Structure of 859877-49-9
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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. : | 859877-49-9 |
Formula : | C7H7ClN2O3 |
M.W : | 202.60 |
SMILES Code : | NC1=C([N+]([O-])=O)C=C(Cl)C=C1OC |
MDL No. : | MFCD28405560 |
InChI Key : | MQNYHIKKJRBLTG-UHFFFAOYSA-N |
Pubchem ID : | 59644362 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 51.17 |
TPSA ? Topological Polar Surface Area: Calculated from |
81.07 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.48 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.22 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.85 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.65 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.37 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.16 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.7 |
Solubility | 0.4 mg/ml ; 0.00198 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.56 |
Solubility | 0.0561 mg/ml ; 0.000277 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.17 |
Solubility | 1.37 mg/ml ; 0.00678 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) |
Yes |
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 |
-5.96 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 |
3.0 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) |
2.37 |
* 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 N-chloro-succinimide; In acetonitrile; at 20 - 60℃; for 18h;Heating / reflux; | To a solution of the title compound of Example 21, Step A (26.6 mmol, 4.5 g) in MeCN (30 mL) at 60 C was added N-chlorosuccinimide (29 mmol, 3.9 g). The solution was brought to reflux for 2 h and allowed to stand at ambient temperature for 16 h. The reaction mixture was partitioned between CH2C12 and saturated NaHC03. The organic phase was washed with brine, dried with Na2SO4, and concentrated in vacuo to afford the product as a brown solid. LC-MS (ESI, Method B): 2.14 min, m/z 203.11 (M + 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.05 g (69%) | Step 2. 4-Chloro-2-methoxy-6-nitrophenylamine. Aniline 136 from the previous step (3.74 g, 22.2 mmol) was dissolved in acetonitrile (100 ml) and N-chlorosuccinimide (3.07 g, 23 mmol) was added. The mixture was heated under reflux overnight then concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to give product 137 as orange needles 3.05 g (69%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; sodium nitrite; In water; acetic acid; | Step 3. 1-chloro-3-methoxy-5-nitrobenzene. 4-Chloro-2-methoxy-6-nitroaniline (137) (14 g, 69 mmol) was dissolved in glacial acetic acid (115 ml) and treated with concentrated sulfuric acid (110 ml). The solution was cooled in an ice bath and a cold solution of sodium nitrite (5.03 g, 73 mmol) in water (20 ml) was added slowly to keep the reaction temperature below 5 C. After the addition was complete, the reaction was stirred for an additional 15 minutes before the addition of hypophosphorous acid (70 ml of a 50% solution in water, 0.9 M). The mixture was stirred at room temperature overnight and recooled with an ice bath. The solids were collected by filtration, washed with water, then dried under vacuum to give 3-chloro-5-nitro anisole (138) as a light salmon-colored solid 7.43 g, 57%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To the title compound of Example 21, Step B (19.9 mmol, 4.03 g) in DMF (50 mL) at 0 C was added portionwise NaH (31.8 mmol, 1.27 g of 60% suspension in mineral oil) (exothermic, gas evolution). After 10 min MeI (23 mmol, 1.5 mL) was added and the reaction was allowed to stand at ambient temperature for 3 h. Saturated NaHC03 and brine were added to the reaction resulting in formation of a precipitate, which was filtered, washed with water and dried in vacuo. Flash chromatography on silica eluting with 15% EtOAc in hexanes afforded the product as a bright red solid. LC-MS (ESI, Method B): 2.31 min, m/z 217.2 (M + 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With iron; ammonium chloride; In ethanol; water; for 4h;Reflux; | Step 3. 5-Chloro-3-meihoxybenzene-l,2-diamine. A mixture of 4-chloro-2- methoxy-6-nitroaniline (1.01 g, 5 mmol), Fe (1.68 g, 30 mmol), and NH4CI (2.67g, 50 mmol) in EtOH (10 mL) and water (5 mL) was stirred at reflux for 4hr and then filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography to give 5-chloro-3-methoxybenzene-l,2-diamine (0.80 g, 93% yield) as brown solid. LC-MS: m/z 173 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46.4% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 2h; | Step 2. 4-Chloro-2-methoxy-6-nitroaniline. To a mixture of 2-amino-5- chloro-3-nitrophenol (752 mg, 4.0 mmol) and potassium carbonate (415 mg, 3.0 mmol) in DMF was added Mel (625 mg, 4.4 mmol). The reaction mixture was stirred at r.t. for 2hr, then quenched with water and extracted with EtOAc. Combined organic layers were washed with brine, dried over anhydrous Na2S04 and concentrated under reduced pressure. The residue was purified by flash column chromatography to give 4-chloro-2- methoxy- 6-nitroaniline (450 mg, 46.4% yield). LC-MS: m/z 203(M-H)+. |
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