Structure of 3401-47-6
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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. : | 3401-47-6 |
Formula : | C11H9BrO |
M.W : | 237.09 |
SMILES Code : | COC1=C(Br)C2=C(C=CC=C2)C=C1 |
MDL No. : | MFCD00055374 |
InChI Key : | XNIGURFWNPLWJM-UHFFFAOYSA-N |
Pubchem ID : | 72860 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.09 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 58.14 |
TPSA ? Topological Polar Surface Area: Calculated from |
9.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.57 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.83 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.61 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.52 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.63 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.43 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.23 |
Solubility | 0.0141 mg/ml ; 0.0000594 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.72 |
Solubility | 0.0452 mg/ml ; 0.000191 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-5.06 |
Solubility | 0.00207 mg/ml ; 0.00000873 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) |
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) |
Yes |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
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 |
-5.03 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 |
1.0 |
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<2.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.34 |
* 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 potassium phosphate monohydrate; dicyclohexyl(2,6-dimethoxy-3-(2-methoxynaphthalen-1-yl)phenyl)phosphane; palladium diacetate; In tetrahydrofuran; water; at 35℃; for 4h;Inert atmosphere; | A flame dried 250 mL 3-neck round bottomed flask containing a magnetic stir bar was charged with 2-methoxybromonaphthalene (3.56 g, 15.0 mmol), <strong>[133730-34-4]2,4-dimethoxyphenylboronic acid</strong> (5.46 g, 30.0 mmol), and tribasic potassium phosphate monohydrate (8.64 g, 37.5 mmol) under a flow of argon. The vessel was evacuated and backfilled with argon 3 times. A solution of Pd(OAc) (33.7 mg, 0.15 mmol) and L1 (0.104 g, 0.225 mmol) in THF (1.5 mL) was added via syringe to the vessel followed by THF (1.5 mL) and a degassed solution of 2 wt % TPGS-750-M in water (27 mL). The vessel was placed in an oil bath at 35 C. and stirred vigorously. GC/MS and TLC monitoring showed complete consumption of the bromide after 4 h. The crude mixture was transferred to a separatory funnel and extracted with EtOAc (3*20 mL). The combined organic phases were dried over anhydrous Na2SO4 followed by solvent removal in vacuo. The mixture was chromatographed on silica gel eluting with 1:4 diethyl ether:hexanes (Rf=0.20 1:4 diethyl ether:hexanes). The pure product was collected. The impure fractions were collected separately, concentrated and the product was recrystallized from a 1:1 mixture of EtOAc:hexanes yielding an off-white/gray powder (combined 1.54 g, 70%). 1H NMR (500 MHz, chloroform-d) δ 7.87 (d, J=9.0 Hz, 1H), 7.83-7.79 (m, 1H), 7.44-7.40 (m, 1H), 7.37 (d, J=9.0 Hz, 1H), 7.34-7.29 (m, 2H), 7.13 (d, J=7.8 Hz, 1H), 6.67-6.63 (m, 2H), 3.90 (s, 3H), 3.85 (s, 3H), 3.68 (s, 3H). 13C NMR (101 MHz, chloroform-d) δ 160.38, 158.63, 154.47, 133.97, 132.63, 129.04, 128.90, 127.80, 126.03, 125.31, 123.33, 121.77, 117.67, 114.10, 104.40, 99.03, 56.93, 55.66, 55.34. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With tris-(dibenzylideneacetone)dipalladium(0); SPhos; sodium t-butanolate; In 5,5-dimethyl-1,3-cyclohexadiene; at 130 - 140℃;Inert atmosphere; | 1000ml three-necked bottle, in the case of nitrogen 50.0 g of starting material A (211 mmol), 50.7 g of sodium t-butoxide (527 mmol), 0.97 g of Pd2(dba)3 (1.05 mmol),0.87g of S-phos (2.04mmol) and 150ml of xylene, heated to 130 ° C ~ 140 ° C, temperature control 130 ° C ~ 140 ° C slowly added 43.0g of raw material B (211mmol) and 400ml of xylene mixed solution, add dropwise, Keep warm for 15h, TLC detects the completion of the reaction; cools to room temperature, Filter and filter the cake with xylene. The column liquid was steamed to a non-fraction, and the crude yellow solid was purified with toluene. Drying to obtain 53.2 g of intermediate A, yield: 70percent, |
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