Structure of 59483-54-4
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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. : | 59483-54-4 |
Formula : | C6H5ClN2O2 |
M.W : | 172.57 |
SMILES Code : | C1=CC=C(C(=C1N)[N+](=O)[O-])Cl |
MDL No. : | MFCD01317803 |
InChI Key : | YADOEPHJIBKBCN-UHFFFAOYSA-N |
Pubchem ID : | 101068 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H312-H332 |
Precautionary Statements: | P280 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 44.68 |
TPSA ? Topological Polar Surface Area: Calculated from |
71.84 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.19 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.25 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.84 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.88 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.37 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.16 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.67 |
Solubility | 0.373 mg/ml ; 0.00216 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.39 |
Solubility | 0.0696 mg/ml ; 0.000403 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.03 |
Solubility | 1.61 mg/ml ; 0.00931 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 |
-5.76 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 |
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) |
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 |
---|---|---|
72% | With N-Bromosuccinimide; In acetic acid; for 0.75h;Reflux; | 5.00 g (28.973 mmol) of 3-chloro-2-nitroaniline and 5.05 g (28.394 mmol) of N-bromosuccinimide were dissolved in 250 ml acetic acid. The mixture was boiled under reflux for 45 min. After cooling, the reaction mixture was added to 1.5 1 water. The resultant precipitate was filtered off and dried under high vacuum. We obtained 5.25 g (72% of theor.) of the target compound.LC-MS (method 9): R, = 2.16 min; MS (Elmin): m/z = 251 [M-H]+. 1H-NMR (400 MHz, DMSO-D6): δ [ppm] = 6.40 (sbr, 2H), 6.83 (d, IH), 7.56 (d, IH). |
68.6% | With N-Bromosuccinimide; acetic acid; for 0.75h;Reflux; | 4-Bromo-3-chloro-2-nitroaniline3-Chloro-2-nitroaniline (10 g, 57.9 mmol) and NBS (10.31 g, 57.9 mmol) were dissolved in AcOH (500 mL). The reaction mixture was stirred at reflux temperature for 45 min. After cooling, the reaction mixture was added to 1.5L of water. The resultant precipitate was filtered off and dried under high vacuum to give 10 g (68.6%) of the title compound. |
67% | With N-Bromosuccinimide; acetic acid; for 1h;Reflux; | Intermediate 12A; 4-bromo-3-chloro-2-nitroaniline; 3-Chloro-2-nitroaniline (5.00 g, 29.0 mmol) was dissolved in glacial acetic acid (258 mL). N-Bromosuccinimide (5.06 g, 28.4 mmol) was added and the resulting mixture was refluxed for 1 hour. The reaction was cooled to room temperature and poured into water to give a precipitate that was filtered, rinsed with water and dried to constant weight to give the title compound (4.78 g, 67%o). .H NMR (400 MHz, CDCL3) δ ppm 7.46 (d, J= 9.0, 1H), 6.64 (d, J= 9.0, 1H), 4.74 (s, 2H). |
62% | With N-Bromosuccinimide; acetic acid;Inert atmosphere; Reflux; | A solution of 3-chloro-2-nitroaniline (25.0 g 0.145 mol) and NBS (25.8 g 0.145 mol) in acetic acid (1 L) was heated at reflux under N2 overnight. Water (1 L) was added and the insoluble matter was collected by filtration to give the title compound (22.3 g, 62%) as a gray solid. LCMS-C (ES-API): rt 3.84 min; m/z 250.9, 252.9 [M+H]+. 1 H NMR (400 MHz, DMSO-de) d 7.56 (d, J = 9.2 Hz, 1 H), 6.84 (d, J = 9.2 Hz, 1 H), 6.41 (s, 2H). |
23% | With N-Bromosuccinimide; acetic acid; at 80℃; for 1.5h; | In a 2 L three necked flask, a solution of 3-chloro-2-nitroaniline (60 g, 348 mmol) in AcOH (600 mL) was treated portionwise with NBS (61.9 g, 348 mmol). The resultant orange solution was heated at 80 C for 1.5 h. The reaction mixture was cooled to RT and was poured into stirred ice water (800 mL). The resultant orange precipitate was collected by filtration, washed with water (200 mL). The orange residue was collected and dissolved in EtOAc (500 mL). The solution was dried with MgSO4, filtered and the solvent was concentrated in vacuo to give an orange solid (86.5 g). The residue was recrystallised from 10% EtOAc/iso-Hexane (500 mL). The resultant solid was filtered, rinsing with iso-Hexane (100 mL), and dried in vacuo to afford a light orange solid (39.88 g, 158.6 mmol, 46%). The filtrate was concentrated in vacuo to give an orange solid. The residue was recrystallised from 10% Ac/iso-Hexane (250 mL). The resultant solid was filtered, rinsing with iso-Hexane (50 mL), and dried in vacuo to afford a light orange solid (20 g, 79.53 mmol, 23%).1H NMR in DMSO-d6: (7.55 (1H, d), 6.84 (1H, d), 6.40 (2H, s). Step |
13g | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0 - 20℃;Inert atmosphere; | A solution of BS (10.31 g ) in DMF (25 mL) was added to a solution of 3- chloro-2-nitroaniline in DMF (100 mL) at 0 C. The resulting solution was stirred at 0 C for 1 hour then allowed to warm to room temperature and stirred at room temperature overnight. The orange solution was taken up in EtOAc and washed 3 times with water. Then the organic layer was dried (Na2S04) and the solvent was removed under reduced pressure. The residue was rinsed with hexanes and collected via filtration to provide 13 g of the title compound as a brown solid. |
13 g | With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0 - 20℃; | [0658] A solution ofNBS (10.31 g ) in DMF (25 mL) was added to a solution of 3-chloro- 2-nitroaniline in DMF (100 mL) at 0 C. The resulting solution was stirred at 0 C for 1 h, then allowed to warm to room temperature and stirred overnight. The orange solution was taken up in EtOAc and washed 3 times with water. Then the organic layer was dried (Na2SO4) and the solvent was removed under reduced pressure. The residue was rinsed with hexanes and collected via filtration to provide 13 g of brown solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In methanol; water; at 0 - 20℃; for 3h; | To a mixture of X4-013-6 (1 g, 3.5 mmol) and 3-methylpicolinaldehyde (639 mg, 5.28 mmol) in MeOH (40 ml) was added a solution of NaOH (210 mg, 5.28 mmol) in H20 (2 mL) at 0 °C and the mixture was stirred at room temperature for 3 h. The pH was adjusted to 8 with 35percent HC1 aq., dried over anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by column chromatography to give X4-357-1 (1.15 g, 84.4 percent yield) as yellow solid. LCMS (Agilent LCMS 1200-6120, Column: Waters X-Bridge C18 (50 mm*4.6 mm*3.5 iim); Column Temperature: 40 °C; Flow Rate: 2.0 mL/min; Mobile Phase: from 90percent [(total 10mM AcONH4) water/CH3CN = 900/100 (v/v)] and 10percent [(total 10mM AcONH4) water/CH3CN = 100/900 (v/v)] to 10percent [(total 10mM AcONH4) water/CH3CN = 900/100 (v/v)] and 90percent [(total 10mM AcONH4) water/CH3CN = 100/900 (v/v)] in 1.6 mm, then under this condition for 2.4 mm, finally changed to 90percent [(total 10mM AcONH4) water/CH3CN = 900/100(v/v)] and 10percent [(total 10mM AcONH4) water/CH3CN = 100/900 (v/v)] in 0.1 mm and under thiscondition for 0.7 mm). Purity: 89.3 percent. Rt = 1.48 mm; MS Calcd.: 387.2; MS Found: 388.3 [M +H]t |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-Bromosuccinimide; acetic acid; for 0.75h;Reflux; | A solution of 3-chloro-2-nitroaniline (25 g, 145 mmol) and N-bromosuccinimide (25.5 g, 143 mmol) inAcOH (600 mL) was refluxed for 45 mm. After cooling to RT, the reaction mixture was poured into ice-cold water (2 L). The precipitate was collected by filtration, washed with ice-cold water (2 x200 mL) anddried in a vacuum oven overnight, to give the title compounds (36 g) as a mixture of isomers (4-bromo/6-bromo in 9:1 ratio). 1H NMR (500 MHz, DMSO-d6): 7.56 (1H, d), 6.84 (1H, d), 6.40 (2H, 5). | |
With N-Bromosuccinimide; acetic acid; for 0.75h;Reflux; | A solution of 3-chloro-2-nitroaniline (25 g, 145 mmol) and N-bromosuccinimide (25.5 g, 143 mmol) in AcOH (600 mL) was refluxed for 45 min. After cooling to RT, the reaction mixture was poured into ice-cold water (2 L). The precipitate was collected by filtration, washed with ice-cold water (2 x 200 mL) and dried in a vacuum oven overnight, to give the title compounds (36 g) as a mixture of isomers (4-bromo/6-bromo in 9:1 ratio). 1H NMR (500 MHz, DMSO-d 6) δ: 7.56 (1H, d), 6.84 (1H, d), 6.40 (2H, s). |
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