Structure of 1012085-50-5
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CAS No. : | 1012085-50-5 |
Formula : | C17H27B2NO4 |
M.W : | 331.02 |
SMILES Code : | CC1(C)C(C)(C)OB(C2=CN=CC(B3OC(C)(C)C(C)(C)O3)=C2)O1 |
MDL No. : | MFCD12923191 |
InChI Key : | PJLRGJDKNWXNRI-UHFFFAOYSA-N |
Pubchem ID : | 56973239 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 24 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.71 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 97.19 |
TPSA ? Topological Polar Surface Area: Calculated from |
49.81 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 |
2.82 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.68 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.47 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.28 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.25 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.72 |
Solubility | 0.0628 mg/ml ; 0.00019 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.52 |
Solubility | 0.0992 mg/ml ; 0.0003 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.2 |
Solubility | 0.00211 mg/ml ; 0.00000637 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) |
Yes |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
Yes |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.32 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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
3.65 |
* 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 |
---|---|---|
With potassium acetate;palladium diacetate; In tetrahydrofuran; for 5h;Reflux; Inert atmosphere;Product distribution / selectivity; | Example 3; Synthesis of Compound of Formula IV To a flame dried 3-neck round bottom flask fitted with a condenser, a nitrogen inlet, and a rubber septum was added PcyBiPh (84 mg, 0.20 mmol) and Pd(OAc)2 (19.0 mg, 0.080 mmol). The flask was then protected from the atmosphere and was charged with anhydrous THF (10 mL) and the solution was degassed by purging N2 through the stirred solution. After 15 minutes, the reaction mixture was charged with 3,5-dibromopyridine (0.315 g, 1.33 mmol), pinacolate diborane (0.338 g, 2.66 mmol), dry KOAc (0.217 g, 12.2 mmol), and the mixture was heated at reflux for 5 hours. The reaction mixture was cooled to room temperature and charged with the compound 2, (1.60 g, 3.2 mmol), Na2CO3 (1.20 g, 11.3 mmol), Cs2CO3 (1.10 g, 3.38 mmol), and degassed H2O (0.25 mL). The mixture was then heated at reflux for 20 hours, after which it was cooled to room temperature and concentrated to dryness. The crude material thus obtained was suspended in H2O, collected by filtration, and washed with H2O. The dried solid was chromatographed through SiO2 (3-5% MeOH/CH2Cl2) to give compound of formula IV as a colorless solid. Yield: 0.851 g, 64%. 1H NMR (400 MHz, CD3OD/CD2Cl2, 25 C.) delta7.46 (m, 4H), 7.66 (t, 4H), 7.72 (m, 6H), 7.83 (m, 2H), 7.90 (m, 2H), 8.07 (m, 10H), 8.26 (m, 4H), 8.33 (t, 1H), 8.44 (t, 4H), 8.54 (m, 4H), 8.89 (m, 4H), 8.93 (m, 2H). | |
With potassium acetate;palladium diacetate; CyJohnPhos; In tetrahydrofuran; for 5h;Inert atmosphere; Reflux; | EXAMPLE 3: synthesis of compound of formula IV[0040] To a flame dried 3-neck round bottom flask fitted with a condenser, a nitrogen inlet, and a rubber septum was added PcyBiPh (84 ing, 0.20 mmol) and Pd(OAc)2 (19.0 mg, 0.080 mmol). The flask was then protected from the atmosphere and was charged with anhydrous THF (10 mL) and the solution was degassed by- purging N2 through the stirred solution. After 15 minutes,, the reaction mixture was charged with 3.5-dibromopyridine (0.315 g, 1.33 mmol), pinacolate diborane (0.338 g, 2.66 mmol), dry KOAc (0.217 g, 12.2 mmol), and the mixture was heated at refiux for 5 hours. The reaction mixture was cooled to room temperature and charged with the compound 2, (1.60 g, 3.2 mmol), Na3CO3 (1.20 g, 11.3 mmolX Cs2CO3 (1.10 g, 3.38 mmol). and degassed H2O (0.25 mL). The mixture was then heated at refiux for 20 hours, after which it was cooled to room temperature and concentrated to dryness. The crude materia. thus obtained was suspended in H2O. collected by filtration, and washed with H2O. The dried solid was chromatographed through Sitheta2 (3-5% MeOH/CH2Cl2) to give compound of formula IV as a colorless solid. Yield: 0.851 g, 64%. 1H NMR (400 MH/, CD3OD/CD2Cl2, 25 C) 61.46 Cm, 4H), 7.66 (t, 4H), 7.72 (m, 6H), 7.83 (m, 2H), 7.90 (m, 2H), 8.07 (m, 10H), 8.26 (m, 4H), 8.33 (t, 1H), 8.44 (t, 4H), 8.54 (n% 4H), 8.89 (m, 4H), 8.93 (m, 2H). | |
With potassium acetate;palladium diacetate; CyJohnPhos; In 1,4-dioxane; at 110℃; for 3h;Inert atmosphere; | EXAMPLE 9: synthesis of compound of formula XJ0047J To a schlenk tube was charged 3,5-dibromopyridine (50 mg, 0.21 mmol), pinacolate diborane (0.117 g, 0.462 mmol), dry KOAc (0.1 g, 1 mmol), ligandPCvBin (6.7 mgt 0.0 3 mg, 0.03 mmoL 3%). The schlenk tube was evacuated and filled with argon three times. The schlenk was placed in an argon atmosphere. Anhydrous dioxane (6 tnL) was added. The flask was then heated at 1 K) C for 3 hours under argon atmosphere. Then compound 3 (0.25 g, 0.5 mmol), dry KOAc (0,1 g, 1 mmolX, ligand PCyBin (6.7 mg, 0,017 mmol, 4%) and Pd(OAc)Z (3 nig, 0.013 mmol, 3%) and 5 ml dioxane were added into above reaction solution, then reiluxed at 1 10 X overnight under argon atmosphere. Then cooled to ambient temperature. Distilled water (30 mL) was added via a funnel, and the resulting mixture was filtered on a Bchner funnel. The filtrate was transferred to a separatory funnel and extracted with CIhCh O x 30 mL). The combined organic phases were dried over Na^SO4, filtered on filter paper and concentrated to dryness by rotary evaporation (30 C, 25 mmHg). The resulting yellow solid was purified by column chromatography affording as a white solid 94 mg (45%). 1H NMR (400 MHz, CDCI3) delta 8.94 (m, 6H), 8.64 (m, 4H), 8.20 (m, 1H), 7.97-7.91 (m, 16H). 7.82-7.63 (m, 18H), 7.41 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate; caesium carbonate;ligand PCyBiPh; In water; for 20h;Reflux; Inert atmosphere; | Example 3; Synthesis of Compound of Formula IV To a flame dried 3-neck round bottom flask fitted with a condenser, a nitrogen inlet, and a rubber septum was added PcyBiPh (84 mg, 0.20 mmol) and Pd(OAc)2 (19.0 mg, 0.080 mmol). The flask was then protected from the atmosphere and was charged with anhydrous THF (10 mL) and the solution was degassed by purging N2 through the stirred solution. After 15 minutes, the reaction mixture was charged with 3,5-dibromopyridine (0.315 g, 1.33 mmol), pinacolate diborane (0.338 g, 2.66 mmol), dry KOAc (0.217 g, 12.2 mmol), and the mixture was heated at reflux for 5 hours. The reaction mixture was cooled to room temperature and charged with the compound 2, (1.60 g, 3.2 mmol), Na2CO3 (1.20 g, 11.3 mmol), Cs2CO3 (1.10 g, 3.38 mmol), and degassed H2O (0.25 mL). The mixture was then heated at reflux for 20 hours, after which it was cooled to room temperature and concentrated to dryness. The crude material thus obtained was suspended in H2O, collected by filtration, and washed with H2O. The dried solid was chromatographed through SiO2 (3-5% MeOH/CH2Cl2) to give compound of formula IV as a colorless solid. Yield: 0.851 g, 64%. 1H NMR (400 MHz, CD3OD/CD2Cl2, 25 C.) delta7.46 (m, 4H), 7.66 (t, 4H), 7.72 (m, 6H), 7.83 (m, 2H), 7.90 (m, 2H), 8.07 (m, 10H), 8.26 (m, 4H), 8.33 (t, 1H), 8.44 (t, 4H), 8.54 (m, 4H), 8.89 (m, 4H), 8.93 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium acetate;palladium diacetate; In 1,4-dioxane; at 110℃;Reflux; Inert atmosphere; | Example 9; Synthesis of Compound of Formula X To a schlenk tube was charged 3,5-dibromopyridine (50 mg, 0.21 mmol), pinacolate diborane (0.117 g, 0.462 mmol), dry KOAc (0.1 g, 1 mmol), ligand PCyBin (6.7 mg, 0.017 mmol, 4%) and Pd(OAc)2 (3 mg, 0.013 mmol, 3%). The schlenk tube was evacuated and filled with argon three times. The schlenk was placed in an argon atmosphere. Anhydrous dioxane (6 mL) was added. The flask was then heated at 110 C. for 3 hours under argon atmosphere. Then compound 3 (0.25 g, 0.5 mmol), dry KOAc (0.1 g, 1 mmol), ligand PCyBin (6.7 mg, 0.017 mmol, 4%) and Pd(OAc)2 (3 mg, 0.013 mmol, 3%) and 5 ml dioxane were added into above reaction solution, then refluxed at 110 C. overnight under argon atmosphere. Then cooled to ambient temperature. Distilled water (30 mL) was added via a funnel, and the resulting mixture was filtered on a Buechner funnel. The filtrate was transferred to a separatory funnel and extracted with CH2Cl2 (3×30 mL). The combined organic phases were dried over Na2SO4, filtered on filter paper and concentrated to dryness by rotary evaporation (30 C., 25 mmHg). The resulting yellow solid was purified by column chromatography affording as a white solid 94 mg (45%). 1H NMR (400 MHz, CDCl3) delta8.94 (m, 6H), 8.64 (m, 4H), 8.20 (m, 1H), 7.97-7.91 (m, 16H), 7.82-7.63 (m, 18H), 7.41 (m, 4H). | |
With potassium acetate;palladium diacetate; CyJohnPhos; In 1,4-dioxane; at 110℃;Inert atmosphere; | EXAMPLE 9: synthesis of compound of formula XJ0047J To a schlenk tube was charged 3,5-dibromopyridine (50 mg, 0.21 mmol), pinacolate diborane (0.117 g, 0.462 mmol), dry KOAc (0.1 g, 1 mmol), ligandPCvBin (6.7 mgt 0.0 3 mg, 0.03 mmoL 3%). The schlenk tube was evacuated and filled with argon three times. The schlenk was placed in an argon atmosphere. Anhydrous dioxane (6 tnL) was added. The flask was then heated at 1 K) C for 3 hours under argon atmosphere. Then compound 3 (0.25 g, 0.5 mmol), dry KOAc (0,1 g, 1 mmolX, ligand PCyBin (6.7 mg, 0,017 mmol, 4%) and Pd(OAc)Z (3 nig, 0.013 mmol, 3%) and 5 ml dioxane were added into above reaction solution, then reiluxed at 1 10 X overnight under argon atmosphere. Then cooled to ambient temperature. Distilled water (30 mL) was added via a funnel, and the resulting mixture was filtered on a Bchner funnel. The filtrate was transferred to a separatory funnel and extracted with CIhCh O x 30 mL). The combined organic phases were dried over Na^SO4, filtered on filter paper and concentrated to dryness by rotary evaporation (30 C, 25 mmHg). The resulting yellow solid was purified by column chromatography affording as a white solid 94 mg (45%). 1H NMR (400 MHz, CDCI3) delta 8.94 (m, 6H), 8.64 (m, 4H), 8.20 (m, 1H), 7.97-7.91 (m, 16H). 7.82-7.63 (m, 18H), 7.41 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium carbonate; caesium carbonate; In tetrahydrofuran; water; for 20h;Reflux; | EXAMPLE 3: synthesis of compound of formula IV[0040] To a flame dried 3-neck round bottom flask fitted with a condenser, a nitrogen inlet, and a rubber septum was added PcyBiPh (84 ing, 0.20 mmol) and Pd(OAc)2 (19.0 mg, 0.080 mmol). The flask was then protected from the atmosphere and was charged with anhydrous THF (10 mL) and the solution was degassed by- purging N2 through the stirred solution. After 15 minutes,, the reaction mixture was charged with 3.5-dibromopyridine (0.315 g, 1.33 mmol), pinacolate diborane (0.338 g, 2.66 mmol), dry KOAc (0.217 g, 12.2 mmol), and the mixture was heated at refiux for 5 hours. The reaction mixture was cooled to room temperature and charged with the compound 2, (1.60 g, 3.2 mmol), Na3CO3 (1.20 g, 11.3 mmolX Cs2CO3 (1.10 g, 3.38 mmol). and degassed H2O (0.25 mL). The mixture was then heated at refiux for 20 hours, after which it was cooled to room temperature and concentrated to dryness. The crude materia. thus obtained was suspended in H2O. collected by filtration, and washed with H2O. The dried solid was chromatographed through Sitheta2 (3-5% MeOH/CH2Cl2) to give compound of formula IV as a colorless solid. Yield: 0.851 g, 64%. 1H NMR (400 MH/, CD3OD/CD2Cl2, 25 C) 61.46 Cm, 4H), 7.66 (t, 4H), 7.72 (m, 6H), 7.83 (m, 2H), 7.90 (m, 2H), 8.07 (m, 10H), 8.26 (m, 4H), 8.33 (t, 1H), 8.44 (t, 4H), 8.54 (n% 4H), 8.89 (m, 4H), 8.93 (m, 2H). |
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