Structure of 397843-58-2
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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. : | 397843-58-2 |
Formula : | C11H16BNO3 |
M.W : | 221.06 |
SMILES Code : | OB(C1=CC=CC(CN2CCOCC2)=C1)O |
MDL No. : | MFCD08060623 |
InChI Key : | VTSDPGUSDVMXDN-UHFFFAOYSA-N |
Pubchem ID : | 11031409 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P280-P305+P351+P338-P310 |
Num. heavy atoms | 16 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.45 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 66.24 |
TPSA ? Topological Polar Surface Area: Calculated from |
52.93 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 |
0.29 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
-1.33 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.27 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.35 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-0.33 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.47 |
Solubility | 7.44 mg/ml ; 0.0337 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.96 |
Solubility | 24.0 mg/ml ; 0.109 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.89 |
Solubility | 2.87 mg/ml ; 0.013 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 |
-7.44 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) |
1.94 |
* 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 |
---|---|---|
90% | 3-(Morpholinomethyl)phenylboronic acid (8c). White solid (81% yield by mass; 90% yield by 1H NMR with EtOAc int. std.); 1H NMR (300 MHz, 5% D2O in CD3OD) delta7.69-7.64 (m, 2H), 7.39-7.36 (m, 1H), 7.32-7.27 (m, 1H), 3.68 (m, 4H), 3.53 (s, 2H), 2.47 (m, 4H); 13C NMR (75 MHz, 5% D2O in CD3OD) delta141.1, 136.7, 136.4, 134.1, 132.8, 128.6, 67.5, 64.4, 54.5; IR (CH2Cl2 cast) 3405, 3047, 2957, 2857, 2808, 1652, 1602 cm-1; HRMS (ES, m/z) calcd for C11H17BNO3 (M+H)+222.1296, found 222.1297. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58.13% | With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 120℃; for 1h;Inert atmosphere; Microwave irradiation; | 24: 3-(l-Isopropyltriazol-4-yl)-5-[3 (morpholinomethyl) phenyl] pyridin CS2CO3 (858 mg, 2.64 mmol) was added to a solution of <strong>[397843-58-2](3-(morpholinomethyl)phenyl)boronic acid</strong> (250 mg, 0.88 mmol) and 5-bromo-3-(l-isopropyl-lH-[l,2,3]triazol-4-yl)-pyridin-2- ylamine (215 mg, 0.97 mmol) in dioxane: water (8 mL: 4 mL) degassed the reaction mixture for 10 min with nitrogen. Then added Pd(PPh3)4 (50 mg, 0.044 mmol), degassed the reaction mixture for additional 10 min with nitrogen, the reaction mixture was heated to 120 C in microwave for lh. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (2x 30mL). Combined organic layers was dried over Na2S04 and concentrated under reduced pressure. Crude product was purified by silica (100-200 mesh) column eluted with 80-90% ethyl acetate in pet-ether to afford 195 mg (Yield: 58.13 %) of the title compound as a pale yellow solid. Product was converted to its HC1 salt by using HC1 in ether (2M) to afford 202 mg as a pale yellow solid. 'HNMR (DMSO-dg, 400 MHz, TMS) delta: 11.60 (lH, br, s), 9.51 (IH, s), 9.04 (IH, s), 8.54 (3H, br, s), 8.37 (IH, s), 7.89-7.88 (IH, d), 7.60-7.52 (2H, m), 4.99-4.92 (IH, m), 4.44 (2H, s), 3.93 (4H, s), 3.23 (2H, s), 3.16 (2H, br, s), 1.60-1.58 (6H, d). LC-MS: mlz = 379.5 (MH+), tR = 0.36, method A. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
16.7% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 100℃; for 18h;Inert atmosphere; | 29: 3-(5-cyclopropyl-l, 3, 4-oxadiazol-2-yl)-5-[ 3-(morpholinomethyl)phenyl]pyridin To a solution of 5-bromo-3-(5-cyclopropyl-[l,3,4]oxadiazol-2-yl)-pyridin-2-ylamine (400 mg; 1.42 mmol) in dioxane (10 mL) and water (6 mL) were added K2CO3 (587 mg; 4.26 mmol), (3- (morpholinomethyl)phenyl)boronic acid (348 mg; 1.56 mmol) in a sealed tube. The reaction mixture was degassed with argon for 30 min, then added Pd(PPh3)4 (82.0 mg; 0.07 mmol) to the reaction mixture. The reaction mixture was stirred for 18 h at 100 C. The reaction mixture was diluted with water (50 mL) extracted with ethyl acetate (2 X 50 mL) and organic layer was washed with brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure. Crude compound was purified by column chromatography using 100-200 mesh silica gel and eluted with 100 % ethyl acetate, which is further purified by washing with 30 % chloroform in hexane to afford 90 mg (Yield: 16.7 %) of the title compound, as a yellow colour solid. FontWeight="Bold" FontSize="10" HNMR (DMSO-dg, 400 MHz, TMS) delta: 8.52-8.51 (1H, d), 8.20-8.19 (1H, d), 7.58-7.54 (2H, m), 7.43-7.39 (1H, t), 7.35 (2H, s), 7.31-7.28 (1H, d), 3.59-3.54 (6H, m), 2.40-2.30 (5H, m), 1.20-1.15 (4H, m). LCMS conditions: Column BEH C 18 (2.1 x 50 mm) 1.7 mu M-Phase A 5 mM NH4OAC in H20 M-Phase B ACN T/%B 0/03, 1.5/45, 2.5/45, 3.2/95, 4.7/95, 5/03 Flow 0.4 ml/min Diluent MeOH Drift Tube Temp 55 C Gas Pressure : 30psi Nebulizer Temp : 65% Gain : 500 Purity : 97.21 % tPv = 2.10 min, m/z= 378.2[M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44.1% | With tripotassium phosphate; In tetrahydrofuran; water; at 85℃; for 2.5h;Inert atmosphere; Sonication; | Intermediate 14A (60 mg, 0.106 mmol), <strong>[397843-58-2](3-(morpholinomethyl)phenyl)boronic acid</strong> (35.3 mg, 0.160 mmol) and tripotassium phosphate (113 mg, 0.532 mmol) were combined in a vial. THF (1.5 mL) and water (0.2 mL) were added and the mixture was degassed by bubbling argon while sonicated. Tetrakistriphenylphosphine (12.31 mg,10.65 .imol) was added and the degassing procedure was repeated. The mixture was heated at 85 C for 2.5h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (5 mL), water (2 mL) and the layers were mixed and then separated. The organic layer was dried over MgSO4 and concentrated. The crude product was 5purified by silica gel chromatography eluting with a gradient of 0-10% MeOH in DCM (w/ 0.5% NH4OAc added to each eluting solvent). The solid obtained was triturated with ethyl acetate to afford Example 14 (22.7 mg, 44.1% yield) as a white solid. LCMS (M+H) = 460.26. Retention time 0.71 mi LCMS Method B. |
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