Structure of 127221-02-7
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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. : | 127221-02-7 |
Formula : | C14H15NO4 |
M.W : | 261.27 |
SMILES Code : | O=C(C(N1)=CC2=C1C=CC(C(OCC)=O)=C2)OCC |
MDL No. : | MFCD03094964 |
InChI Key : | IEFLIZMMNNHRSB-UHFFFAOYSA-N |
Pubchem ID : | 15629756 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 19 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.29 |
Num. rotatable bonds | 6 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 70.47 |
TPSA ? Topological Polar Surface Area: Calculated from |
68.39 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.87 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.82 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.52 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.81 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.03 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.61 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.19 |
Solubility | 0.168 mg/ml ; 0.000644 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.91 |
Solubility | 0.0319 mg/ml ; 0.000122 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.25 |
Solubility | 0.0147 mg/ml ; 0.0000564 mol/l |
Class? Solubility class: Log S scale |
Moderately 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) |
Yes |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
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 |
-5.89 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 |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.08 |
* 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 |
---|---|---|
22.18 g (99%) | In 1,4-dioxane; hydrogenchloride; ethanol; | Step A: 1H-indole-2,5-dicarboxylic acid diethyl ester 16 A suspension of 1H-Indole-2,5-dicarboxylic acid 2-ethyl ester (20.0 g, 85.75 mmole) in a saturated HCl/EtOH (200 ml) was stirred at 55 C. for 24 h and evaporated in vacuo to dryness. The residue was freeze-dried from dioxane to give 22.18 g (99%) of 1H-indole-2,5-dicarboxylic acid diethyl ester, 16 as white powder. MS: 262.12 (M+H). 1H-NMR (DMSO-d6): δ12.23 (s, 1H, H-1, indole); 8.34 (m, 1H, H-4, indole); 7.83 (m, 1H, H-6, indole); 7.49 (m, 1H, H-7, indole); 7.30 (s, 1H, H-3, indole); 4.31 (m, 4H, -O2CH3); 1.32 (m, 4H, -OCH23). |
22.18 g (99%) | In 1,4-dioxane; hydrogenchloride; ethanol; | (A) 1H-Indole-2,5-dicarboxylic acid diethyl ester, 16 A suspension of 1H-Indole-2,5-dicarboxylic acid 2-ethyl ester (20.0 g, 85.75 mmole) in a saturated HCl/EtOH (200 ml) was stirred at 55C. for 24 h and evaporated in vacuo to dryness. The residue was freeze-dried from dioxane to give 22.18 g (99%) of 1H-indole-2,5-dicarboxylic acid diethyl ester, 16 as white powder. MS: 262.12 (M+H). 1-NMR (DMSO-d6): 12.23 (s, 1H, H-1, indole); 8.34 (m, 1H, H-4, indole); 7.83 (m, 1H, H-6, indole); 7.49 (m, 1H, H-7, indole); 7.30 (s, 1H, H-3, indole); 4.31 (m, 4H, -OCH2CH3); 1.32 (m, 4H, -OCH2CH3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
800 mg (97%) | With methyl iodide; In ethyl acetate; N,N-dimethyl-formamide; | Step B: 1-Methyl-<strong>[127221-02-7]indole-2,5-dicarboxylic acid diethyl ester</strong> 17 Sodium hydride (60%-suspension, 144 mg, 3.6 mmole) was added to a stirred solution of 1H-<strong>[127221-02-7]indole-2,5-dicarboxylic acid diethyl ester</strong> 16 (784 mg, 3.0 mmole) in dry DMF (15.0 ml) and kept at ambient temperature for 30 min. To a resulted reaction mixture MeI (280 μl, 4.5 mmol) was added and kept at ambient temperature for 16 hours and evaporated. The residue was suspended in AcOEt (100 ml) and washed with water (2*20 ml), 0.01 M HCl (3*20 ml) and brine (2*100 ml). The organic layer was dried over sodium sulfate and evaporated to give 800 mg (97%) of 1-methyl-<strong>[127221-02-7]indole-2,5-dicarboxylic acid diethyl ester</strong> 17 as a yellow oil. 1H-NMR (DMSO-d6): δ8.45 (m, 1H, H-4, indole); 8.03 (m, 1H, H-6, indole); 7.40 (m, 1H, H-7, indole); 7.38 (s, 1H, H-3, indole); 4.40 (m, 4H, -O2CH3); 4.10 (s, 3H, N3, indole); 1.42 (m, 4H, -OCH23). |
800 mg (97%) | With methyl iodide; In ethyl acetate; N,N-dimethyl-formamide; | (B) 1-Methyl-<strong>[127221-02-7]indole-2,5-dicarboxylic acid diethyl ester</strong>, 17 Sodium hydride (60%-suspension, 144 mg, 3.6 mmole) was added to a stirred solution of 1H-<strong>[127221-02-7]indole-2,5-dicarboxylic acid diethyl ester</strong> 16 (784 mg, 3.0 mmole) in dry DMF (15.0 ml) and kept at ambient temperature for 30 min. To a resulted reaction mixture MeI (280 μl, 4.5 mmol) was added and kept at ambient temperature for 16 hours and evaporated. The residue was suspended in AcOEt (100 ml) and washed with water (2*20 ml), 0.01 M HCl (3*20 ml) and brine (2*100 ml). The organic layer was dried over sodium sulfate and evaporated to give 800 mg (97%) of 1-methyl-<strong>[127221-02-7]indole-2,5-dicarboxylic acid diethyl ester</strong> 17 as a yellow oil. 1-NMR (DMSO-d6): 8.45 (m, 1H, H-4, indole); 8.03 (m, 1H, H-6, indole); 7.40 (m, 1H, H-7, indole); 7.38 (s, 1H, H-3, indole); 4.40 (m, 4H, -OCH2CH3); 4.10 (s, 3H, NCH3, indole); 1.42 (m, 4H, -OCH2CH3). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
34% | With oxygen; palladium diacetate; acetic acid; In dimethyl sulfoxide; at 70℃; for 24h;Schlenk technique; Molecular sieve; | Take a 25 mL Schlenk reaction tube and add 66 mg of ethyl 4-aminobenzoate, 9 mg of palladium acetate and 80 mg of molecular sieve.93 mg of ethyl 2-oxopropionate, 96 mg of acetic acid and 2 mL of dimethyl sulfoxide were injected, followed by a 200 mL oxygen balloon, and stirred at 70 C for 24 hours.After the reaction was completed, 15 mL of ethyl acetate was added to dilute the reaction solution, and the filtrate was washed twice with 10 mL of saline.The organic phase was separated, and the aqueous phase was extracted with ethyl acetate.Column chromatography was carried out to obtain the objective product pure product 35 mg, yield 34%. |
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