Structure of 914610-39-2
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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. : | 914610-39-2 |
Formula : | C17H27BN2O4S |
M.W : | 366.28 |
SMILES Code : | O=S(N1CCN(C)CC1)(C2=CC=C(B3OC(C)(C)C(C)(C)O3)C=C2)=O |
MDL No. : | MFCD09746210 |
InChI Key : | TZMSTBRAQGYDJI-UHFFFAOYSA-N |
Pubchem ID : | 23154502 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 25 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.65 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 6.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 106.75 |
TPSA ? Topological Polar Surface Area: Calculated from |
67.46 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 |
1.87 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.24 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.56 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.25 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.78 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.27 |
Solubility | 0.197 mg/ml ; 0.000539 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.91 |
Solubility | 0.452 mg/ml ; 0.00123 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.04 |
Solubility | 0.0334 mg/ml ; 0.0000912 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) |
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 |
-7.21 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) |
3.56 |
* 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 |
---|---|---|
65% | With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In toluene;Inert atmosphere; Reflux; | l-Methyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfonyl]plperazlne (955-2)Pd(PPh3)* (3 g) was added to a mixture of l-(4-bromophenyl sulfonyl)-4-methylpiperazine (20 g, 62.6 mmol), plnacolatodlboron (11 g, 62.6 mmol), and potassium carbonate (17.8 g, 0.13 mol) In toluene (1 L) under nitrogen protection. The mixture was heated under reflux overnight. After cooling to room temperature, the solvent was removed under vacuum. To the residue were added water (500 ml) and ethyl acetate (500 ml). The organic phase was collected, and the water phase was extracted with ethyl acetate (500 ml x2). The organic phases were combined, dried over anhydrous sodium sulfate, and concentrated to afford 1- methyl-4-[4- (4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfonyl]piperazlne (955-2, 15.1 g, yield 65%). LC-MS: 367.2 (M+l). |
65% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In toluene; for 12h;Inert atmosphere; Reflux; | To a mixture of 1-(4-bromophenyl sulfonyl)-4-methylpiperazine (1) (20g, 62.6mmol), pinacolatodiboron (11g, 62.6mmol), and potassium carbonate (17.8g, 0.13mol) in toluene Pd(PPh3)4 (3g) was added (1 L) under nitrogen protection. The mixture was heated under reflux overnight. After cooling to RT, the solvent was removed under vacuum. To the residue were added water (500mL) and EA (500mL). The organic phase was collected, and the water phase was extracted with EA (500mL×2). The organic phases were combined, dried over anhydrous sodium sulfate and concentrated to afford 2 (15.1g, yield 65%). LC-MS: 367.2 (M+l). |
With 1,1'-bis-(diphenylphosphino)ferrocene; potassium acetate;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 90℃; for 8h;Heating; | 1. 2-R2-(4-METHOXVPYRIDIN-2-VL) ETHVLL-6-S-(4-METHYLPIDERAZIN-1-YL-SULFONVL) PHENYLLTH-IMIDAZO- [45-BLPYRIDINE A mixture of 1.12 g of 1- (4-BROMO-BENZENE-SULFONYL)-4-METHYL-PIPERAZINE, 0.978 g of bis- (pinacolato)- diboron, 0.06 g OF 1, 1 -BIS- (DIPHENYLPHOSPHINO)-FERROCENE, 0.077 g of [1,1'-bis (diphenyl- phosphino) ferrocene] palladium-dichloride (complex with CH2CI2), 1.03 g of potassium acetate in 40 ML of degassed dioxane are heated to 90C under N2 FOR 8 hours. To the resulting mixture 15 ml of degassed dioxane, 0.931 g of 2- [2- (4-methoxypyridin-2-yl) ethyl]-6-iodo-3H-imidazo [4,5-b] pyridine (starting material A1), 0.283 g OF TETRAKIS (TRIPHENYLPHOSPHINE)-PALLADIUM (0) and a solution of 0.678 G of potassium carbonate and 0.208 g of lithium chloride in 15 ml of degassed water are added under N2. The mixture is heated to reflux under N2 for 16 hours and, after cooling, addition of water and adjusting the pH to 7, it is extracted three times with DICHLOROMETHANE. The combined organic phases are dried over sodium sulfate, concentrated and the residue is chromatographed on a silica gel column (DICHLOROMETHANELMETHANOL 15-10: 1). Concentration of the chromatographically pure fractions and crystallization of the residue from ETHYLACETATE gives 0.545 g of the title compound as a solid of m. p. 193-195C. The mass spectrum shows the molecular peak MHS at 493.4 Da. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium acetate; bis(pinacol)diborane;1,1'-bis-(diphenylphosphino)ferrocene; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In 1,4-dioxane; at 90℃; for 24h; | 1. 1-(2-lmidazol-1-yl-pyrimidin-5-yl)-1-[4'-(4-methyl-piperazine-1-sulfonyl)-biphenyl-4-yl]- methanone; 492 mg of 1-(4-Bromo-benzenesulfonyl)-4-methyl-piperazine (compound A1 ) are dissolved in 7 ml of oxygen-free dioxane under an atmosphere of dry nitrogen. Subsequently, 429 mg of bis(pinacolato)- diboron, 34 mg of Pd(CI)2(dppf) ' CH2CI2, 26 mg of DPPF (1 ,1'- bis(diphenylphosphino)-ferrocene), and 453 mg of potassium acetate are added. The reaction mixture is heated at 9O0C for 24 hours during which time the former yellowish suspension becomes black (LC-MS monitoring for formation of boronic ester intermediate). Thereafter, 329 mg of 1-(4-bromo-phenyl)-1-(2-imidazol-1-yl-pyrimidin-5-yl)- methanone (compound B1 ), 276 mg of potassium carbonate, 85 mg of lithium chloride, 1 16 mg of Pd(PPh3)4, 11 ml of oxygen-free dioxane, and 11 ml of water are added. The reaction mixture is heated at 9O0C and stirring is continued for 16 hours. Subsequently, the suspension is concentrated in vacuo and co-evaporated twice with 20 ml each of toluene. The resulting crude material is purified by chromatography (eluent: dichloromethane/ethanol 20:1 parts per volume) to afford 165 mg of the title compound as a colorless solid. M. p. 2520C. ESI-MS: 489.3 (MH+). TLC: Rf = 0.56 (dichloromethane/methanol 10:1 parts per volume). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium acetate; palladium diacetate; In N,N-dimethyl-formamide; at 80℃; for 4h;Inert atmosphere; | A 50 mL round bottom flask was charged with 1-(4-bromophenylsulfonyl)-4-methylpiperazine (110 mg, 0.350 mmol), bis-(pinacolato)-diboron (93 mg, 0.37 mmol), palladium acetate (6 mg, 0.02 mmol), and potassium acetate (103 mg, 1.05 mmol) in N,N-dimethylformamide (6 mL). The mixture was degassed by gently bubbling argon through the solution for 30 minutes at room temperature. The mixture was then heated at 80 C. under argon until the reaction was complete (4 hours). The required product, 1-methyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]sulfonyl-piperazine, and the bi-aryl product, 4-(4-methylpiperazin-1-ylsulfonyl)phenyl-phenylsulfonyl-4-methylpiperazine, were obtained in a ratio of 1:2 as indicated by LC/MS analysis. |
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