Structure of 2423-71-4
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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. : | 2423-71-4 |
Formula : | C8H9NO3 |
M.W : | 167.16 |
SMILES Code : | OC1=C(C)C=C([N+]([O-])=O)C=C1C |
MDL No. : | MFCD00007339 |
InChI Key : | FNORUNUDZNWQFF-UHFFFAOYSA-N |
Pubchem ID : | 17030 |
GHS Pictogram: |
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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 | 0.25 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 47.22 |
TPSA ? Topological Polar Surface Area: Calculated from |
66.05 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.5 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.18 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.92 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.94 |
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 |
1.13 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.92 |
Solubility | 1.99 mg/ml ; 0.0119 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.16 |
Solubility | 1.15 mg/ml ; 0.00687 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.97 |
Solubility | 1.79 mg/ml ; 0.0107 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 |
-6.48 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 |
2.0 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) |
1.56 |
* 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 |
---|---|---|
86% | With hydrogen;palladium 10% on activated carbon; In ethanol; under 1125.11 Torr; for 1h; | A solution of 1 g (6 mmol) of 2,6-dimethyl-4-nitrophenol in 20 ml of ethanol is placed under 1.5 bar of hydrogen in the presence of 10% Pd/C for 1 hour. The Pd/C is eliminated by filtration on celite and the filtrate is concentrated under reduced pressure. The evaporation residue crystallizes spontaneously, it is washed twice with 50 ml of heptane and dried overnight under vacuum. A cream coloured solid is obtained with a yield of 86%. [00525] Melting point: 139-140 C. |
85% | With hydrogen;palladium 10% on activated carbon; In methanol; at 20℃; under 2250.23 Torr; | Step 1: 4-amino-2,6-dimethyl-phenol; 3.00 g (18.0 mmol) 2,6-dimethyl-4-nitrophenol were hydrogenated with 0.50 g palladium on charcoal (Pd/C, 10%) in 50 mL MeOH in a 3 bar hydrogen atmosphere at RT. After the end of the reaction the catalyst was suction filtered and the filtrate was concentrated by rotary evaporation. The residue was triturated with DIPE and the precipitate was suction filtered and dried i. vac.Yield: 2.10 g (85% of theory)ESI-MS: m/z=138 (M+H)+ Rf: 0.5 (silica gel: DCM/MeOH/cyc/NH4OH=70:15:15:2) |
79% | With hydrogenchloride; tin; acetic acid; at 20℃; for 48h; | 4-Amino-2,6-dimethylphenol (15). Thesynthesis was carried out according to the methodology described in theliterature.5 2,6-Dimethyl-4-nitrophenol (0.60 g, 3.0 mmol), solidtin (1.14 g, 9.6 mmol), hydrochloric acid (0.72 mL), and acetic acid (7.2 mL)were placed in a round-bottomed flask. The system was kept under magneticstirring for 48 h at room temperature. Distilled water (60 mL) and aqueousNaHCO3 were added for neutralization and the product was extractedfrom the aqueous phase with ethyl acetate (100 mL). The organic phase waswashed with aqueous saturated NaHCO3, dried with MgSO4,filtered, and rotary-evaporated. The product was a red solid (0.33 g; 79% yield) withm.p. 107-109 C. IR (KBr, ν max/cm-1):3420, 3388 (N-H), 2949, 2919, 2853 (C-H), 1632, 1487 (C=C), 1234, 1205 (C-O,C-N). 1H NMR (200 MHz, CDCl3) δ/ppm: 7.13 (1H, s, OH), 6.15 (2H, s, Ar-H), 4.30 (2H, s,NH2), 2.01 (6H, s, 2×CH3). |
With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; for 4h; | A suspension of 50 g of 4-nitro-2,6-dimethylphenol (MW=167.16; 294.5 mmol) and 5 g of 10% palladium-on-charcoal (MW=106.41; 4.7 mmol) in 1000 ml of ethanol was stirred at room temperature under a hydrogen atmosphere in a Parr hydrogenator for 4 hours. The mixture was then filtered under nitrogen through a layer of Celite and the solvent was evaporated off under reduced pressure.The solid residue thus obtained was 4-amino-2,6-dimethylphenol (38 g), which was used in subsequent reactions without further purification.LC/MS (M+H)+=138; 123 (base peak).1H-NMR (δ, DMSO d-6) 7.5-6.8 (broad s, 1H); 6.16 (s, 2H); 4.5-3.9 (broad s, 2H); 2.03 (s, 6H). | |
With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; for 4h; | A suspension of 50 g of 4-nitro-2,6-dimethylphenol (MW = 167.16; 294.5 mmol) and 5 g of 10% palladium-on-charcoal (MW = 106.41 ; 4.7 mmol) in 1000 ml of ethanol was stirred at room temperature under a hydrogen atmosphere in a Parr hydrogenator for 4 hours. The mixture was then filtered under nitrogen through a layer of Celite and the solvent was evaporated off under reduced pressure.The solid residue thus obtained was 4-amino-2,6-dimethylphenol (38 g), which was used in subsequent reactions without further purification.LC/MS (M+H)+ = 138; 123 (base peak).1H-NMR (δ, DMSO d-6) 7.5-6.8 (broad s, 1 H); 6.16 (s, 2H); 4.5-3.9 (broad s, 2H); 2.03 (s, 6H). |
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