Structure of 7126-50-3
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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. : | 7126-50-3 |
Formula : | C8H9NO3 |
M.W : | 167.16 |
SMILES Code : | O=C(C1=CC=C(C=O)N1)OCC |
MDL No. : | MFCD00159462 |
InChI Key : | HTPFMOGFQKDFHX-UHFFFAOYSA-N |
Pubchem ID : | 321485 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.25 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 42.27 |
TPSA ? Topological Polar Surface Area: Calculated from |
59.16 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.71 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.06 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.0 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.23 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.73 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.05 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.59 |
Solubility | 4.31 mg/ml ; 0.0258 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.89 |
Solubility | 2.14 mg/ml ; 0.0128 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.03 |
Solubility | 1.56 mg/ml ; 0.00933 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 |
-6.57 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 |
1.0 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 |
---|---|---|
50%; 7% | A-6 5-Formyl-1H-pyrrole-2-carboxylic acid To a solution of dimethylformamide (21 mL, 0.27 mol) in 75 mL of dichloroethane was added a solution of phosphorus oxychloride (25 mL, 0.27 mol) in 75 mL of dichloroethane at 0 oC. The mixture was stirred at room temperature for 30 minutes and cooled to 0 oC. To the mixture was added a solution of ethyl pyrrole-2-carboxylate (25 g, 0.18 mol) in 50 mL of dichloroethane dropwise. The resulting mixture was stirred at room temperature for 30 minutes and then at 40 oC for 1 hour. The mixture was poured into ice and basified to pH 11 with 5 N sodium hydroxide solution. The mixture was extracted with ethyl acetate and the extract washed with water and brine and dried over anhydrous sodium sulfate. The two products were separated by column chromatography (1:3 ethyl acetate:hexane) to give 15 g (50% yield) of 5-formyl-1H-pyrrole-2-carboxylic acid ethyl ester and 2 g (7% yield) of 4-formyl-1H-pyrrole-2-carboxylic acid ethyl ester. 1H-NMR (300 MHz, dimethylsulfoxide) δ 13.02 (br s, 1H, NH), 9.69 (s, 1H, CHO), 6.95 (d, 1H), 6.86 (d, 1H), 4.27 (q, 2H, CH3), 1.28 (t, 3H, CH3). MS m/z 167 [M+]. | |
50%; 7% | To a solution of dimethylformamide (21 mL, 0.27 mol) in 75 mL of dichloroethane was added a solution of phosphorus oxychloride (25 mL, 0.27 mol) in 75 mL of dichloroethane at 0 oC. The mixture was stirred at room temperature for 30 minutes and cooled to 0 oC. To the mixture was added a solution of ethyl pyrrole-2-carboxylate (25 g, 0.18 mol) in 50 mL of dichloroethane dropwise. The resulting mixture was stirred at room temperature for 30 minutes and then at 40 oC. for 1 hour. The mixture was poured into ice and basified to pH 11 with 5 N sodium hydroxide solution. The mixture was extracted with ethyl acetate and the extract washed with water, brine and dried over anhydrous sodium sulfate. The two products were separated by column chromatography (1:3 ethyl acetate:hexane) to give 15 g (50% yield) of 5-formyl-1H-pyrrole-2-carboxylic acid ethyl ester and 2 g (7% yield) of 4-formyl-1H-pyrrole-2-carboxylic acid ethyl ester. 1H-NMR (5-formyl-1H-pyrrole-2-carboxylic acid ethyl ester) (300 MHz, dimethylsulfoxide) δ 13.02 (br s, 1H, NH), 9.69 (s, 1H, CHO), 6.95 (d, 1H), 6.86 (d, 1H), 4.27 (q, 2H, CH3), 1.28 (t, 3H, CH3). MS m/z 167 [M+]. | |
50%; 7% | [0179] To a solution of dimethylformamide (21 mL, 0.27 mol) in 75 mL of dichloroethane was added a solution of phosphorus oxychloride (25 mL, 0.27 mol) in 75 mL of dichloroethane at 0 C. The mixture was stirred at room temperature for 30 minutes and cooled to 0 C. To the mixture was added a solution of ethyl pyrrole-2-carboxylate (25 g, 0.18 mol) in 50 mL of dichloroethane dropwise. The resulting mixture was stirred at room temperature for 30 minutes and then at 40 C. for 1 hour. The mixture was poured into ice and basified to pH 11 with 5 N sodium hydroxide solution. The mixture was extracted with ethyl acetate and the extract washed with water and brine and dried over anhydrous sodium sulfate. The two products were separated by column chromatography (1:3 ethyl acetate:hexane) to give 15 g (50% yield) of 5-formyl-1H-pyrrole-2-carboxylic acid ethyl ester and 2 g (7% yield) of 4-formyl-1H-pyrrole-2-carboxylic acid ethyl ester. 1H-NMR (300 MHz, dimethylsulfoxide) δ 13.02 (br s, 1H, NH), 9.69 (s, 1H, CHO), 6.95 (d, 1H), 6.86 (d, 1H), 4.27 (q, 2H, CH3), 1.28 (t, 3H, CH3). MS M/Z 167 [M+]. |
46%; 42% | With trichlorophosphate; at 30℃;Inert atmosphere; Cooling with ice; | To an ice-cooled solution of ethyl 1H-pyrrole-2-carboxylate2 (10 g, 72 mmol) in dry DMF (129.3 mL), freshly distilled phosphorus oxychloride (POCl3, 20.1 mL, 216 mmol) was added dropwise under argon atmosphere. After the completion of the addition, the cooling bath was removed and the reaction mixture was stirredat 30 C for 21 h. Then, the mixture was gradually added to ice-water, the pH was adjusted to pH=7 with 25 % aq. NH3 and the aqueous solution was extracted with DCM (3×). The combined organic layers were washed with saturated aqueous NaHCO3 (1×) and brine (1×), dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. The resulting oily residue was purified by silica gel flash column chromatography (DCM/MeOH 98:2) to afford 4 (5 g, red-browns olid, 42 %) and ethyl 5-formyl-1H-pyrrole-2-carboxylate (5.5 g, red-brown solid, 46 %).For compound 4: Rf (toluene/EtOAc 8:2) 0.13. mp 103-104 C. IR (KBr): max 3175, 2881, 1705, 1651, 1269 cm-1. 1H NMR (CDCl3, 400 MHz): 10.10 (br s, 1H), 9.85 (s, 1H), 7.58 (dd, J = 3.3 Hz,J = 1.5 Hz, 1H), 7.33-7.32 (m, 1H), 4.36 (q, J = 7.1 Hz, 2H), 1.37 (t, J = 7.1 Hz,3H). 13C NMR (CDCl3, 100 MHz): 185.82, 161.12, 128.61, 127.69, 125.26, 114.28,61.31, 14.45. MS (ESI+) (m/z): 168.53 [M+H]+. HRMS-ESI (m/z): [M+Na]+ calcd for C8H9NO3: 190.04746, found: 109.04756. |
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