Structure of 58755-57-0
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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. : | 58755-57-0 |
Formula : | C7H4ClNO3 |
M.W : | 185.56 |
SMILES Code : | ClC1=C(C=O)C=CC=C1[N+](=O)[O-] |
MDL No. : | MFCD08236804 |
Boiling Point : | No data available |
InChI Key : | WKIVBBWLRIFGHF-UHFFFAOYSA-N |
Pubchem ID : | 12667713 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 45.66 |
TPSA ? Topological Polar Surface Area: Calculated from |
62.89 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.04 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.88 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.06 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.86 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.48 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.26 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.41 |
Solubility | 0.717 mg/ml ; 0.00386 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.82 |
Solubility | 0.279 mg/ml ; 0.0015 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.34 |
Solubility | 0.84 mg/ml ; 0.00453 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 |
-6.1 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) |
1.65 |
* 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 |
---|---|---|
79.7% | With pyridinium chlorochromate; In dichloromethane; at 20℃; for 12h; | 8.43 g (39.09 mmol) of pyridinium chlorochromate (PCC) were added to a solution of 6.11 g (32.57 mmol) of <strong>[89639-98-5](2-chloro-3-nitrophenyl)methanol</strong> in 120 ml of dichloromethane, and the mixture was stirred at room temperature for 12 hours. After complete conversion, the solvent was evaporated to dryness under reduced pressure. The residue obtained was purified chromatographically on silica gel (mobile phase dichloromethane/methanol 20:1). This gave 4.82 g (25.97 mmol, 79.7% of theory) of the title compound.GC-MS (method 3): Rt=5.09 min; m/z=186 (M+H)+.1H-NMR (400 MHz, DMSO-d6): δ=10.35 (s, 1H), 8.33 (dd, 1H), 8.13 (dd, 1H), 7.77 (t, 1H). |
78% | A solution of oxalyl chloride in dichloromethane (2.0M, 116 mmol) was chilled to -70 C. (internal temperature) under a nitrogen atmosphere. DMSO (15 mL, 211.3 mmol) was added dropwise maintaining -65 C. and then stirring was continued for 45 min. at -70 C. A solution of the 3-nitro-2-chlorobenzyl alcohol (14.4 g, 76.6 mmol) in dichloromethane (250 mL) was then added and the reaction stirred at -70 C. for 2 h. Triethylamine (54 mL, 387 mmol) was added dropwise and the reaction stirred for 2 h at -70 C. and then 12 h at room temperature. The reaction was quenched by the addition of 500 mL of water. The aqueous phase was extracted twice with dichloromethane. The combined organic layers were washed with brine, dried with MgSO4, filtered, and evaporated to obtain a light brown solid. Column Chromatography (silica gel, 30% dichloromethane/hexanes to 70% dichloromethane/hexanes) produced 11.1 g (78%) of the desired 3-nitro-2-chlorobenzaldehyde as a yellow solid. 3-Nitro-2-chlorobenzaldehyde (11.1 g, 59.5 mmol) was dissolved in DMF (100 mL) and potassium carbonate (9.1 g, 66.2 mmol) was added. By slow addition, methyl thioglycoate (5.4 mL, 60.4 mmol) was added and a slight exotherm was observed. The reaction mixture was stirred 12 h at room temperature. Water (200 mL) was added to the reaction mixture which was then cooled on an ice/water bath. The solid was filtered and washed water until the filtrate was colorless, leaving the 13.3 g (94%) of the desired 7-nitro-benzo[b]thiophene-2-carboxylic acid methyl ester as a white solid. | |
74% | Step 2. 2-Chloro-3-nitrobenzaldehyde; A 250-mL 3-necked round-bottom flask was charged with a solution of oxalyl chloride (5.42 g, 42.70 mmol, 1.10 equiv) in DCM (100 mL). To this was added a solution of DMSO (6.65 g, 85.11 mmol, 2.20 equiv) in DCM (15 mL) drop wise -78 C. 2-Chloro-3-nitrophenyl)methanol (7.23 g, 38.54 mmol, 1.00 equiv) in DCM (35 mL) was added into the solution at -78 C. and allowed to stir for 1 hour. Then, TEA (30 mL) was added at this temperature and allowed to stir for an additional hour. Upon completion, the reaction was quenched with water and extracted with DCM (3×100 mL). Combined organic layers were dried over anhydrous sodium sulfate, filtered off and concentrated on a rotary evaporator. The residue was purified by a silica gel column chromatography eluted with PE:EA (10:1) affording 2-chloro-3-nitrobenzaldehyde as light yellow solid (5.3 g, 74%). |
With manganese(IV) oxide; In dichloromethane; at 20℃; | General procedure: MnO2 (508 g, 5.84 mol) was added to (2-bromo-4-nitro-phenyl)methanol (135.1 g, 0.582 mol) in DCM (1 L) and the reaction mixture was stirred overnight at rt. The mixture was filtered and the filtrate was evaporated to afford the title compound 18 (110.8 g, 83%) as a yellow solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With potassium fluoride; In N,N-dimethyl-formamide; at 150℃; for 5.0h; | To a solution of 2-chloro-3-nitrobenzaldehyde (9.5 g, 51.2 mmol) in DMF (100 mL) was added KF (8.9 g, 154 mmol). The reaction mixture was heated to 150 C and stirred at that temperature for 5 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The crude material was poured into H20 (400 mL) and extracted with DCM (100 mL x 4). The combined organic extracts were concentrated in vacuo and the crude material was purified by silica-gel column chromatography (petroleum ether/EtOAc, 20: 1) to give 2-fluoro-3- nitrobenzaldehyde as a yellow oil (6.7 g, yield: 77%). 1H NMR (400 MHz, CDCI3) d: 10.44 (s, 1H), 8.36-8.30 (m, 1H), 8.22-8.16 (m, 1H), 7.47 (t, J = 8.0 Hz, 1H). |