Structure of 23112-96-1
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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. : | 23112-96-1 |
Formula : | C8H11BO4 |
M.W : | 181.98 |
SMILES Code : | OB(C1=C(OC)C=CC=C1OC)O |
MDL No. : | MFCD01318987 |
InChI Key : | BKWVXPCYDRURMK-UHFFFAOYSA-N |
Pubchem ID : | 2734343 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 49.25 |
TPSA ? Topological Polar Surface Area: Calculated from |
58.92 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 |
0.77 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-0.62 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.25 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.74 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.17 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.6 |
Solubility | 4.6 mg/ml ; 0.0253 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.59 |
Solubility | 4.7 mg/ml ; 0.0258 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.54 |
Solubility | 5.21 mg/ml ; 0.0286 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 |
No |
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 |
-6.86 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 |
1.0 |
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) |
2.05 |
* 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 |
---|---|---|
96% | With sodium hydroxide; hydroxylamine-O-sulfonic acid; In water; acetonitrile; for 1h;Sonication; | General procedure: Reactions facilitated by sonication were performed on a 1.0 mmol scale. Arylboronic acid 3 (1.0 equiv) and MeCN (5.0 mL) were added to a 25 mL microwave vial equipped with a stir bar, followed by HSA (1.5 equiv) and aq 1 M NaOH (5 equiv). The mixture was capped and set to stir for 5 min, then placed in an ultrasonic cleaner for 30 min (35 kHz, 90 W), at which time the vial was removed and a small aliquot was taken for reaction monitoring via HPLC analysis. The mixture was then placed back in the sonication bath for 30 min. This process was repeated until the reaction had gone to completion, or the reaction failed to progress, as monitored by HPLC. The reaction mixture was diluted with H2O (30 mL) and extracted with EtOAc (2 × 30mL). The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes) to afford the desired amine product 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In tetrahydrofuran; water; at 100℃; for 24h;Inert atmosphere; Schlenk technique; | Under an argon atmosphere, in a Schlenk flask,Followed by loading 3mmol of <strong>[10485-09-3]2-bromoindene</strong> (Shanghai Bi Pharmaceutical Technology Co., Ltd.)1.5 mmol of 2,6-dimethoxyphenylboronic acid (Shanghai Biomedicine Technology Co., Ltd.), 3 mmol% of palladium acetate, 6 mmol% of S-Phos and 3 mmol of potassium phosphate,A mixture of 20 mL of tetrahydrofuran and 10 mL of water was added to dissolve the reaction. The reaction was carried out at 100 C for 24 hours,After cooling, the reaction mixture was extracted with ethyl acetate, the organic phase was dried over anhydrous sodium sulfate, the organic solvent was removed to dryness,Column chromatography on petroleum ether (Rf = 0.8) gave 2- (2,6-dimethoxyphenyl) indene,Yield 79% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Ca. 100% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,2-dimethoxyethane; water; at 90℃; for 3h;Inert atmosphere; | <strong>[1050501-88-6]2-bromo-6-chloropyridin-3-amine</strong> (4.52 g, 21.79 mmol), (2,6-dimethoxyphenyl)boronic acid (4.76 g, 26.1 mmol), Na2CO3 (4.62 g, 43.6 mmol), 1,2-dimethoxyethane (80 mL), and water (40 mL) were added to a 500 mL two-necked round-bottom flask equipped with a magnetic stir bar. The reaction mixture was degassed with N2 for 15 minutes. After this time. Pd(PPh3)4 (1.26 g, 1.09 mmol) was added and the reaction flask was placed into an oil bath and gradually heated to 90 C. for 3 hours. The reaction mixture was then cooled to room temperature (22 C.) and then diluted with ethyl acetate (EtOAc). The resulting mixture was then washed with brine and the separated organic layer were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was triturated with CH2Cl2 to yield the title compound as pale pink solid (4.0 g). The remaining filtrate was purified via flash chromatography on a 200 g column (50-75% EtOAc/Heptanes) to provide 6-chloro-2-(2,6-dimethoxyphenyl)pyridin-3-amine as a white solid (2.5 g) (overall yield 100% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | A mixture of <strong>[16932-45-9]2-bromo-1,3-dimethoxybenzene</strong> 0.018mol was dissolved in 100ml, dry THF, was added 500ml three dried flask, N2Under the protection of -78 reaction 30min, was slowly added dropwise n-butyl lithium 0.027mol, after the completion of the dropping kept -78 reaction 3h, then slowly dropped triisopropyl borate 0.02mol, after the completion of the dropping reaction was held at - 78 reaction 2h, gradually warming to room temperature, the reaction overnight. after the reaction monitored by TLC, the reaction solution was slowly quenched with water, extracted and evaporated to dryness to give (2,6-dimethoxyphenyl) boronic acid (formula III'-1 shown) 0.0144mol, 80% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
240 mg | With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; palladium diacetate; In 1,4-dioxane; toluene; at 100℃; for 6h;Inert atmosphere; | Synthesis Example 1: Synthesis of Exemplary Compound B-4 (0157) (0158) In a 50 mL reaction vessel, 300 mg (0.926 mmol) of XX-1 (5,5′-dibromo-2,2′-bithiophene) and 590 mg (3.24 mmol) of XX-2 were mixed with a toluene/1,4-dioxane (6 ml/6 ml) mixed solvent, and then dissolved oxygen was removed with nitrogen. Subsequently, 8.3 mg (0.037 mmol) of Pd(OAc)2 and 38 mg (0.093 mmol) of 2-dicyclohexyl phosphino-2′,6′-dimethoxy biphenyl (S-Phos), and 1.07 g (4.65 mmol) of tripotassium phosphate were added under a nitrogen atmosphere, heated and refluxed at 100 C., and then reacted for 6 hours. The reaction solution was cooled to room temperature, concentrated under reduced pressure, and then isolated and purified by silica gel chromatography (Mobile phase: Hexane/Chloroform=1/3), whereby B-4 of light yellow solid powder was obtained (240 mg). (0159) As a result of confirming the structure of the compound B-4 by measurement of mass-spectrum (MS) measurement and nuclear magnetic resonance spectrum (NMR) measurement, the molecular weight and the ratio of the NMR peak integrated values were well in agreement with the structure. Specifically, 438 which is M+ of this compound was confirmed by matrix assisted laser desorption ionization mass spectrum (MALDI-MS) measurement. The measurement results of the NMR spectrum are shown below. (0160) 1H-NMR (CDCl3) δ (ppm): 7.41 (d, 2H), 7.23 (t, 2H), 7.18 (d, 2H), 6.65 (d, 4H), 3.86 (s, 12H). |
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