Structure of 2605-68-7
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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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Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 2605-68-7 |
Formula : | C22H21O2P |
M.W : | 348.38 |
SMILES Code : | COC(=O)C(C)=P(C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 |
MDL No. : | MFCD08062441 |
InChI Key : | WCXPAYJKBTVUBC-UHFFFAOYSA-N |
Pubchem ID : | 10569721 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 25 |
Num. arom. heavy atoms | 18 |
Fraction Csp3 | 0.09 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 107.97 |
TPSA ? Topological Polar Surface Area: Calculated from |
36.11 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.96 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.35 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.73 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
5.42 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.49 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.7 |
Solubility | 0.00699 mg/ml ; 0.0000201 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-4.42 |
Solubility | 0.0133 mg/ml ; 0.0000381 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-8.02 |
Solubility | 0.00000337 mg/ml ; 0.0000000097 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.61 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
3.97 |
* 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 |
---|---|---|
97% | A mixture of methyl-2-bromopropionate (S7) (2.00 mL, 17.9 mmol, 1.10 eq) and triphenylphosphine (4.27 g,16.3 mmol, 1.00 eq) in water (18.0 mL) was stirred at 70 C for 2.5 h. Both the aqueousand the organic layer still contained PPh3. The temperature was raised to 80 C and themixture was stirred for further 2 h. According to TLC, there was still a considerableamount of PPh3. Therefore, the mixture was stirred at 75 C overnight. After totally 23 hthe mixture was allowed to cool to rt. Afterwards aqueous NaOH (38 mL 1 M, 2.3 eq) wasadded, which led to the immediate precipitation of a yellow solid. The suspension wasstirred for 5 min, then CH2Cl2 (50 mL) was added and the layers were separated. Theaqueous phase was extracted with CH2Cl2 (2×50 mL), washed with brine, dried overMgSO4 and concentrated under reduced pressure. The crude was obtained as a yellow oil,which turned into a solid upon addition of pentane. The solid was washed with hexane(3×20 mL) and dried in vacuo to afford phosphonium ylide 17 (5.48 g, 97%) as a slightlyyellow powder. | |
91% | With potassium iodide; In water; toluene; at 70℃; for 20h; | After dissolving 5 g (19.06 mmol) of triphenylphosphine in 15 ml of toluene, an aqueous solution of 0.32 g (1.90 mmol) of potassium iodide in 15 ml of distilled water and 3.2 ml (28.6 mmol) of methyl 2-bromopropionate were added thereto. And the mixture was stirred at 70 C for 20 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, basified (pH 9) with 10 N aqueous sodium hydroxide solution, and extracted with dichloromethane. The obtained organic layer was dried over anhydrous sodium sulfate, filtered under reduced pressure, and distilled under reduced pressure. The obtained solid was washed with hexane and then filtered under reduced pressure and dried under reduced pressure to give 6.0 g (yield: 91%) of the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In dichloromethane; water; at 20℃; for 0.25h;Inert atmosphere; | Sodium hydroxideaq. (2 M, 85 mL, 170mmol) was added to a solution ofcarbomethoxy methyl triphenylphosphonium bromide (5.15 g,12.0mmol) and CH2Cl2 (20 mL) at room temperature. Afterstirring for 15min at room temperature, the solution wasextracted with CHCl3 (2 15 mL), washed with brine (15 mL),dried over Na2SO4 and concentrated. The resulting ylide wasused without further purification. A solution of the ylide and CH2Cl2 (30 mL) was added to asolution of lactol 36 (1.00 g, 5.98mmol) and CH2Cl2 (30 mL) atroom temperature. After maintaining for 19 h at room temperature,diisopropylethylamine (5.2 mL, 30mmol) and BOMCl(3.3 mL, 24mmol) were added to the yellow solution at roomtemperature. The solution was maintained for 2 d at roomtemperature, quenched with H2O (40 mL) and extracted withCHCl3 (3 30 mL). The combined organic extracts werewashed with brine (30 mL), dried over Na2SO4 and concentrated.The residue was purified by silica gel column chromatography(EtOAc/hexane 1:24 to 1:7) to give 2.27 g of a mixtureof the unsaturated methylester 37 and benzyl alcohol, whichwas used in the next step without further purification. Foran analytical sample, the mixture was purified by HPLC(PEGASIL Silica 1205250 20 mm, UV 254 nm, EtOAc/hexane 1:3, 10mL/min, TR = 12min) to afford the pureunsaturated methylester 37 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | In dichloromethane; at 47℃; for 3h; | To a solution of the phosphonium ylide17 (62.1 g, 178 mmol, 1.00 eq) in CH2Cl2 (230 mL) was added acrolein (18) (11.9 mL,178 mmol, 1.00 eq) dropwise at rt. The addition was ceased from time to time due toexcessive boiling of the mixture. After the addition, the yellow solution was heated (47 Coil bath) to maintain a gentle reflux. After 3 h, the mixture was allowed to cool to rt andstored overnight. Then it was concentrated under reduced pressure (Vigreux, short pathdistillation, “Hausvakuum”, 55 C oil bath), which took several hours. The concentrate wasthen cooled to 0 C, pentane was added, the resulting suspension was filtered and the filtercake was washed with pentane. The combined filtrates were concentrated (Vigreux, shortpath distillation, 50 C oil bath) and the crude was purified by distillation (75-77 oil bath, 20 mbar, bp = 59-60 C) to afford 19 as a colourless liquid (70%).1H-NMR (CDCl3, 400.1 MHz): δ = 7.17 (mc, 1H), 6.66 (ddd, J = 10.1 Hz, J = 11.3 Hz, J = 16.8 Hz, 1H), 5.56 (mc, 1H), 5.45 (mc, 1H), 3.77 (s, 3H), 1.96 (mc, 3H). |