Structure of 870521-33-8
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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. : | 870521-33-8 |
Formula : | C8H12BN3O3 |
M.W : | 209.01 |
SMILES Code : | OB(O)C1=CN=C(N=C1)N1CCOCC1 |
MDL No. : | MFCD07375148 |
InChI Key : | KFYQOIHLZBDFBU-UHFFFAOYSA-N |
Pubchem ID : | 46864007 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.5 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 57.58 |
TPSA ? Topological Polar Surface Area: Calculated from |
78.71 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 |
-0.81 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-2.39 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.74 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-1.68 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-1.32 |
Log S (ESOL):? ESOL: Topological method implemented from |
-0.79 |
Solubility | 33.9 mg/ml ; 0.162 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.36 |
Solubility | 90.5 mg/ml ; 0.433 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.74 |
Solubility | 38.4 mg/ml ; 0.184 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
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 |
-8.15 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) |
2.27 |
* 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 |
---|---|---|
70% | With triethylamine In ethanol at 20℃; for 1 h; | 2-Chloropyrimidin-5-ylboronic acid (1 g, 6.32 mmol), morpholine (2.19 mL,25.26 mmol) and triethylamine (0.88 mL, 6.32 mmol) were stirred in ethanol (25 mL) at20°C for 1 h. Water (50 mL) was slowly added to the reaction mixture. The resultingprecipitate was filtered and washed with water to afford the title compound (950 mg,70percent) as a cream solid. H (250 MHz, DMSO-d6) 8.63 (s, 2H), 8.05 (s, 2H), 3.68 (ddd, J23.4, 5.7, 3.9 Hz, 8H). |
70% | With triethylamine In ethanol at 20℃; for 1 h; | A solution of (2-chloropyrimidin-5-yl)boronic acid (1 g, 6.32 mmol), morpholine (2.19 mL, 25.26 mmol) and triethylamine (0.9 mL, 6.32 mmol) in ethanol (25 mL) was stirred at 20°C for 1 h. Water (50 mL) was slowly added to the reaction mixture to form a precipitate that was collected by filtration, to afford the title compound (950 mg, 70percent) ascream solid. H (250 MHz, DMSO-d6) 8.63 (s, 2H), 8.05 (s, 2H), 3.68 (ddd, J23.4, 5.7,3.9 Hz, 8H). LCMS m/z 210 [M+H]. |
70% | With triethylamine In ethanol at 20℃; for 1 h; Inert atmosphere | A solution of (2-chloropyrimidin-5-yl)boronic acid (1 g, 6.32 mmol), morpholine (2.19 mL, 25.26 mmol) and triethylamine (0.9 mL, 6.32 mmol) in ethanol (25 mL) was stirred at 20°C for 1 h. Water (50 mL) was slowly added to the reaction mixture to form a precipitate that was collected by filtration, to afford the title compound as a cream solid (950 mg, 70percent). δΗ (250 MHz, DMSO-d6) 8.63 (s, 2H), 8.05 (s, 2H), 3.68 (ddd, J23.4, 5.7, 3.9 Hz, 8H). LCMS(ES+) 210 (M+H)+. |
70% | With triethylamine In ethanol at 20℃; for 1 h; | A solution of (2-chloropyrimidin-5-yl)boronic acid (1 g, 6.32 mmol), morpholine (2.19 mL, 25.26 mmol) and triethylamine (0.9 mL, 6.32 mmol) in ethanol (25 mL) was stirred at 20°C for 1 h. Water (50 mL) was slowly added to the reaction mixture to form a precipitate that was collected by filtration, to afford the title compound as a cream solid (950 mg, 70percent). δΗ (250 MHz, DMSO-d6) 8.63 (s, 2H), 8.05 (s, 2H), 3.68 (ddd, J23.4, 5.7, 3.9 Hz, 8H). LCMS(ES+) 210.0 (M+H)+. |
70% | With triethylamine In ethanol at 20℃; for 1 h; | A solution of(2-chloropyrimidin-5-yl)boronic acid (1 g, 6.32 mmol), morpholine (2.19 mL, 25.26 mmol) and triethylamine (0.9 mL, 6.32 mmol) in ethanol (25 mL) was stirred at 20°C for 1 h. Water (50 mL) was slowly added to the reaction mixture to form a precipitate that was collected by filtration, to afford the title compound as a cream solid(950 mg, 70percent). oH (250 MHz, DMSO-d6) 8.63 (s, 2H), 8.05 (s, 2H), 3.68 (ddd, J23.4, 5.7, 3.9 Hz, 8H). LCMS(ES) 210 (M+H). |
68% | With triethylamine In ethanol at 80℃; for 5 h; | A mixture of 2-chloropyrimidin-5-ylboronic acid (3 g, 19.0 mmol), morpholine (1.66 mL, 19 mmol) and triethylamine (1.67 mL, 19.19 mmol) in EtOH (20 mL) was stirred at 80°C for 5 h. LCMS indicated completion of the reaction. The reaction mixturewas concentrated in vacuo and the residue was taken up in ethanol (approximately 5 mL). Diethyl ether was added, and the triethylamine hydrochloride salt that crystallised out was filtered and discarded. The filtrate was concentrated in vacuo and water (approximately 10 mL) was added. The mixture was placed in a refrigerator for 1 h, after which time the resulting solid was filtered off, washed with the minimum amount of water and dried bysuction, to give the title compound (2.7 g, 68percent) as an off-white solid. oH (DMSO-d6)8.64 (s, 2H), 8.08 (s, 2H), 3.73 (m, 4H), 3.65 (m, 4H). LCMS (ES+) 210 (M+H), RT0.15 minutes. |
68% | With triethylamine In ethanol at 80℃; for 5 h; | A mixture of 2-chloropyrimidin-5-ylboronic acid (3 g, 19.0 mmol), morpholine (1.66 mL, 19.0 mmol) and triethylamine (1.67 mL, 19.2 mmol) in EtOH (20 mL) wasstirred at 80°C for 5 h. The reaction mixture was concentrated in vacuo and the residue was taken up in Et20 (approximately 5 mL). Et20 was added, and the triethylamine hydrochloride salt that crystallised out was filtered and discarded. The filtrate was concentrated in vacuo and water (approximately 10 mL) was added. The mixture was placed in a refrigerator for 1 h, after which time the resulting solid was filtered off, washed with the minimum amount of water and dried by suction, to give the title compound (2.7 g, 68percent) as an off-white solid. oH (DMSO-d6) 8.64 (s, 2H), 8.08 (s, 2H), 3.73 (m, 4H), 3.65 (m, 4H). LCMS (ESj 210 (M+H), RT 0.15 minutes. |
68% | With triethylamine In ethanol at 80℃; for 5 h; | INTERMEDIATE 4 2-(Morpholin-4-yl)pyrimidin-5 -ylboronic acidA mixture of 2-chloropyrimidin-5-ylboronic acid (3.0 g, 19.0 mmol), morpholine (1.66 mL, 19.0 mmol) and triethylamine (1.67 mL, 19.2 mmol) in EtOH (20 mL) was stirred at 80°C for 5 h. The reaction mixture was concentrated in vacuo and the residue was taken up in Et20 (approximately 5 mL). Et20 was added, and the triethylamine hydrochloride salt that crystallised out was filtered and discarded. The filtrate was concentrated in vacuo and water (approximately 10 mL) was added. The mixture was placed in a refrigerator for 1 h, after which time the resulting solid was filtered off,washed with the minimum amount of water and dried by suction, to give the title compound (2.7 g, 68percent) as an off-white solid. H (400 MHz, DMSO-d6) 8.64 (s, 2H), 8.08 (s, 2H), 3.73 (m, 4H), 3.65 (m, 4H). LCMS (ESj 210 (M+H), RT 0.15 minutes. |
68% | With triethylamine In ethanol at 80℃; for 5 h; | INTERMEDIATE 5 2- (Morpholin-4- yl)p yrimidin- 5 - ylboronic acid A mixture of 2-chloropyrimidin-5-ylboronic acid (3 g, 19.0 mmol), morpholine (1.66 mL, 19.0 mmol) and triethylamine (1.67 mL, 19.2 mmol) in EtOH (20 mL) was stirred at 80°C for 5 h. The reaction mixture was concentrated in vacuo and the residue was taken up in Et20 (approximately 5 mL). Et20 was added, and the triethylamine hydrochloride salt that crystallised out was filtered and discarded. The filtrate was concentrated in vacuo and water (approximately 10 mL) was added. The mixture was placed in a refrigerator for 1 h, after which time the resulting solid was filtered off, washed with the minimum amount of water and dried by suction, to give the title compound (2.7 g, 68percent) as an off-white solid. δΗ (DMSO-d6) 8.64 (s, 2H), 8.08 (s, 2H), 3.73 (m, 4H), 3.65 (m, 4H). LCMS (ES+) 210 (M+H)+, RT 0.15 minutes. |
68% | With triethylamine In ethanol at 80℃; for 5 h; | INTERMEDIATE 3 2-(Morpholin-4-yl)pyrimidin-5 -ylboronic acid A mixture of 2-chloropyrimidin-5 -ylboronic acid (3.0 g, 19.0 mmol), morpholine (1.66 mL, 19.0 mmol) and triethylamine (1.67 mL, 19.2 mmol) in EtOH (20 mL) was stirred at 80°C for 5 h. The reaction mixture was concentrated in vacuo and the residue was taken up in Et20 (approximately 5 mL). Et20 was added, and the triethylamine hydrochloride salt that crystallised out was filtered and discarded. The filtrate was concentrated in vacuo and water (approximately 10 mL) was added. The mixture was placed in a refrigerator for 1 h, after which time the resulting solid was filtered off, washed with the minimum amount of water and dried by suction, to give the title compound (2.7 g, 68percent) as an off-white solid. δΗ (400 MHz, DMSO-dg) 8.64 (s, 2H), 8.08 (s, 2H), 3.73 (m, 4H), 3.65 (m, 4H). LCMS (ES+) 210 (M+H)+, RT 0.15 minutes. |
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