Structure of 175883-60-0
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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. : | 175883-60-0 |
Formula : | C7H8BClO3 |
M.W : | 186.40 |
SMILES Code : | COC1=C(Cl)C=C(C=C1)B(O)O |
MDL No. : | MFCD04039888 |
InChI Key : | VUTJHOWRPUPHIG-UHFFFAOYSA-N |
Pubchem ID : | 3247522 |
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 | 0.14 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 47.77 |
TPSA ? Topological Polar Surface Area: Calculated from |
49.69 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 |
1.43 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.03 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.6 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.1 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.39 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.13 |
Solubility | 1.37 mg/ml ; 0.00734 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.08 |
Solubility | 1.56 mg/ml ; 0.00834 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.03 |
Solubility | 1.73 mg/ml ; 0.00927 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 |
-6.42 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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.9 |
* 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 |
---|---|---|
Step 2 Preparation of 3-chloro-4-methoxyphenylboronic acid Following the general procedure outlined in Synthetic Scheme I, 10.2 g (46.2 mmol) of <strong>[50638-47-6]4-bromo-2-chloroanisole</strong> (Step 1) was converted to 3-chloro-4-methoxyphenylboronic acid: NMR (CDCl3) delta 3.83 (s, 3H), 6.57 (s, 2H), 6.83 (d, J=8 Hz, 1H), 7.64 (dd, J=1.5, 8 Hz, 1H), 7.77 (d, J=1.5 Hz, 1H). | ||
To a THF solution of <strong>[50638-47-6]4-bromo-2-chloroanisole</strong> was added an n-butyllithium/n-hexane solution at -78C, followed by 30 minutes of stirring. Then, trimethyl borate was added and the whole was warmed to room temperature, followed by 30 minutes of stirring. Using the residue obtained by evaporation of the solvent instead of 3,4-dimethoxyphenylboric acid, an objective compound was obtained in a similar manner to Reference Example 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: To a solution of compound 1a-e (10.0 mmol,1.0 eq) in anhydrousTHF (20 mL) was slowly added n-BuLi (6 mL of 2.5 M solution inhexane, 15.0 mmol, 1.5 eq) at 78 C. The mixture was stirred for1 h and triisopropyl borate (50.0 mmol, 5.0 eq) was added by syringe.The solutionwas stirred for another 1 h and allowed towarmto 25 C overnight. The reactionwas cooled to 0 C, followed by thesequential addition ofwater (5 mL) and 2N HCl (5 mL). After 10 min,an additional 35 mL of 2N HCl was added and the mixture wasfurther stirred for 30 min. The mixture was extracted with ethylacetate (20 mL * 3) and the combined organic layers wereconcentrated to a thick oil under reduced pressure. Crystallizationwith cold hexane yielded a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tripotassium phosphate tribasic; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct; In N,N-dimethyl-formamide; at 60℃; for 3h;Inert atmosphere; | A mixture of <strong>[6627-22-1]methyl 6-chloropyrimidine-4-carboxylate</strong> (200 mg, 1.16 mmol), (3-chloro-4-10 methoxy-phenyl)boronic acid (432 mg, 2.32 mmol), dichloro[1,1'- bis(diphenylphosphino)ferrocene]palladium dichloromethane adduct (85 mg, 0.12 mmol) and potassium phosphate (738 mg, 3.48 mmol) in DMF (10 mL) was purged with argon and heated in a sealed tube at 60 C for 3 h. After this time, the reaction mixture was concentrated under reduced pressure, and the residue obtained was purified by FCC (Silica, 0-5% MeOH in DCM) to give the title compound. m/z (ES+) (M+H)+ 279.0.1H NMR (300 MHz, DMSO-d6) δ 9.35 (d, J = 1.2 Hz, 1H), 8.53 5 (d, J = 1.2 Hz, 1H), 8.39 (d, J = 2.1 Hz, 1H), 8.31 (dd, J = 8.7, 2.4 Hz, 1H), 7.34 (d, J = 9.0 Hz, 1H), 3.97 (s, 3H), 3.95 (s, 3H). | |
With tripotassium phosphate tribasic; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II) dichloromethane adduct; In N,N-dimethyl-formamide; at 60℃; for 3h;Inert atmosphere; | A mixture of <strong>[6627-22-1]methyl 6-chloropyrimidine-4-carboxylate</strong> (200 mg, 1.16 mmol), (3-chloro-4-10 methoxy-phenyl)boronic acid (432 mg, 2.32 mmol), dichloro[1,1'- bis(diphenylphosphino)ferrocene]palladium dichloromethane adduct (85 mg, 0.12 mmol) and potassium phosphate (738 mg, 3.48 mmol) in DMF (10 mL) was purged with argon and heated in a sealed tube at 60 C for 3 h. After this time, the reaction mixture was concentrated under reduced pressure, and the residue obtained was purified by FCC (Silica, 0-5% MeOH in DCM) to give the title compound. m/z (ES+) (M+H)+ 279.0.1H NMR (300 MHz, DMSO-d6) δ 9.35 (d, J = 1.2 Hz, 1H), 8.53 5 (d, J = 1.2 Hz, 1H), 8.39 (d, J = 2.1 Hz, 1H), 8.31 (dd, J = 8.7, 2.4 Hz, 1H), 7.34 (d, J = 9.0 Hz, 1H), 3.97 (s, 3H), 3.95 (s, 3H). |
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