Structure of 185345-46-4
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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. : | 185345-46-4 |
Formula : | C7H4BrFO2 |
M.W : | 219.01 |
SMILES Code : | O=CC1=CC(F)=C(O)C(Br)=C1 |
MDL No. : | MFCD21606586 |
InChI Key : | FSLFKQZWBRMALB-UHFFFAOYSA-N |
Pubchem ID : | 18701750 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 41.51 |
TPSA ? Topological Polar Surface Area: Calculated from |
37.3 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.39 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.82 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.53 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.97 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.6 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.06 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.68 |
Solubility | 0.455 mg/ml ; 0.00208 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.22 |
Solubility | 1.31 mg/ml ; 0.00598 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.91 |
Solubility | 0.269 mg/ml ; 0.00123 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) |
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 |
-6.34 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) |
1.38 |
* 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 |
---|---|---|
48% | With bromine; acetic acid; at 45.0℃; for 26.0h; | Intermediate 26. 3-bromo-5-fluoro-4-hydroxybenzaldehyde (26)26; [0198] To a solution of 3-fluoro-4-hydroxybenzaldehyde (2 g, 14.3 mmol, 1 eq, Oakwood Products, Inc., West Columbia, SC, USA) in acetic acid (60 mL), was added a solution of bromine(2.7 g, 17.0 mmol, 1.2 eq) in acetic acid(10 mL), and the mixture was stirred at 45 C for 26 h. After concentration in vacuo, brine (50 mL) was added to the residue and the mixture was extracted with EtOAc(3 X 80 mL). The combined organic layers were dried (Na2SO4), concentrated in vacuo, and purified by reversed phase semi-preparative .HPLC to afford 1.5 g (48%) of_3-bromo-5-fluoro-4- hydroxybenzaldehyde (26). |
48% | With bromine; In acetic acid; at 45.0℃; for 26.0h; | Intermediate 12: 3-bromo-5-fluoro-4-hydroxybenzaldehyde (12)12[0157] To a solution of 3-fluoro-4-hydroxybenzaldehyde (2 g, 14.3 mmol, 1 eq) in acetic acid (60 mL), was added a solution of bromine(2.7 g, 17.0 mmol, 1.2 eq) in acetic acid(10 mL), and the mixture was stirred at 45 C for 26h. After concentration in vacuo, brine (50 mL) was added to the residue and the mixture was extracted with EtOAc(3 X 80 mL). The combined organic layers were dried (Na2SO4), concentrated in vacuo, and purified by reversed phase semi-preparative .HPLC to afford 1.5 g (48 %) of_3-bromo-5-fluoro-4-hydroxybenzaldehyde (12). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | With hydrogenchloride; In ethanol; water; at 95.0℃; for 50.0h;Inert atmosphere; | [00305] Step 1: Synthesis of 4-(3-bromo-5-fluoro-4-hydroxyphenyl)-5,6-diphenyl- 3,4-dihydropyrimidin-2(lH)-one: To a mixture of 3-bromo-5-fluoro-4- hydroxybenzaldehyde (Intermediate 77) (600 mg, 2.7 mmol), 1,2-diphenylethanone (538 mg, 2.7 mmol), urea (493 mg, 8.2 mmol) and cone HC1 (1 mL) in ethanol (4 mL) was heated at 95C for 50 hours. The mixture was evaporated under reduced pressure and was purified by silica gel column chromatography (petroleum ether/ethyl acetate =2: 1) to give product (400 mg, yield 33%) as yellow solid. 1H NMR (DMSO 300MHz) : deltaIotaOmicronLambdaIota (brs, 1H), 8.66 (s, 1H), 7.45 (s, 1H), 7.24-6.95 (m, 10H), 6.75 (d, J = 7.8 Hz, 2H), 5.07 (s, 1H). [00306] |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With oxygen; cobalt(II) diacetate tetrahydrate; sodium hydroxide; In ethylene glycol; at 80.0℃; under 760.051 Torr; for 8.0h; | General procedure: a mixture of substrate 1a(1 mmol), cobalt salt (n1mol%) and NaOH (n2 equiv)in EG (5 mL) was stirred with O2 (1 atm) being bubbled, under 80 oCfor 8 h. Hydrochloric acid (10 mL, 2%) and methyl tert-butyl ether (MTBE, 10 mL) were successively added to the reactionmixture. The organic layer was separated, and the aqueous phase was furtherextracted with MTBE(10 mL × 2). The combined organic phase was dried over anhydrous sodium sulfateand concentrated to give a residue, which was purified by column chromatographyon silica gel (eluents: petroleum ether/ethyl acetate, 10/1) to provide thedesired products 2a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With piperidine; In ethanol; at 80.0℃; for 16.0h;Inert atmosphere; | General procedure: Piperidine (8.7 muL, 0.088 mmol), 3,5-difluoro-4-hydroxybenzaldehyde (69.5 mg, 0.44 mmol) and S3 (100.0 mg, 0.44 mmol) were dissolved in EtOH (2.0 mL). The mixture was heated to 80 oC for 16 h. The orange solid was filtered and washed with 1N HCl and Et2O to afford 3 (114.0 mg, 70%, mixture of E/Z isomers). |
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