 mmol) and the reaction was heated at 60 0C overnight. The reaction was diluted with EtOAc and washed with water, brine and dried (Na2SO4). Purification on silica gel using EtOAc-hexane (0 to 30percent) provided 530 mg (94percent) of the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | In toluene;Reflux; | Example 1 5B: 3 -(E)-methyl 3 -(bromo-5-methoxyphenyl)acrylate j00296j Example 15A (0.48 g, 2.232 mmol) was dissolved in toluene (26.6 mL). Methyl (triphenylphosphoranylidine)acetate (0.746 g, 2.232 mmol) was added, and the reaction heated to reflux overnight. The reaction was cooled to ambient temperature andconcentrated in vacuo. The crude material was purified by silica gel column chromatography (gradient from 0 to 100% EtOAc in hexanes) to yield Example 15B (0.580 g, 2.14 mmol, 96% yield). MS (ESI) m/z: 271/273 (M+H). ?HNMR(400 MHz, CHLOROFORM-cl) oe ppm 7.56 (1 H, d, J=16.06 Hz), 7.26 (1 H, s), 7.07 (1 H, s), 6.95 (1 H, s), 6.41 (1 H, d, J=16.06 Hz), 3.82 (3 H, s), 3.81 (3 H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | In acetonitrile; at 20℃; | A mixture of 4-(4-chlorophenyl)benzaldehyde (1.0 g, 4.6 mmol) and methyl 2- (triphenyl-X5-phosphanylidene)acetate (2.0 g, 6.0 mmol) in acetonitrile (12 mL) was stirred atroom temperature overnight. It was purified with ISCO, 24 g column, eluded with 0-30%iPrOAc/heptane to give 1.18 g (94%) of methyl (E)-3-(4?-chloro- [1,1 ?-biphenylj -4-yl)acrylate as white solid. LC-MS: mlz = 273 [M + H] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In toluene; at 100 - 110℃; for 16h;Inert atmosphere; | A solution of methyl 2-(triphenyl-lambda5-phosphanylidene)acetate (3.89 g, 11.62 mmol) and <strong>[22929-52-8]tetrahydrofuran-3-one</strong> (1.00 g, 11.62 mmol) in toluene (10.0 mL) was stirred at 100-110 °C for 16 hrs under nitrogen. On completion, the mixture was concentrated to remove the solvent, the residue was diluted with ethyl acetate (30 mL) and filtered, and the filtrate was concentrated to get the crude product. The crude product was purified by column chromatography (petroleum ether:ethyl acetate = 30:1 to 10:1) to yield the title compound. 1H NMR (400MHz, CDCl3) delta = 5.98 - 5.84 (m, 1 H), 4.72 (s, 2 H), 3.88 (t, J = 6.90 Hz, 2 H), 3.70 (s, 3 H), 2.76 - 2.67 (m, 2 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.6 g | In tetrahydrofuran; for 6h;Inert atmosphere; Reflux; | Examples 8 (0454) [(3R, 4R)-3-Hydroxy-4-methyl-6-(2-hydroxyethyl)-N-MeNle]-1-[(S)-(4- hydroxybutylthio)methyl-Sar]-3-cyclosporin [(3R, 4R)-3-Acetyloxy-4-methyl-(6-methoxycarbonylmethylene)-N-MeNle]-1-cyclosporin (0455) (0456) [0198] To a solution of methoxycarbonylmethylenetriphenylphosphorane (6.20 g, 18.54 mmol) in anhydrous tetrahydrofuran (100 ml) under nitrogen was added [(3R,4R)-3- acetyloxy-4-methyl-6-oxo-N-MeNle]-1-cyclosporin (4.10 g, 3.33 mmol). The mixture was stirred and heated to reflux for six hours. Then saturated ammonium chloride solution (20 ml) was added to quench the reaction. Most of tetrahydrofuran was evaporated under reduced pressure. Ethyl acetate (150 ml) and brine (50 ml) were added and the mixture was separated. The organic layer was dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by chromatography (dichloromethane/methanol) to give 3.60 g of pure [(3R,4R)-3-acetyloxy-4-methyl-(6-methoxycarbonylmethylene)-N-MeNle]-1-cyclosporin [Molecular Formula: C65H113N11O15; Exact Mass: 1287.84; MS (m/z): 1288.61 (M+1)+; HPLC RT: 16.43 min. (C8 reverse phase column: 250 mm; acetonitrile/water (0.05% trifluoroacetic acid); operation temperature: 64 C; detector: 210 nm)]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.9 g | In toluene; at 20℃; for 19h;Inert atmosphere; Reflux; | To a stirred of 6-Oxo-2-aza-spiro[3.3]heptane-2-carboxylic acid tert-butyl ester (2.00 g; 9.47 mmol; 1.0 eq.) in toluene (30 mL), were added methyl (triphenylphosphoranylidene)acetate (3.48 g; 10.41 mmol; 1.1 eq). The resulting suspension was stirred for 3 hours at reflux and left to stir over 16 hours at room temperature. The suspension was filtered and the solid washed with MTBE (2 X 10 mL). The filtrate was concentratted to dryness and purified by flash chromatography (silica gel, EtOAc-heptane 10/90) to afford (1.9 g) tert-butyl 6-(2-methoxy-2-oxoethylidene)-2-azaspiro[3.3]heptane-2-carboxylateas a colourless oil.MS(ES+) m/z 168(M-Boc+H+). |