Structure of 53553-14-3
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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. : | 53553-14-3 |
Formula : | C8H6ClNO4 |
M.W : | 215.59 |
SMILES Code : | O=C(OC)C1=CC=CC([N+]([O-])=O)=C1Cl |
MDL No. : | MFCD00482383 |
InChI Key : | JBCQPBVZKBEHNF-UHFFFAOYSA-N |
Pubchem ID : | 10751184 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 51.55 |
TPSA ? Topological Polar Surface Area: Calculated from |
72.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.55 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.29 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.03 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.43 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.22 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.5 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.74 |
Solubility | 0.394 mg/ml ; 0.00183 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.44 |
Solubility | 0.0779 mg/ml ; 0.000361 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.48 |
Solubility | 0.717 mg/ml ; 0.00333 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) |
Yes |
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 |
-5.99 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 |
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) |
1.93 |
* 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 |
---|---|---|
8.6 g (100%) | In ethyl acetate; | b) Methyl 2-chloro-3-aminobenzoate Hydrogen gas was passed through a solution of methyl 2-chloro-3-nitrobenzoate (10.0 g, 46.4 mM) and 1.0 g of 3% sulfided platinum on carbon in 150 mL ethyl acetate for 48 hours at room temperature. The catalyst was removed by filtration through celite. Concentration of the filtrate afforded 8.6 g (100%) of methyl 2-chloro-3-aminobenzoate as a yellow oil. 1H NMR (CDCl3) delta 7.25 (dd, 1H, J=1 and 8 Hz), 7.2 (t, 1H, J=8 Hz), 6.95 (dd, 1H, J=1 and 8 Hz), and 3.9 (s, 3H). IR (CHCl3, cm-1) 3450, 3380, 2980, 2900, 1729, 1615, 1456, 1434, 1322, 1290, and 1268. MS (ES) m/e 186, 188. Elemental Analyses for C8H8NO2Cl: Calculated: C, 51.77; H, 4.34; N, 7.55. Found: C, 51.52; H, 4.17; N, 7.54. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With ammonium chloride; zinc; In methanol; at 20 - 60℃; for 3h; | To the solution of 213A: (1 g, 4.64 mmol) in MeOH(23.19 ml) was added ammonium chloride (2.481 g, 46.4 mmol) and zinc dust (1.516 g, 23.19 mmol). The reaction was stirred at rt for 2 h, then warmed to 60C for 1 h. The reaction was filtered through a pad of Celite, rinsing withMeOH. The filtrate was concentrated. The residue was partitioned between EtOAc and water and the layers were separated. The organiclayer washed with sat. NaHCO3, brine, dried over Na2SO4, filtered, and concentrated. Purification by silica gel chromatography afforded 213B (0.85 g,99 % yield) as a yellow oil. |
98% | With hydrogenchloride; iron; In ethanol; water;Reflux; | Procedure: The ester (1.06 g, 4.9 mmol, 1 eq.) and HCIaq(1 m, 4.9 ml_, 1 eq.) were dissolved in EtOH (0.25 m) and heated to reflux. Fine powdered iron (302 mg, 5.4 mmol, 1 .1 eq.) was added in portions to the hot solution and the resulting mixture was refluxed until complete consumption of the starting material. The crude mixture was passed through a Celite pad, diluted with EtOAc and the organic layer was washed with water and brine. The combined organic layers were dried over Na2S04, the solvent was removed under reduced pressure and the product was used without further purification.Yield: 1 .06 g, 4.8 mmol, 98% (brown oil).TLC: PE/EtOAc 25% |
83.5% | With hydrogen; In methanol; at 25℃; under 2585.81 Torr; for 3.5h;Inert atmosphere; | To a solution of methyl 2-chloro-3-nitrobenzoate (25 g, 1 16 mmol) in MeOH (150 ml_) was added Raney Ni (3 g). The mixture was stirred under H2 atmosphere (50 psi at 25 C) for 3.5 h. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the crude product, which was purified by recrystallization in EtOAc to afford the title compound. 69 g (83.5% yield, four batches combined) 1H NMR (400 MHz, CDCIs) delta ppm 6.70-7.25 (m, 3H), 4.40-4.50 (br, 2H), 3.87 (s, 3H). |
83.5% | With hydrogen;nickel; In methanol; at 25℃; under 2585.81 Torr; for 3.5h; | Step B: Methyl 3-amino-2-chlorobenzoate; To a solution of methyl 2-chloro-3-nitrobenzoate (25 g, 116 mmol) in MeOH (150 mL) was added Raney Ni (3 g). The mixture was stirred under H2 atmosphere (50 psi at 25 C.) for 3.5 h. The catalyst was filtered, and the filtrate was concentrated under the reduced pressure to dryness to give the crude product, which was purified by recrystallization in EtOAc to afford the title compound (69 g, 83.5% yield, four batches combined). 1H NMR (400 MHz, CDCl3) delta ppm 6.70-7.25 (m, 3H), 4.40-4.50 (br, 2H), 3.87 (s, 3H). |
2.6 g (50%) | With sodium hydroxide; stannous chloride; In hydrogenchloride; ethanol; | b) Methyl 2-chloro-3-aminobenzoate A solution of stannous chloride (27.0 g, 137.0 mM) in 55 mL of concentrated hydrochloric acid was slowly added to a solution of methyl 2-chloro-3-nitrobenzoate (6.0 g, 27.9 mM) in 75 mL ethanol at 15-20 C. over 1 hour. The mixture was then heated at 50-60 C. for 15 minutes. The mixture was cooled to room temperature and made alkaline by slow addition of solid sodium hydroxide maintaining a temperature of 30-35 C. The resultant mixture was extracted three times with chloroform. The extracts were washed with brine, dried over sodium sulfate, filtered and concentrated to afford 2.6 g (50%) of methyl 2-chloro-3-aminobenzoate as a yellow oil, identical in all respects to the material derived via catalytic hydrogenation described above. |
1.2 g (33%) | With sodium carbonate; In tetrahydrofuran; methanol; water; | b) Methyl 2-chloro-3-aminobenzoate A solution of sodium dithionite (14.0 g, 20.0 mM) and sodium carbonate (6.7 g) in 200 mL of water was slowly added to a solution of methyl 2-chloro-3-nitrobenzoate (6.0 g, 27.9 mM) in 40 mL methanol and 40 mL of tetrahydrofuran at 25 C. over 30 minutes. The mixture was stirred at room temperature for an additional 30 minutes, then extracted with ethyl acetate. The extracts were washed with brine, dried over sodium sulfate, filtered and concentrated to afford 1.2 g (33%) of methyl 2-chloro-3-aminobenzoate as a yellow oil, identical in all respects to the material derived via catalytic hydrogenation described above. |
With ammonium formate; acetic acid; zinc; In tetrahydrofuran; methanol; at 20℃; for 18h; | Step A: methyl 3-amino-2-chlorobenzoate: To a solution of methyl 2-chloro-3-nitrobenzoate (2.1 g, 9.7 mmol) in methanol (100 mL) and THF (20 mL) was added zinc powder (1.9 g, 29 mmol), ammonium formate (3.1 g, 49 mmol), and a few drops of acetic acid. The mixture was allowed to stir at RT for 18 hours. Most of the volatiles were removed under reduced pressure. The residue was redissolved in EtOAc (200 mL), washed with brine, concentrated and purified by MPLC to provide methyl 3-amino-2-chlorobenzoate. | |
With ammonium formate; acetic acid; zinc; In tetrahydrofuran; methanol; at 20℃; for 18h; | Step A: methyl 3-amino-2-chlorobenzoate: To a solution of methyl 2-chloro-3-nitrobenzoate (2.1 g, 9.7 mmol) in methanol (100 mL) and THF (20 mL) was added zinc powder (1.9 g, 29 mmol), ammonium formate (3.1 g, 49 mmol), and a few drops of acetic acid. The mixture was allowed to stir at RT for 18 hours. Most of the volatiles were removed under reduced pressure. The residue was redissolved in EtOAc (200 mL), washed with brine, concentrated and purified by MPLC to provide methyl 3-amino-2-chlorobenzoate. | |
19 g | With iron; ammonium chloride; In methanol; water; at 80℃; for 2h; | To a solution of methyl 2-chloro-3-nitrobenzoate (23.0 g, 107 mmol) in MeOH (100 mL) and H2O (20 mL) were added Fe (29.8 g, 533 mmol) and NH4Cl (45.7 g, 853 mmol). The mixture was stirred at 80 C for 2 hours. The mixture was filtered out and the filtrate was concentrated to give a residue. The residue was purified by silica gel chromatography to give methyl 3-amino-2- chlorobenzoate (I-484) (19.0 g) as a yellow oil. |
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