Structure of 603-84-9
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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. : | 603-84-9 |
Formula : | C6H4ClNO3 |
M.W : | 173.55 |
SMILES Code : | C1=C([N+]([O-])=O)C(=C(O)C=C1)Cl |
MDL No. : | MFCD11035882 |
InChI Key : | QBGLHYQUZJDZOO-UHFFFAOYSA-N |
Pubchem ID : | 3013917 |
GHS Pictogram: |
![]() ![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302-H315-H317-H318-H410 |
Precautionary Statements: | P261-P264-P270-P272-P273-P280-P301+P312+P330-P302+P352-P305+P351+P338+P310-P333+P313-P391-P501 |
Class: | 9 |
UN#: | 3077 |
Packing Group: | Ⅲ |
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 | 42.3 |
TPSA ? Topological Polar Surface Area: Calculated from |
66.05 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.2 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.07 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.95 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.88 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.13 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.19 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.56 |
Solubility | 0.48 mg/ml ; 0.00277 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.09 |
Solubility | 0.142 mg/ml ; 0.00082 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.81 |
Solubility | 2.66 mg/ml ; 0.0153 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 |
-5.89 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) |
1.8 |
* 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 |
---|---|---|
98% | With caesium carbonate; In DMF (N,N-dimethyl-formamide); at 18 - 22℃; | The nitrophenol starting material C2 (1.3 g; 7.49 MMOL) was dissolved in DMF (10 mL) and to this solution was added ground cesium carbonate (2.92 g; 8.96 MMOL), followed by Mel (1. 4 mL; 22. 5 MMOL). The mixture was stirred at room temperature overnight. The DMF was evaporated in vacuo and the residue taken up in ether (150 ML), washed with water (150 mL), brine (4x 100 mL), and then dried(MGSO4) THE organic phase was filtered and evaporated to afford the crude 2- CHLORO-3-NITROANISOLE C3 (98%; 1.38 g) as an orange solid. Homogeneity by HPLC (TFA) 220 nm: 93%. |
98% | With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; | Step B:; The nitrophenol starting material 1c1 (1.3 g; 7.49 mmol) was dissolved inDMF (10 ml) and to this solution was added ground cesium carbonate (2.92 g; 8.96mmol), followed by Mel (1.4 ml; 22.5 mmol). The mixture was stirred at roomtemperature overnight. The DMF was evaporated in vacuo and the residue taken upin ether (150 ml), washed with water (150 ml), brine (4 X 100 mL), and then driedover (MgSO4). The organic phase was filtered and evaporated to afford the crude 2-chloro-3-nitroanisole 1c2 (98%; 1.38 g) as an orange solid. |
98% | With caesium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; | The nitrophenol starting material 1c1 (1.3 g; 7.49 mmol) was dissolved in DMF (10 mL) and to this solution was added ground cesium carbonate (2.92 g; 8.96 mmol), followed by MeI (1.4 mL; 22.5 mmol). The mixture was stirred at room temperature overnight. The DMF was evaporated in vacuo and the residue taken up in ether (150 mL), washed with water (150 mL), brine (4×100 mL), and then dried(MgSO4). The organic phase was filtered and evaporated to afford the crude 2-chloro-3-nitroanisole 1c2 (98%; 1.38 g) as an orange solid. |
98% | With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; | The nitrophenol starting material 2c1 (1.3 g; 7.49 mmol) was dissolved inDMF (10 ml) and to this solution was added ground cesium carbonate (2.92 g; 8.96mmol), followed by Mel (1.4 ml; 22.5 mmol). The mixture was stirred at roomtemperature overnight. The DMF was evaporated in vacua and the residue taken upin ether (150 ml), washed with water (150 ml), brine (4 X 100 ml), and then driedover (MgSO4). The organic phase was filtered and evaporated to afford the crude 2-chloro-3-nitroanisole 2c2 (98%; 1.38 g) as an orange solid.Homogeneity by HPLC (TFA) (at) 220nm: 93%. |
With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; | 3-Nitrophenol (10 g, 72 mmol) was dissolved in hot concentrated hydrochloric acid (100 ml) and cooled rapidly (ice-brine bath) to give a fine suspension. Potassium chlorate (8.8 g, 72 mmol) was dissolved in water (100 ml) and added to the mixture and stirring continued at 0C for 2 hours. The reaction mixture was extracted with ethyl acetate (2X100 ml) and the combined organic extracts washed with water (100 ml), brine (100 ml), dried over sodium sulfate and evaporated in vacuo (water bath temp <45C) to give 2-chloro-3-nitrophenol (not purified) (Rf 0. 38,33% EtOAc/Pet spirit). The crude residue was dissolved in DMF and to this was added potassium carbonate (19.3 g, 140 mmol) and methyl iodide (5.6 ml, 90 mmol). The reaction mixture was stirred overnight at room temperature before diluting with ethyl acetate (200 ml) and washing with water (4X100 ml) and brine (100 ml). The organic phase was dried over sodium sulfate to give 2-chloro-3-nitroanisole (not purified) (Rf 0. 61. 33% EtOAc/Pet spirit). The crude residue obtained was dissolved in 2-aminoethylmorpholine 15.7 ml, 120 mmol) and butanol (50 ml) and heated at 100C for 16 hours under an atmosphere of nitrogen. Excess reagent and solvent were removed in vacuo and the residue diluted with EtOAc (200 ml) and 1M NaOH (100 ml). The organic phase was separated and the remaining aqueous solution extracted with EtOAc (2X100 ml). The organic extracts were combined and washed with brine (100 ml), dried over sodium sulfate, filtered and evaporated. The crude product was columned (silica) using a gradient from petroleum spirit to EtOAc (Rf 0.17, 50% EtOAc/Pet Spirit) to give 2-methoxy-N-(2-morpholinoethyl)-6- nitrobenzenamine (7.0 g, 35% yield over 3 steps). ESMS 282 (M+H). | |
With potassium carbonate; In acetone; at 70℃; for 4h; | (ii) 2-Chloro-3-nitrophenol (2.61 g, 15.04 mmol) and potassium carbonate (3.12 g, 22.56 mmol) were suspended in acetone (50 ml). Methyl iodide (1.034 ml, 16.54 mmol) was added and the mixture heated at 70 0C for 4 hours. The solids were filtered, washed with acetone and the filtrate concentrated to a solid. The crude product was purified by flash-silica gel chromatography, eluting with a 0-100% gradient of ethyl acetate in isohexane to afford 2-chloro-3-nitrophenyl methyl ether (2.44 g). |
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