Structure of 162427-79-4
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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. : | 162427-79-4 |
Formula : | C8H9FO |
M.W : | 140.15 |
SMILES Code : | C[C@@H](O)C1=CC=CC=C1F |
MDL No. : | MFCD03092991 |
InChI Key : | SXFYVXSOEBCFLV-ZCFIWIBFSA-N |
Pubchem ID : | 2779054 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 37.33 |
TPSA ? Topological Polar Surface Area: Calculated from |
20.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.97 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.54 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.97 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.3 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.25 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.01 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.06 |
Solubility | 1.23 mg/ml ; 0.00877 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.57 |
Solubility | 3.74 mg/ml ; 0.0267 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.51 |
Solubility | 0.433 mg/ml ; 0.00309 mol/l |
Class? Solubility class: Log S scale |
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) |
Yes |
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 |
-6.06 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
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 |
2.0 |
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 |
0.0 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) |
1.44 |
* 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 |
---|---|---|
100% | With RuBr2[(S,S)-2,4-bis(diphenylphosphino)pentane](2-picolylamine); potassium tert-butylate; hydrogen; In ethanol; at 40℃; under 7600.51 Torr; for 19h;Inert atmosphere; Autoclave; | General procedure: In an autoclave, 1.32 mg of RuBr2[(S,S)-xylskewphos] (3,5-Me2pica) (1.29×10-3 mmol, S/C=10000) and 5.79 mg of potassium tert-butoxide (5.16×10-2 mmol) are placed, and replaced with argon gas. Under argon gas flow, 1.5 mL of acetophenone (12.9 mmol) and 2.9 mL of ethanol was added while measuring by a syringe, pressurized with hydrogen to 10 atm, stirred at 40 C. for 19 hours, then the reduction of the hydrogen pressure was confirmed and phenylethanol was obtained at 100% yield. The optical purity was 88.0% ee as measured by GC (CP-Chirasil-DEX CB (0.25 mml. D×25 m, DF=0.25 mum, from VARIAN), constant at 110 C., pressure: 102.0 kPa, column flow: 1.18 mL/min, vaporizing chamber temperature: 250 C., detector temperature: 275 C., the retention time of each enantiomer was: (R): 11.7 min, (S): 12.4 min), and (S) isomer has predominantly been generated.The reaction was carried out in similar way as Working Example 1 except that the complex was changed to RuBr2 [(S,S)-xylskewphos](pica), and the reaction solvent and substrate were changed as indicated in the Table below. The results are summarized in the Table below, which also describes the results from Comparative Example 1. Analysis conditions indicated in the Table is the same as the Table provided from Working Examples ito 6. From the results, it is clear that RuBr2[(S,S)-xylskewphos] (3,5-Me2pica) has a better enantioselectivity as compared to RuBr2[(S,S)-xyl- skewphos] (pica) complex. |
With (S,S)-DPENDS; C36H24Cl2O18P2RuS6(6-)*6Na(1+); hydrogen; potassium hydroxide; In water; at 30℃; under 37503.8 Torr; for 3h;Autoclave; | General procedure: To a 60 mL stainless autoclave with a glass liner and magnetic stirrer were added PEG-400, H2O, RuCl2(TPPTS)2, (S,S)-DPENDS, KOH, and reactant. Hydrogen was introduced to the desired pressure after the reaction mixture had been purged with H2 five times. The products were extracted by n-hexane and analyzed by GC-960 with a FID detector and beta-DEX120 capillary column (30 m × 0.25 mm, 0.25 mum film) at 115 C. The enantiomeric excess (ee value) was calculated from the equation: ee (%) = 100 × (R - S)/(R + S). | |
With dodecacarbonyl-triangulo-triruthenium; (S,S)-N-{1,2-diphenyl-2-[(pyridin-2-ylmethyl)amino]ethyl}-4-methylbenzenesulfonamide; In isopropyl alcohol; at 80℃; for 48h;Inert atmosphere; Schlenk technique; | General procedure: A mixture of catalyst (2 mol%) and Ru3 (CO)12 (0.67 mol%) in IPA (10 cm3) was stirred at 80 C under an inert atmosphere in a schlenk tube for 30 min. To this solution, ketone (1 mmol) was added and the resulting mixture was stirred at 80 Cfor 48 h. The reaction mixture was filtered through a short column of silica using (EtOAc:hexane 1:1), a small amount of the filtrate was dilluted in EtOAc and then injected on the GC to determine the conversion and enantiomeric excess. |
With formic acid; (S,S)-RuCl(eta6-CH3C6H4CH2CH2CH2CH2NHCH(C6H5)CH(C6H5)NSO2Ts); C32H35ClN2O2RuS; triethylamine; at 60℃; for 5h;Schlenk technique;Catalytic behavior; | General procedure: As Examples 20 to 35, hydrogen transfer reactions to ketones shown in Tables 1, 2, and 3 below were conducted by the same operation as in Examples 16 and 18. In these reactions, the catalyst ratios (S/C) were as shown in the tables, the reaction temperature was 60 C., and a formic acid-triethylamine (5:2) azeotrope was used as a hydrogen source in such an amount that the concentration of the substrate was 2 mol/L. The conversions and the optical purities were determined by analyzing the reaction liquids by GC after predetermined periods.; In addition, as Comparative Examples, results of reactions in which RuCl ((S,S)-Tsdpen) (mesitylene) was used in the same manner are also shown in each table. Note that, in these tables, conv. represents the conversion of the ketone substrate, selec. represents the selectivity for the target product, % ee represents the optical purity, and S/C represents a value represented by the number of moles of the ketone substrate/the number of moles of the catalyst. | |
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; C26H29N4O3S(1+)*Cl(1-); sodium formate; In water; at 20℃; for 5h;Catalytic behavior; | General procedure: To a solution of ligand 5d (2.1 mg, 0.004 mmol) in water (1 mL) was added [Cp*RhCl2]2 (1.2 mg, 0.002 mmol), HCO2Na (41 mg, 3.0 mmol), and ketone (2.0 mmol). The reaction mixture was stirred at room temperature for the time as indicated in Tables 1 and 2 . The reaction mixture was extracted by ethyl ether. The conversion was determined by 1H NMR analysis of the crude product. After concentration, the crude product was purified by chromatography on silica gel to give the pure product. | |
With dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; C26H29N4O3S(1+)*Cl(1-); sodium formate; In water; at 20℃; for 5h;Green chemistry; | General procedure: To a solution of ligand 5d (2.1 mg, 0.004 mmol) in water (1 mL) was added [Cp*RhCl2]2 (1.2 mg, 0.002 mmol), HCO2Na (41 mg, 3.0 mmol), and ketone (2.0 mmol). The reaction mixture was stirred at room temperature for the time as indicated in Tables 1 and 2. The reaction mixture was extracted by ethyl ether. The conversion was determined by 1H NMR analysis of the crude product. After concentration, the crude product was purified by chromatography on silica gel to give the pure product. | |
General procedure: In a schlenk tube, BH3·SMe2(0.55 mmol, 275 L) was added inthe solution of IL 5 (28 mg, 10 mol%) dissolved in THF (1 mL), undernitrogen atmosphere. The homogenous mixture was stirred andheated at 70C for 30 min. Later, a solution of ketone (0.5 mmolin THF (0.5 mL)) was added within 30 min. After the addition wascompleted, the solvent was evaporated under vacuum. An aqueoussolution of 1M HCl (5 mL) was added and the product was extractedwith DCM. The solvent was dried on anhydrous sodium sulfateand evaporated under reduced pressure. Crude residue was furtherpurified by column chromatography on silica gel using hexane-ethyl acetate as eluent. Enantiomeric excesses of all alcohols weredetermined by HPLC analysis using Chiralcel OD-H/AD-H chiralcolumn, isopropanol-n-hexane as mobile phase and HPLC condi-tions are given in SI. | ||
With (2R)-2-[benzyl([6-({benzyl[(1R)-2-[(diphenylphosphanyl)oxy]-1-phenylethyl]amino}methyl)pyridin-2-yl]methyl})amino]-2-phenylethyl diphenylphosphinite bis(dichloro-eta6-p-cymeneruthenium(II)); isopropyl alcohol; potassium hydroxide; at 82℃; for 0.5h;Inert atmosphere; Schlenk technique;Catalytic behavior; | General procedure: Typical procedure for the catalytic hydrogen-transfer reaction: a solution of the Ru(II)-complexes 17-24 (0.005 mmol), KOH (0.025mmol) and the corresponding ketone (0.5 mmol) in degassed 2-propanol (5 mL) was refluxed until the reaction was completed. Periodically samples taken from the reaction medium were passed through acetone silica gel column and conversion rates were observed in gas chromatography, which were calculated based on unreacted ketone. | |
With [(1S,2S)-N-(p-toluensulfonyl)-1,2-diphenylethanediamine](p-cymene)ruthenium (I); sodium formate; In methanol; water; at 50℃; for 12h;Green chemistry; | 0.5 mmol of 1-(2-fluorophenyl)ethanol was added to the test tube, 1.5 mmol of dipropylene glycol dimethyl ether was added to the oxygen balloon, and the reaction was completed at 120 C for 12 hours until the reaction was completed, and sodium formate was added to the reaction system, 2.5 mmol. Then add 0.0025 mmol of catalyst B, add 4 mL of methanol:water (3:1), replace with nitrogen three times, react at 50 C for 12 h, wash with water after the reaction, extract the aqueous phase with ethyl acetate three times, and concentrate the organic phase to dry Column chromatography (petroleum ether: ethyl acetate = 10:1) gave (S)-1-(2-fluorophenyl)ethanol (61.6 mg), yield 88%, ee value 86%. HPLC separation conditions: chiral column OD-H column, mobile phase: n-hexane / isopropanol = 98: 2 (volume ratio), flow rate: 1.0 ml / min, wavelength: 254 nm, temperature, 25 C, t1 = 11.82min, t2=12.72min; | |
With glucose dehydrogenase; D-glucose; NAD; acetophenone reductase from Geotrichum candidum NBRC 4597 (Trp288Ala mutant); In aq. buffer; at 30℃; for 14h;pH 7.2;Enzymatic reaction;Kinetics; | General procedure: Reductions were performed in 50 mL of 100 mM HEPES-NaOH buffer (pH 7.2) consisting of1.4 mM NAD+, 0.23-0.39 mmol of 2a-13a, cofactor regeneration reagent written in Table S1, and purified GcAPRD with the amount written in Table S1. Reactions were done for 14 h at 30C with a rotational speed of 130 rpm. The product was extracted with diethyl ether, dried over MgSO4, and evaporated under reduced pressure. Silica gel column chromatography (hexane:ethyl acetate 4:1) were performed to give the corresponding chiral alcohols 2b-13b. |
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