Structure of 6952-67-6
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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. : | 6952-67-6 |
Formula : | C9H9NO4 |
M.W : | 195.17 |
SMILES Code : | O=[N+](C1=CC(C2OCCO2)=CC=C1)[O-] |
MDL No. : | MFCD00020899 |
InChI Key : | YOGPCAYIEHLIMG-UHFFFAOYSA-N |
Pubchem ID : | 240610 |
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 | 0.33 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 49.9 |
TPSA ? Topological Polar Surface Area: Calculated from |
64.28 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.85 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.16 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.32 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.26 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
-0.01 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.11 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.97 |
Solubility | 2.11 mg/ml ; 0.0108 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.1 |
Solubility | 1.53 mg/ml ; 0.00786 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-1.86 |
Solubility | 2.68 mg/ml ; 0.0137 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 |
-6.67 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) |
2.14 |
* 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 |
---|---|---|
97% | With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃; for 4h; | A mixture of compound 3 (1.95 g, 0.01 mol) and Pd/C (0.1 g,10%) in 50 mL methanol was stirred under hydrogen at room temperaturefor 4 h. The reaction mixture was filtered and the filtratewas evaporated to afford compound 4, a yellow oil with 97% yield,MS (ESI) m/z: 166 (M+ H)+. The 1H NMR spectrum was in accordancewith that described in the literature.42 |
82.7% | With iron; ammonium chloride; In ethanol; water; at 80℃; for 0.5h; | Compound 16b (6.45 g, 33.1 mmol) was dissolved in a mixed solvent of ethanol (50 mL) and water (25 mL) at room temperature.Ammonium chloride (885.4 mg, 16.55 mmol) and iron powder (9.27 g, 165.5 mmol) were added and reacted at 80 C for about 30 minutes.After the TLC was used to detect the completion of the reaction, the mixture was filtered while hot, and the filtrate was evaporated under reduced pressure.The organic phase was combined, washed with brine, dried over anhydrous magnesium sulfateThe yellow liquid compound 16c was obtained in an amount of 4.52 g, yield 82.7%. |
55% | With palladium on activated charcoal; hydrogen; In ethanol; at 20℃; | Step 10b. 3-(1,3-Dioxolan-2-yl)aniline (compound 8003) A mixture of 8002 (215 mg, 1.1 mmol), Pd/C (100 mg, 50%) in ethanol (10 mL) was stirred under hydrogen at room temperature overnight. The mixture was filtered and the filtrate was evaporated in vacuo. The crude product was purified by column chromatography (hexanes/ethyl acetate: 8/1) to afford compound 8003 as a yellow solid (100 mg, 55%). LCMS: m/z 166.1 [M+1]+. 1H NMR (400 MHz, DMSO-d6): δ 3.86-4.03 (m, 4H), 5.10 (s, 1H), 5.55 (s, 1H), 6.54 (d, J=7.6 Hz, 2H), 6.63 (s, 1H), 6.99 (t, J=7.6 Hz, 1H). |
With hydrogen;palladium on activated charcoal; In ethanol; for 4h; | For compound (163) the commercially 3-nitrobenzaldehyde was converted to the cyclic acetal, 2-(3-nitro-phenyl)-[1,3]dioxolane using ethylene glycol and TsOH in refluxing benzene under Dean-Stark conditions. The nitro group of the 1.0 dioxolane was then reduced via H2 Pd/C reduction in EtOH (See above compound 42) for 4 hrs to give the phenylamine, 3-[1,3]dioxolan-2-yl-phenylamine. The phenylamine was alkylated with 2 eq 3-chloro-1,2-propanediol in EtOH using K2CO3 at RT (See above compound 41) for 48 hr. (to give 3-[(2,3-dihydroxy-propyl)-(3-[1,3]dioxolan-2-yl-phenyl)-amino]-propane-1,2-diol. The cyclic acetal of this dioxolane deprotected using 1 M HCl in THF for 20 min to give 3-[bis-(2,3-dihydroxy-propyl)-amino]-benzaldehyde. This aldehyde was coupled with the respective hydrazine to give the hydrazone under conditions given in Example 5; | |
With hydrazine hydrate; In methanol; for 1h;Reflux; | A mixture of the nitro compound 3 (6.5 mmol), hydrazine hydrate(18.5 mmol) and Raney nickel (356 mg) in methanol (25.0 mL)was heated under reflux for 1 h. The hot solution was filtered andevaporated under reduced pressure. After cooling, the oil wasfiltered through a pad of silica gel for purification.4.2.2.1. 3-(1,3-Dioxolan-2-yl)aniline 4. Yellow oil; 89% yield. FTIR (ATR) ν (cm-1): 3365 and 3226 (NH2), 1625 (C=C), 1316(=C-N), 1092 and 1070 (C-O-C). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.86-4.02 (m, 4H, H4', H5'), 5.09 (s, 2H, NH2), 5.56 (s, 1H, H20),6.53-6.59 (m, 2H, H4, H6), 6.66 (d, J = 1.7 Hz, 1H, H2), 7.01 (t,J = 7.7 Hz, 1H, H5). MS (70 eV) m/z (%): 165/166 [M+] (100/11), 164(49), 120 (26), 93 (40), 73 (23). | |
With iron; ammonium chloride; In ethanol; water; at 80℃; for 1h; | General procedure: A slurry of nitro-compound (1.0 equiv.), iron powder (5.0 equiv.)and ammonium chloride (0.5 equiv.) in EtOH/H2O (3:1) was heated at 80 C for 1 h. The mixture was filtered through celite. The filtrate was extracted with EA. The combined organic layers were washed with brine, dried over anhydrous Na2SO4. The solvent was evaporated and the crude product was charged on a silica gel column chromatographyto afford amine in high yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With toluene-4-sulfonic acid; In ethylene glycol; benzene; | A mixture of 3-nitrobenzaldehyde (100 g, 0.66 mole), ethylene glycol (49.3 g, 0.7 mole) and p-toluenesulfonic acid (0.8 g) and benzene (1 L) was heated at reflux with continuous removal of water via a Dean and Stark trap. After 4 hours, the mixture was cooled, filtered through a pad of neutral alumina and concentrated in vacuo to afford 2-(3-nitrophenyl)-1,3-dioxolane (130.4 g, 100%) as an amber oil used without further purification below. Step (b) 2-(3-Aminophenyl)-1,3-dioxolane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium chloride; In water; | Preparation 118 To a mixture of 2-(3-nitrophenyl)-1,3-dioxolane (12.8g), ammonium chloride (1.75g), ethyl alcohol (100ml) and water (50ml) were added Celite (12.8g) and iron powder (11.0g) under stirring at 70C. The stirring was continued at reflux for 40 minutes. After cooling, the reaction mixture was diluted with ethyl acetate (250ml) and filtered through Celite. The filtrate was washed with saturated aqueous sodium hydrogen carbonate (200ml) and brine (100ml). The separated organic layer was dried over magnesium sulfate, decolored with activated carbon and filtered. The solvent was evaporated to give 3-(1,3-dioxolan-2-yl)aniline (9.76g) as oil. MS:166(M+1) NMR(DMSO, δ):3.8-4.1(4H,m). 5.10(2H,br s), 5.55(1H,s), 6.4-6.7(3H,m), 7.00(1H,t, J=7.7Hz) |
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