Structure of 214360-70-0
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CAS No. : | 214360-70-0 |
Formula : | C10H15BO2S |
M.W : | 210.10 |
SMILES Code : | CC1(C)C(C)(C)OB(C2=CSC=C2)O1 |
MDL No. : | MFCD05663893 |
InChI Key : | HQXQOBAEDQBINI-UHFFFAOYSA-N |
Pubchem ID : | 2760597 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302+H312+H332-H315-H319-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.6 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 60.8 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.7 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 |
2.59 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.05 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.22 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.5 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.67 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.97 |
Solubility | 0.224 mg/ml ; 0.00107 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.22 |
Solubility | 0.127 mg/ml ; 0.000603 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.27 |
Solubility | 0.112 mg/ml ; 0.000535 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) |
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 |
-5.74 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 |
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) |
2.98 |
* 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 |
---|---|---|
[00379] In a reaction tube under nitrogen, a mixture of PdCl2(dppf)CH2Cl2 (21 mg; 0.026 mmol) and triethylamine (0.34 ml; 2.44 mmol) in dioxane (2.5 ml; dried over 4 A sieves) was sealed and stirred at 80 C. overnight (18 h). After cooling to room temperature, HB(pin) (0.19 ml; 1.31 mmol) was added followed by 3-bromothiophene (137 mg; 0.840 mmol) in dioxane (2.5 ml; dried over 4 A sieves) and the reaction mixture was stirred at 80 C. GC analysis after 18 hours showed the desired borate compound at 5.1 minutes. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; at 60℃; | The starting material, 2-(4-(thiophen-3-yl)phenyl)ethanol, was synthesized asfollows: In a sealed vessel was combined 2-(4-bromophenyl)ethanol (70 jxL), 4,4,5,5-tetramethyl-2-(thiophen-3-yl)-l,3,2-dioxaborolane (126 mg), K2CO3 (207 mg), catalyticPd(PPh3)4, 4.5 mL THF, and 0.5 mL H2O. The vessel was heated in an oil bath at 60 Covernight. The reaction mixture was diluted with water and DCM. The organic layerwas concentrated to yield 2-(4-(thiophen-3-yl)phenyl)ethanol (80 mg) as a solid whiteproduct. 80 mg tert-butyl (S)-2-(4-(4-(thiophen-3-yl)phenethyloxy)phenylcarbamoyl)-l-hydroxypropan-2-ylcarbamate was synthesized following the general procedureemploying 2-(4-(thiophen-3-yl)phenyl)ethanol (200 mg), 7V-(Boc)-a-methylserine (175mg), HATU (375 mg), and DIPEA (430 uL). MS (ESI, M+Na+) = 519. 2.6 mg of thephosphate was then synthesized from the carbamate (40 mg) as a solid white solid. MS(ESI, M+H+) = 477; *H NMR (400 MHz, DMSO-d6) 5 9.96 (br s, 1H), 7.81 (m, 1H),7.65 (m, 3H), 7.5 (m, 3H), 7.3 (m, 2H), 6.9 (m, 2H), 4.28 (m, 1H), 4.17 (m, 2H), 4.06(m, 1H), 3.04 (t, 2H), 1.48 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With potassium fluoride;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In methanol; toluene; at 120℃; for 0.25h; | In a microwave tube, N-(5-iodo-4-methyl-l,3-thiazol-2-yl)acetamide, Intermediate 1 (564.2 mg; 2 mmol; 1 eq) and Pd(dppi)Cl2 (73.2 mg; 0.10 mmol; 0.05 eq) are suspended in Toluene (7ml). A solution of potassium fluoride (464.8 mg; 8 mmol; 4 eq) in MeOH (7ml) is added. 3- (4,4,5,5-Tetramethyl-l,3,2-dioxaborolan-2-yl)thiophene (630.3 mg; 3 mmol; 1.50 eq) is finally added as a solid. The resulting solution is flushed with argon, the tube is closed and heated under microwave action at 1200C for 15 minutes. The reaction mixture is filtered over Celite and the solvents are evaporated. The resulting crude product is dissolved in EtOAc, washed with water and brine and dried over MgSO4. It is then purified by preparative HPLC, affording the title compound as white-off solid (316.7 mg; 66% yield). 1H NMR (DMSO-d6, 300 MHz) ? 2.12 (s, 3H), 2.35 (s, 3H), 7.28 (dd, J = 1.5, 4.9 Hz, IH), 7.58 (dd, J = 1.5, 3.0 Hz, IH), 7.67 (dd, J = 3.0, 4.9 Hz, IH), 12.09 (s, IH). M (ESI): 237.03; M+(ESI): 239.03. HPLC (method A), Rt: 2.92 min (purity: 99.6%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; for 67h;Inert atmosphere; Reflux; | Example 1 : 3-[2.4-dinitro-6-(trifluoromethyl)phenvnthiophene; A solution of 2-chloro-3,5-dinitrobenzotrifluoride (214mg, 0.79mmol) and 3- (4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)thiophene (178mg, 0.85mmol) in toluene (3mL) was treated with 2M aqueous sodium carbonate (0.445mL, 0.89mmol). The mixture was flushed with nitrogen and tetrakis(triphenylphosphine)palladium(0) (44mg, 0.04mmol) was added. The mixture was then refluxed under nitrogen for 67 hours. The reaction was allowed to cool and saturated aqueous sodium carbonate (8ml_) was added. The mixture was extracted with dichloromethane (3 x 3OmL) and the combined organic extract was dried over MgSO4 before being evaporated to dryness. The crude product was chromatographed over silica gel. Elution with ethyl acetate/hexanes (1 :9) gave the title compound as a pale yellow solid (96mg, 38%), m.p. 104-50C. 1HNMR (300 MHz, CDCI3): 8.81 , 8.73 (ABq, 2H, J=2.2), 7.46 (dd, 1H, J=5.0, 3.0), 7.35 (br s, 1 H), 7.09 (d, 1 H, J=5.0). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 14h; | General procedure: To a solution of 3-anisyl pinacol borane (50mg, 0.21mmol) in DMF (1mL) was added N-bromosuccinimide (82mg, 0.46mmol). After stirring at room temperature for 14h, resultant solution was treated with 10% Na2S2O3 aq (10 ml) and was extracted with Et2O (10ml×3). The combined organic phase was washed with H2O (10ml×2) and brine (10ml×1) and dried over MgSO4. After removal of solvent under reduced pressure, the residue was chromatographed on silica gel with Hexane to afford 2-bromo-5-methoxyphenyl pinacol borate (57.3mg, 87% yield) as colorless oil |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
38% | With sodium carbonate;bis-triphenylphosphine-palladium(II) chloride; In water; N,N-dimethyl-formamide; at 120℃; for 3h; | Example 31N-((l,2-dihydro-6-methyl-2-oxo-4-propylpyridin-3-yl)methyl)-l-isopropyl-6-(thiophen-3-yl)-lH- indazole-4-carboxamideTo a stirred solution of 6-bromo-N-((l,2-dihydro-6-methyl-2-oxo-4-propylpyridin-3-yl)methyl)-l- isopropyl-lH-indazole-4-carboxamide (0.2 g, 0.44 mmol) in DMF (10 mL) was added 4,4,5,5- tetramethyl-2-(thiophen-3-yl)-l,3,2-dioxaborolane (0.113 g, 0.53 mmol) followed by PdCl2(PPh3)2 (0.06 g, 0.08 mmol) and the reaction mixture was stirred for 5 min. Sodium carbonate (0.119 g, 0.940 mmol) dissolved in water (2 mL) was added and the contents were stirred at 120 C for 3 h. The reaction mixture was diluted with NaHCC>3 solution and extracted with ethyl acetate (3x20 mL). The combined organic layers were washed with brine solution (20 mL), dried over anhydrous Na2S04 , filtered, and concentrated in vacuo to afford the crude product. The crude product was purified by silica gel chromatography (eluent: 4% MeOHYEtOAc) to afford the title compound as an off white solid (75 mg, 38 %) . .H NM (DMSO-d6; 400 MHz): delta 0.883 (t, J = 7.2 Hz, 3H), 1.491-1.550 (m, 8H), 2.13 (s, 3H), 2.501 (s, 2H), 4.419 (d, J = 3.6 Hz, 2H), 5.130 (t, J = 6.4 Etazeta,IotaEta), 5.912 (s, 1H), 7.691 (s, 1H), 7.766 (d, J = 4.4 Hz, 1H), 7.930 (s, 1H), 8.041 (s, 1H), 8.171 (s, 1H), 8.353 (s, 1H), 8.563 (s, 1H), 1 1.530 (s, 1H). LCMS (ES+) m/z: 449.09. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; lithium hydroxide; In 1,4-dioxane; water; at 80℃; for 0.5h;Inert atmosphere; | General procedure: To a solution of 2-chloroheteroaryl compound 1 (0.50 mmol) in 1,4-dioxane (4.0 mL) were added pinacol boronate 3, 5, or 7 (0.60 mmol), Pd(OAc)2 (1.1 mg, 5.0 mumol), S-Phos (4.1 mg, 10.0 mumol), and 2 M LiOH solution (1.0 mL, 2.0 mmol) at room temperature, and the mixture was stirred for 30 min at 80 C under N2 atmosphere. The reaction was quenched by adding water, and then the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. After filtration, the solvent was removed in vacuo, and the residue was purified by silica-gel column chromatography. The solvent was removed in vacuo, and the residue was triturated with Et2O to give biaryl compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; toluene; at 120℃; for 1h;Inert atmosphere; Microwave irradiation; | General procedure: 7-bromo-4-(4-methylpiperazin-1-yl)quinazolin-2-amine (200 mg) and phenylboronic acid (151.2 mg) were dissolved in 3 mL (1:1 EtOH:Toluene) and 2M Na2CO3 (342 muL) was added. The reaction mixture was flushed with N2-gas for 15 minutes. Then, Pd(PPh3)4 (35.86 mg) was added and the resulting mixture was flushed for another 15 minutes with N2-gas. Subsequently, the reaction mixture was typically heated for 1 hour at 120C under microwave irradiation. The reaction mixture was diluted with chloroform and water (200 mL, 1M NaOH) and the aqueous layer was extracted 3 times with ~100 mL chloroform. The combined organic layers were dried over Na2SO4 and evaporation of the solvent gave the crude product that was typically purified by flash chromatography (SiO2) by elution with EtOAc:MeOH:TEA (90:5:5) to yield 143 mg (0.45 mmol, 72%) of the title compound as a solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
149 mg | In a reaction flask charged with Pd(OAc)2 (4.5 mg, 0.02 mmol), potassium iodide (83 mg, 0.5 mmol), and XPhos (28 mg, 0.06 mmol) under argon atmosphere was added, in this following order: anhydrous solvent (2 mL), Et3N (0.4 mL, 3 mmol), 3-chlorothiophene (0.09 mL, 1 mmol) and diisopropylaminoborane (0.3 mL, 2 mmol). The reaction was then heated at 50 C. After total consumption of either starting material, the reaction was cooled at -5 C, quenched with anhydrous MeOH (2 mL) and stirred for 1 h at room temperature. All volatiles were removed under vacuum before adding pinacol (153 mg, 1.3 mmol) in Et20 (2 mL), and the mixture was stirred for 4 h at room temperature. The reaction mixture was diluted with Et20 (10 mL), and the organic phase was washed first with a solution of HC1 (0.1 N, 2x10 mL), followed by an aqueous solution of CuCl2 (50g/L, 3x10 mL), dried over anhydrous Na2S04, filtered and concentrated under vacuum. The crude oil was passed through a pad of silica gel, eluting with Et20. The resulting filtrate was concentrated under vacuum to afford 4,4,5,5-tetramethyl-2- (thiophen-3-yl)-l,3,2-dioxaborolane (149 mg, 71%). 1H NMR (300 MHz, CDC13) delta 7.95 (dd, 1H, J = 2.7, 1.0 Hz), 7.44 (dd, 1H, J = 4.8, 1.0 Hz), 7.36 (dd, 1H, J = 4.8, 2.7 Hz), 1,36 (s, 12H); 13C NMR (100 MHz, CDC13) delta 136.66, 132.06, 125.52, 83.86, 25.04; PiBeta NMR (96 MHz, CDC13) delta ++28.99; MS (EI) tR= 7.258 min; m/z: 210 (M+, 100%). |