Structure of 1034287-04-1
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CAS No. : | 1034287-04-1 |
Formula : | C14H17BO2 |
M.W : | 228.09 |
SMILES Code : | CC1(C)C(C)(C)OB(C2=CC=C(C#C)C=C2)O1 |
MDL No. : | MFCD16294504 |
InChI Key : | LOVNTFMVZVIASV-UHFFFAOYSA-N |
Pubchem ID : | 57415690 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 17 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.43 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 70.85 |
TPSA ? Topological Polar Surface Area: Calculated from |
18.46 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 |
3.15 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.05 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.19 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.53 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.98 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.43 |
Solubility | 0.084 mg/ml ; 0.000368 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.21 |
Solubility | 0.141 mg/ml ; 0.00062 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.09 |
Solubility | 0.0187 mg/ml ; 0.000082 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
Yes |
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 |
-5.45 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 |
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 |
2.0 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) |
3.04 |
* 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 |
---|---|---|
60% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; diisopropylamine; In ethanol; at 25℃; for 3h;Inert atmosphere; | General procedure: PdCl2(PPh3)2 (3.5 mg, 5.0 mumol, 1 mol %) and CuI (4.8 mg, 25 mumol) were mixed with EtOH (2 mL) in a glass vial equipped with a screw cap. Diisopropylamine (140 muL, 1.0 mmol) was added and the vial was flushed with argon. (E)-N-(2-Iodovinyl)phthalimide 1 (150 mg, 0.50 mmol) and the appropriate acetylene (0.55 mmol 1.1 equiv) were added and the mixture was stirred for 3 h. After the reaction was completed (GC-MS analysis) the volatiles were evaporated under vacuum and the crude product was chromatographed on silica gel (eluent: EtOAc in n-hexane 0-50%) to afford the analytically pure products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69%Chromat. | With [{Ir(mu-Cl)(CO)2}2]; N-ethyl-N,N-diisopropylamine; In toluene; at 80℃; for 24h;Schlenk technique; Inert atmosphere; | General procedure: A glass Schlenk reactor (10 mL) equipped with a magnetic stirbar was evacuated and flushed with argon. The calculated amountof [{Ir(l-Cl)(CO)2}2] complex (0.005 or 0.0025 mmol) was placed inthe reactor under the flow of argon, then 3 mL of solvent and amine (1.8 mmol) were added. The obtained mixture was stirred forabout 10 min. In the next step, the terminal alkyne (1 mmol) andR3SiI (1.6 mmol) were added, and the reaction was conducted atthe given temperature. The mixture was analyzed by GC and GC/MS at the beginning and after 24 or 48 h. The conversions andyields were calculated using the internal standard calculationmethod. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With [{Ir(mu-Cl)(CO)2}2]; N-ethyl-N,N-diisopropylamine; In toluene; at 80℃; for 24h;Schlenk technique; Inert atmosphere; | General procedure: Synthesis of 4-(trimethylsilylethynyl)biphenyl(3) A reactor with a capacity of 40 mL, equippedwith a magnetic stirrer was charged, under argon atmosphere, with 0.0085 g(0.015 mmol) of [{Ir(mu-Cl)(CO)2}2],and then with 20 mL of anhydrous and deoxidized toluene and 0.7g (5.4 mmol) ofNEt(i-Pr)2.The whole mixture was stirred until the starting iridium(I) complex wasdissolved, and then 0.535g (3mmol) of 4-ethynylbiphenyl and0.96 g (4.8 mmol) of ISiMe3were added to the resulting mixture. The reaction was carried out at a temperature of 80oC untilcomplete conversion of 4-ethynylbiphenyl. After the reaction was completed, in order to remove the catalyst from the reaction mixture thesolvent and unreacted substrates were evaporated at a reduced pressure. The silylation product was extracted bymeans of pentane using a cannula system. The solvent was initially evaporated from the extract, and then the raw product waspurified on a SiO2-packedcolumn (modified with a 15% hexane solution of Et3N), using hexaneas eluent. The product was 0.721 g of4-(trimethylsilylethynyl)biphenyl, obtained with a yield of 96%. Synthesisof 2-(4-trimethylsilylethynylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborate(9)Following theprocedure used for preparation of compound 3, a reaction was carried outbetween:- 0.684 g (3mmol) of 2-(4-ethynylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborate- 0.96g (4.8 mmol) of ISiMe3in the presence of:- 0.017g (0.03 mmol) of the complex [{Ir(mu-Cl)(CO)2}2]- 0.70g (5.4 mmol) of NEt(i-Pr)2 The product was 0.865 g of 2-(4-trimethylsilylethynylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxoborate,obtained with a yield of 96%.Analysis calculatedfor C17H25BO2Si C 68.00; H 8.39; found C68.15; H 8.42; 1H NMR (300 MHz, CDCl3,300 K) d(ppm) = 7.73 (d, 3J=8.2 Hz, 2H, -C6H4-);7.46 (d, 3J=8.2 Hz, 2H, -C6H4-);1.31 (s, 12H,-Me2C-CMe2-); 0.23 (s, 9H, -SiMe3);13C NMR (75.45 MHz, C6D6,300 K) d(ppm) = 134.64; 131.48; 131.31; 125.93;105.35 (-C?C-SiMe3); 95.76 (-C?C-SiMe3);84.17; 25.09; 0.16 (-SiMe3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | With copper(I) thiophene-2-carboxylate; bis(pinacol)diborane; In chloroform-d1; at 60℃; for 18h; | General procedure: To a 3mL vial was added CuTc (1.9mg, 0.01mmol, 10mol%), B2pin2 (2.5mg, 0.01mmol, 10mol%), 1a (47.4mg, 0.15mmol, 1.5equiv), substrate (0.1mmol, 1equiv), and 0.5mL of CDCl3. The reaction mixture was stirred for 18h at 60C. The products were purified by silica gel column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 40℃; for 12h;Schlenk technique; Inert atmosphere; | Compounds 26 (228 mg, 1.0 mmol)and 25 (385 mg, 1.6 mmol) were dissolved in dry THF-EtN(i-Pr)2, 15:1 (16 ml) mixture. After 10 min of bubblingwith Ar, PdCl2(PPh3)2 (40 mg, 0.035 mmol), CuI (20 mg,0.110 mmol) were added, and the reaction mixture was stirredat 40C for 12 h. The cooled reaction mixture was dilutedwith H2O (50 ml) and extracted with CH2Cl2 (2×30 ml).The combined organic extracts were dried (Na2SO4), thesolvents were evaporated in vacuo, and the crude productwas purified by column chromatography (SiO2, hexane-CH2Cl2, 2:1). Yield 260 mg (77%), pale-yellow solid, mp223-226C. 1H NMR spectrum, delta, ppm (J, Hz): 1.34 (12H,s, 4CH3); 3.90 (3H, s, OCH3); 6.10 (1H, d, J = 4.0, H Th);6.95 (1H, d, J = 4.0, H Th); 7.46 (2H, d, J = 8.4, H Ar);7.75 (2H, d, J = 8.4, H Ar). 13C NMR spectrum, delta, ppm:25.1; 60.4; 83.7; 85.0; 91.4; 104.3; 109.6; 126.1; 130.5;131.2; 134.8; 167.5. Mass spectrum, m/z (Irel, %): 340 [M]+(100), 325 (100), 225 (20), 197 (13). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With 1,1'-bis-(diphenylphosphino)ferrocene; (hydridotris(1-pyrazolyl)borato)(1,5-cyclooctadiene)rhodium(I); In acetonitrile; at 110℃; for 12h;Inert atmosphere; Sealed tube; Glovebox; | In an anhydrous, argon-filled glovebox, a 4 mL vial was charged with TpRh(COD) (6.3 mg, 15 mol, 7.5 mol%), dppf (8.3 mg, 15 mol, 7.5 mol%), and MeCN (1 .0 mL, c = 0.2 M). 2- (4-Ethynylphenyl)-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (45.6 mg, 0.200 mmol, 1 .00 equiv) and acetone cyanohydrin (20.4 mg, 23.5 mu, 0.240 mmol, 1.20 equiv) were then added to the reaction mixture. The vial was sealed with a Teflon cap and moved from the glovebox to a preheated metal heating block (1 10 C). The reaction mixture was then stirred at 1 10 C for 12 hours. After cooling to 23 C, the resulting mixture was filtered - - through a short plug of silica gel, eluting with EtOAc. The filtrate was collected and concentrated in vacuo. The resulting residue was purified by flash column chromatography on silica gel, eluting with EtOAc/hexane 1 :10 (v/v) to afford 34.7 mg (68%) of the title compound as pale yellow liquid.Rf = 0.35 (EtOAc/hexanes 1 :10 (v/v)).NMR Spectroscopy:1H NMR (500 MHz, CDCI3, 23 C, delta): 7.85 (d, J = 8.0 Hz, 2H), 7.46 (d, J = 8.0 Hz, 2H), 7.43 (d, J = 16.5 Hz, 1 H), 5.96 (d, J = 16.5 Hz, 1 H), 1 .37 (s, 12H).13C NMR (125 MHz, CDCI3, 23 C, delta): 150.5, 135.8, 135.4, 126.5, 1 18.1 , 97.2, 84.2, 24.9. HRMS-FIA (m/z) calc'd for C15H18N02[M+Na]+, 278.1323; found: 278.1324. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With copper(l) iodide; N-cyclohexyl-cyclohexanamine; In water; at 45℃; for 3h;Inert atmosphere; | General procedure: CuI (10mol%), 1 (1 equiv, 0.5mmol), and 2 (2 equiv, 1.0mmol) were sequentially added under air to a dram vial equipped with a stir bar. Amine (1.5 equiv, 0.75mmol), and distilled water (1.0mL) were added by syringe, and the resulting mixture was vigorously stirred under nitrogen atmosphere [charged by general N2 (99.95%) gas flow] for 20hat the temperature, as shown in the tables. After this time, the contents of the flask were extracted with ethyl acetate and then concentrated by rotary evaporation. The residue was purified by flash chromatography, eluting with hexane/EtOAc to afford the product 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With platinum(0)-1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex; In toluene; at 100℃; for 24h;Green chemistry; | General procedure: A silane and an appropriate alkyne were placed in a 25cm3 round bottom flask equipped with a stirrer and a glass stopper. The reagents were dissolved in toluene or THF and Karstedt?s catalyst was added. Subsequently, the reaction mixture was heated to 60C or 100C, depending on the reaction. Samples of the reaction mixture were collected in intervals, and the conversion of SiH was determined by 1H NMR and GC-MS. Then the reactions were repeated in determined reaction time, and the resulting mixtures were isolated by the evaporation of the solvent under vacuum. Products were characterized by 1H, 13C, 29Si NMR, GC-MS analysis. The platinum residue was removed by filtration of petroleum ether solution through silica gel. After evaporation of solvents, the products were dried for 6h under vacuum. Isolated products were characterized by 1H, 13C, 29Si NMR, GC-MS. For new compounds, elemental analysis was performed as well. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With platinum(0)-1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex; In toluene; at 100℃; for 24h;Green chemistry; | General procedure: A silane and an appropriate alkyne were placed in a 25cm3 round bottom flask equipped with a stirrer and a glass stopper. The reagents were dissolved in toluene or THF and Karstedt?s catalyst was added. Subsequently, the reaction mixture was heated to 60C or 100C, depending on the reaction. Samples of the reaction mixture were collected in intervals, and the conversion of SiH was determined by 1H NMR and GC-MS. Then the reactions were repeated in determined reaction time, and the resulting mixtures were isolated by the evaporation of the solvent under vacuum. Products were characterized by 1H, 13C, 29Si NMR, GC-MS analysis. The platinum residue was removed by filtration of petroleum ether solution through silica gel. After evaporation of solvents, the products were dried for 6h under vacuum. Isolated products were characterized by 1H, 13C, 29Si NMR, GC-MS. For new compounds, elemental analysis was performed as well. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With platinum(0)-1,3-divinyl-1,1,3,3-tetramethyldisiloxane complex; In toluene; at 100℃; for 24h;Green chemistry; | General procedure: A silane and an appropriate alkyne were placed in a 25cm3 round bottom flask equipped with a stirrer and a glass stopper. The reagents were dissolved in toluene or THF and Karstedt?s catalyst was added. Subsequently, the reaction mixture was heated to 60C or 100C, depending on the reaction. Samples of the reaction mixture were collected in intervals, and the conversion of SiH was determined by 1H NMR and GC-MS. Then the reactions were repeated in determined reaction time, and the resulting mixtures were isolated by the evaporation of the solvent under vacuum. Products were characterized by 1H, 13C, 29Si NMR, GC-MS analysis. The platinum residue was removed by filtration of petroleum ether solution through silica gel. After evaporation of solvents, the products were dried for 6h under vacuum. Isolated products were characterized by 1H, 13C, 29Si NMR, GC-MS. For new compounds, elemental analysis was performed as well. |