Structure of 755027-18-0
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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. : | 755027-18-0 |
Formula : | C7H6BrIO |
M.W : | 312.93 |
SMILES Code : | COC1=CC(I)=CC=C1Br |
MDL No. : | MFCD07780651 |
InChI Key : | PIPWNWZBTWYPJB-UHFFFAOYSA-N |
Pubchem ID : | 12187202 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 53.35 |
TPSA ? Topological Polar Surface Area: Calculated from |
9.23 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.58 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.23 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.06 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
3.44 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.47 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.16 |
Log S (ESOL):? ESOL: Topological method implemented from |
-4.19 |
Solubility | 0.0201 mg/ml ; 0.0000641 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.1 |
Solubility | 0.25 mg/ml ; 0.0008 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.31 |
Solubility | 0.0153 mg/ml ; 0.000049 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) |
No |
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 |
-5.92 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 |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.03 |
* 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 |
---|---|---|
With cesium fluoride;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; at 100.0℃; for 36h; | To a mixture of the product from Step 1, -bromo-4-iodo-2-methoxybenzene (750 mg, 2.4 mmol), CsF (1.09 g, 7.2 mmol), <strong>[850568-47-7](2-amino-4-cyanophenyl)boronic acid hydrochloride</strong> (390 mg, 2.4 mmol), and Pd(PPh3)4 (277 mg, 0.24 mmol) was added DME (15 mL) under nitrogen. It was then heated to 100C. After 36 hours, EtOAc and water were added to the resulting thick red suspension. The organic layer was washed with brine, dried over Na2SO4, and the solvent was removed in vacuo. The residue was purified on silica (gradient EPO <DP n="52"/>elution, 3-50% EtO Ac/hex anes) to yield the title compound as a red oil. LRMS (M+H)+ =303.1. | |
With cesium fluoride;Pd(PPh3)4; In 1,2-dimethoxyethane; water; ethyl acetate; | Step 2: 2-amino-4'-bromo-3'-methoxybiphenyl-4-carbonitrile To a mixture of the product from Step 1, -bromo-4-iodo-2-methoxybenzene (750 mg, 2.4 mmol), CsF (1.09 g, 7.2 mmol), <strong>[850568-47-7](2-amino-4-cyanophenyl)boronic acid hydrochloride</strong> (390 mg, 2.4 mmol), and Pd(PPh3)4 (277 mg, 0.24 mmol) was added DME (15 mL) under N2. It was then heated to 100 C. After 36 h, to the thick red suspension was added EtOAc and water. The organic layer was washed with brine, dried over Na2SO4, and the solvent was removed in vacuo. The residue was purified on silica (gradient elution, 3-50% EtOAc/hex) to yield the title compound as a red oil. LRMS (M+H)+=303.1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; triphenylphosphine;PdCl2(PPh3)2; PdCl2[dppf]; In 1,4-dioxane; ethyl acetate; | Step 2: ethyl 2-(4-bromo-3-methoxyphenyl)cyclohex-1-ene-1-carboxylate To a solution of the product from Step 1, ethyl 2-[(trifluoromethyl)sulfonyl]oxy}cyclohex-1-ene-1-carboxylate (6.65 g, 22.0 mmol) in dioxane (125 mL) was added potassium carbonate (4.56 g, 33.0 mmol), PPh3 (0.346 g, 1.32 mmol), bis(pinacolato)diboron (6.15 g, 24.20 mmol), and PdCl2(PPh3)2 (0.463 g, 0.66 mmol). The mixture was then heated to 80 C. overnight. This solution was then cooled to r.t. and added to a mixture of 1-bromo-4-iodo-2-methoxybenzene (6.86 g, 21.92 mmol), PdCl2(dppf) (0.481 g, 0.657 mmol), potassium carbonate (9.09 g, 65.7 mmol). This mixture was then heated to 80 C. overnight. The mixture was then cooled to r.t., diluted with EtOAc (300 mL) and washed with brine and aqueous KHSO4. The organic layer was then dried over Na2SO4 and the solvent was removed in vacuo. The crude material was then purified on silica (100% DCM) to give impure product which was repurified on silica (gradient elution, 5-20% EtOAc/hexanes) to give the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,4-dioxane; water; at 110℃; | One-neck round bottom flask (One neck r.bf)on1-Bromo-4-iodo-2-methoxybenzene(50 g, 159.7 mmol),Triphenylene-2-ylboronic acid (500 mL / 100 mL), potassium carbonate (44.1 g, 319 mmol), 1,4-dioxane / water (43 mL), tetrakis (triphenylphosphine) palladium (0) (9.2 g, 7.89 mmol) The mixture was refluxed at 110 & lt; 0 & gt; C.Extraction with dichloromethane & lt; RTI ID = 0.0 & gt; MgS04 & lt; / RTI & gt;Filtered through silica gel and concentrated to give the compound 4-5-5. (48 g, 72%). |
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