Structure of 138229-59-1
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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. : | 138229-59-1 |
Formula : | C9H7NO5 |
M.W : | 209.16 |
SMILES Code : | O=C(OC)C1=CC=CC(C=O)=C1[N+]([O-])=O |
MDL No. : | MFCD14706049 |
InChI Key : | NSLOBVGASZUPDO-UHFFFAOYSA-N |
Pubchem ID : | 44549250 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335-H412 |
Precautionary Statements: | P261-P273-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.11 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 51.93 |
TPSA ? Topological Polar Surface Area: Calculated from |
89.19 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.11 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.07 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.19 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.26 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.25 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.68 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.84 |
Solubility | 3.0 mg/ml ; 0.0144 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.53 |
Solubility | 0.611 mg/ml ; 0.00292 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.81 |
Solubility | 3.24 mg/ml ; 0.0155 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) |
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 |
-6.82 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) |
2.1 |
* 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 |
---|---|---|
78% | With 4-methylmorpholine N-oxide; In acetonitrile; at 20.0℃; for 2.0h;Molecular sieve; Inert atmosphere; | Compound 2 (2.74 g, 10 mmol) was weighed into a 150 mL single-necked flask, and a mixture (0.2 M) of molecular sieve in acetonitrile was added to dissolve it. Under the protection of nitrogen, N-methylmorpholine-N-oxide (2.34) was added. g, 20 mmol), reacted at room temperature for 2 hours, concentrated and poured into water, extracted three times with EA, the organic phase was washed with 1N HCl, brine, dried, filtered, concentrated, and subjected to column chromatography (eluent is petroleum ether : Ethyl acetate = 80: 1) to give Compound 3 (1.63 g, 78%) as a pale yellow solid. |
74% | With 4-methylmorpholine N-oxide; In acetonitrile; at 20.0℃; for 1.5h; | Step C; Methyl 3-Formyl-2-nitrobenzoate; Add N-methylmorpholine oxide (NMO, 6.10 g, 52.07 mmol) to a mixture of <strong>[132874-06-7]methyl 3-bromomethyl-2-nitrobenzoate</strong> (7.13 g, 26.023 mmol) and 4 A molecular sieves (35.32 g) in acetonitrile (150 mL) = at room temperature under nitrogen and stir for 1.5 h. Dilute the mixture with ethyl acetate (600 mL), filter the mixture by vacuum filtration and wash the filtrate with water (100 mL), 1 N HC1 (100 mL) and brine (150 mL) and dry over Na2S04. Remove the solvents under reduced pressure and purify the residue by flash column chromatography on silica gel, eluting with ethyl acetate/hexanes (1: 3), to provide methyl 3-formyl-2-nitrobenzoate as an off-white solid (4.04 g, 74%) : 1H NMR (CDC13) 8 3.95 (s, 3H), 7.77 (t, 1H), 8. 18 (dd, 1H), 8.28 (dd, 1H), 9. 98 (s, 1H). |
54% | With 4-methylmorpholine N-oxide; In acetonitrile; at 20.0℃; for 12.0h; | To a mixture of Compound F (1.97 g, 7.18 mmol) in MeCN (20 mL) was added N- methylmorpholine N-oxide (2.15 g, 17.9 mmol) at ambient temperature, and the reaction mixture was stirred for 12 h. The reaction mixture was diluted with EtOAc, washed with water, 1 M HCl and brine. The organic extracts were dried over Na2S04, filtered and evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel using 5% EtO Ac/petroleum ether to provide Compound G (824 mg, 3.93 mmol) in 54% yield. MR (400 MHz, CDCb) delta 9.96 (s, 1H), 8.26 (d, J= 7.9 Hz, 1H), 8.18 (d, J = 7.9 Hz, 1H), 7.77 (t, J= 7.9 Hz, 1H), 3.93 (s, 3H). MS (ES -) m/z: C9H7NO5 requires 209, found 208 (M - H)". Physical state: Off- white solid; R = 0.6 (mobile phase: EtOAc/hexanes, 1 :9). |
With 4-methylmorpholine N-oxide; In acetonitrile; at 20.0℃;Molecular sieve; | Step 3: Methyl 3-formyI-2-nitrobenzoate (A3); To a mixture of (A2) (1.0 eq.) and 4A mol. sieves in MeCN (0.2M) at RT was addedNMMO (2.0 eq.) and the reaction mixture was stirred for 1.5 hr under N2 atmosphere. Then, the mixture was diluted with EtOAc, filtered and the filtrate was washed with H2O, IN HCl, brine <n="37"/>and dried (Na2SO4). Evaporation of the solvent gave (A3) as a white solid which was used in the next step without further purification. 1H NMR (400MHz, CDCl3, 300K) delta 9.96 (IH, s), 8.26 (IH, d, J= 7.9 Hz), 8.18 (IH, d, J = 7.9 Hz), 7.77 (IH, t, J = 7.9 Hz), 3.93 (3H, s). MS (ES) C9H7NO5 requires: 209, found: 208 (M-H)'. | |
With 4-methylmorpholine N-oxide; In acetonitrile; at 20.0℃; for 1.5h;Molecular sieve; | Step 3: Methyl 3-formyl-2-nitrobenzoate (A3); To a mixture of (A2) and 4A mol. sieves (15 g) in MeCN (0.2M) at RT was added NMMO (2.0 eq.) and the reaction mixture was stirred for 1.5 hr under N2 atmosphere. Then, the mixture was diluted with EtOAc, filtered and the filtrate was washed with H2O, IN HCl, brine and dried (Na2SO4). Evaporation of the solvent gave (A3) as a white solid which was used in the next step without further purification. 1H NMR (400MHz, CDC13, 3OOK) delta 9.96 (IH, s), 8.26 (IH, d, J= 7.9 Hz), 8.18 (IH, d, J = 7.9 Hz), 7.77 (IH, t, J = 7.9 Hz), 3.93 (3H, s). MS (ES) C9H7NO5 requires: 209, found: 208 (M-H)". |
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