Structure of 104901-43-1
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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. : | 104901-43-1 |
Formula : | C9H9BrO2 |
M.W : | 229.07 |
SMILES Code : | C1=C(C=CC(=C1Br)C)C(OC)=O |
MDL No. : | MFCD00144769 |
InChI Key : | MASRAGFWFYHMFI-UHFFFAOYSA-N |
Pubchem ID : | 7015747 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 50.39 |
TPSA ? Topological Polar Surface Area: Calculated from |
26.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.54 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.83 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.54 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.97 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.84 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.74 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.28 |
Solubility | 0.12 mg/ml ; 0.000523 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.04 |
Solubility | 0.209 mg/ml ; 0.000912 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.72 |
Solubility | 0.0436 mg/ml ; 0.000191 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 |
Yes |
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) |
Yes |
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 |
-5.69 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 |
0.0 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) |
1.63 |
* 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 |
---|---|---|
71% | With sodium carbonate;dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); In 1,2-dimethoxyethane; water; toluene; for 24h;Heating / reflux; | [4-(Benzyloxy)-2,6-dimethylphenyl]boronic acid (354 mg, 1.38 mmol) and methyl 3-bromo-4-methylbenzoate (229 mg, 1.00 mmol) were dissolved in a mixture of 2 M aqueous sodium carbonate solution (1.38 mL), toluene (10 mL) and 1,2-dimethoxyethane (1 mL), the air was substituted with argon gas, and dicyclohexyl(2',6'-dimethoxybiphenyl-2-yl)phosphine (32.8 mg, 0.08 mmol) and tris(dibenzylideneacetone)dipalladium(0) (18.3 mg, 0.02 mmol) were added. The reaction mixture was heated under reflux for one day. After cooling the reaction mixture, brine was added, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane-hexane/ethyl acetate=9/1) to give the title compound (255 mg, yield 71%) as a colorless oil. MS m/z 361 (MH+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2?,4?,6?-tri-1-propyl-1,1?-biphenyl][2-(2-aminoethyl)phenyl]palladium(II); caesium carbonate; In 1,4-dioxane; at 120℃; for 1.5h;Inert atmosphere; | To a solution of <strong>[66521-66-2]4-(pyridin-3-yl)pyrimidin-2-amine</strong> (2 g, 11.62 mmol, 1.00 equiv) and methyl 3-bromo-4-methylbenzoate (2.92 g, 12.75 mmol, 1.10 equiv) in dioxane (20 mL) were added CS2CO3 (5.3 g, 16.27 mmol, 1.40 equiv) and BrettPhos precatalyst (32 mg, 0.04 mmol, 0.03 equiv). The flask was evacuated and flushed three times with nitrogen. The resulting solution was stirred for 1.5 h at 120 °C. The reaction mixture was cooled to 20 °C. The resulting solution was diluted with EtOAc (50 mL). The solids were filtered out. The filtrate was washed with brine (3 x 30 mL). The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was washed with ethyl acetate/petroleum ether (1 :3). The solid was collected by filtration to afford 3.0 g (81percent) of methyl 4-methyl-3-[[4-(pyridin-3-yl)pyrimidin-2-yl]amino]benzoate as an off-white solid. NMR (400 MHz, CDCh) delta: 9.33-9.34 (m, 1H), 9.03-9.04 (m, 1H), 8.75-8.77 (m, 1H), 8.59-8.45 (m, 2H), 7.74-7.77 (m, 1H), 7.46-7.50 (m, 1H), 7.35-7.23 (m, 1H), 7.11 (s, 1H), 3.98 (s, 3H), 2.44 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 90℃; for 16h;Inert atmosphere; | Methyl 3-bromo-4-methylbenzoate (3 mL, 19.2 mmol) was dissolved in 1,4-dioxane (96 mL), and bis(pinacolato)diboron (7.31 g, 28.2 mmol), potassium acetate (5.65 g, 57.6 mmol), and Pd(dppf)Cl2 (2.8 g, 3.84 mmol) were added thereto. The resulting mixture was replaced with argon, and stirred at 90C for 16 hours. The mixture was cooled to room temperature, and water was added. Then, the mixture was extracted with EtOAc. An organic layer was dried over magnesium sulfate, concentrated, and then purified using silica gel chromatography to obtain the title compound (off-white solid, 4.46 g, and 84% yield). 1H NMR (300 MHz, CDCl3) delta 8.40 (d, 1H), 7.97 (dd, 1H), 7.23 (d, 1H), 3.94-3.87 (m, 3H), 2.58 (s, 3H), 1.35 (d, 12H). |
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