Structure of 13452-14-7
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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. : | 13452-14-7 |
Formula : | C9H7NO3 |
M.W : | 177.16 |
SMILES Code : | CC1=NC2=C(O1)C=C(C=C2)C(=O)O |
MDL No. : | MFCD07787266 |
InChI Key : | GFYDDTFAVDJJAI-UHFFFAOYSA-N |
Pubchem ID : | 18475689 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.11 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 45.93 |
TPSA ? Topological Polar Surface Area: Calculated from |
63.33 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.59 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.69 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.83 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.9 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.69 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.54 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.45 |
Solubility | 0.629 mg/ml ; 0.00355 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.63 |
Solubility | 0.411 mg/ml ; 0.00232 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.67 |
Solubility | 0.376 mg/ml ; 0.00212 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 |
-6.18 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 |
0.56 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 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) |
2.17 |
* 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% | Stage #1: With sodium hydroxide In ethanol; water at 20℃; for 2 h; Stage #2: With hydrogenchloride In ethanol; water |
Preparation Example K-2. 2-Methyl-benzoxazole-6-carboxylic acid To a solution of 2-methyl-benzoxazole-6-carboxylic acid methyl ester (301 mg, 1.57mmol) in ethanol (10mL) was added an aqueous solution of 2N sodium hydroxide (10mL), and the mixture was stirred for 2 hours at room temperature. 2N Hydrochloric acid was added to the reaction mixture to adjust the pH to 4, and the solution was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, then, evaporated in vacuo, and the title compound (270mg, 1.52mmol, 97percent) was obtained. This was used in the next reaction without purification. 1H-NMR Spectrum (DMSO-d6) δ (ppm): 2.64 (3H, s), 7.73 (1H, d, J=8.0Hz), 7.93(1 H, dd, J=1.2, 8.0Hz), 8.15 (1 H, d, J= 1.2Hz). |
97% | Stage #1: at 20℃; for 2 h; Stage #2: With hydrogenchloride In water |
To a solution of 2-methyl-benzoxazole-6-carboxylic acid methyl ester (301 mg, 1.57mmol) in ethanol (10mL) was added an aqueous solution of 2N sodium hydroxide (10mL), and the mixture was stirred for 2 hours at room temperature. 2N Hydrochloric acid was added to the reaction mixture to adjust the pH to 4, and the solution was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, then, evaporated in vacuo, and the title compound (270mg, 1.52mmol, 97percent) was obtained. This was used in the next reaction without purification. 1H-NMR Spectrum (DMSO-d6) δ(ppm) : 2.64 (3H, s), 7.73 (1 H, d, J=8.0Hz), 7.93(1 H, dd, J=1.2, 8.0Hz), 8.15 (1 H, d, J= 1.2Hz). |
90% | With lithium hydroxide monohydrate; water In tetrahydrofuran for 2 h; | To methyl 2-methyl-1,3-benzoxazole-6-carboxylate (8) (12.2 g, 0.064 mol) in THF (300 mL)/H2O (100 mL) was added lithium hydroxide monohydrate (5.4 g, 0.128 mol), and the mixture was vigorously stirred. After 2 h the THF was removed under vacuum. The remaining aqueous phase was acidified with HOAc and exhaustively extracted with CH2Cl2. The pooled organic extract was dried (Na2SO4) and concentrated to give a beige solid (10.2 g, 90percent yield): mp 245–246 °C (lit.40 245–246 °C); TLC (SiO2, ethyl acetate/methanol (90:10), UV) single spot Rf 0.38. 1H NMR (300 MHz, DMSO); δ 2.66 (s, 3H, NCH3), 7.75 (d, J = 8.3 Hz, 1H, H-5), 7.96 (dd, J = 8.3, 1.4 Hz, 1H, H-4), 8.16 (d, J = 0.7 Hz, 1H, H-7), 13.12 (bs, 1H, OH). |
65% | Stage #1: With lithium hydroxide monohydrate; water In tetrahydrofuran; methanol at 25℃; for 2 h; Stage #2: With hydrogenchloride In tetrahydrofuran; methanol |
To a solution of methyl 2-methylbenzo[d]oxazole-6-carboxylate (2.0 g, 10 mmol) in tetrahydrofuran/methanol/water (1: 1 : 1, 15 mL) was added lithium hydroxide hydrate (0.88 g, 21 mmol). The resulting mixture was stirred at 25 °C for 2 hours. On completion, the mixture was acidified with hydrochloric acid, resulting in formation of a solid. The solid was collected by filtration, washed with water and dried in vacuo to give compound B-130 (1.2 g, 65percent yield) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | at 100℃; for 0.0833333 h; Microwave irradiation | A heterogeneous mixture of 4-amino-3-hydroxybenzoic acid (7b) (7.732 g, 0.050 mol) and 1,1,1-trimethoxyethane (16 mL) was heated to 100 °C using a microwave (55 W) and held for 5 min. The reaction was repeated two more times (7.732 g and 7.625 g), and the combined reaction mixtures were concentrated in vacuo giving the product as a tan solid in quantitative yield: mp 245–246 °C (lit.40 245–246 °C); TLC (SiO2, ethyl acetate/methanol (90:10), UV) single spot Rf 0.38; MS MH+ 178.4. 1H NMR (300 MHz, DMSO); δ 2.66 (s, 3H, NCH3), 7.75 (d, J = 8.3 Hz, 1H, H-5), 7.96 (dd, J = 8.3, 1.4 Hz, 1H, H-7), 8.16 (d, J = 0.7 Hz, 1H, H-7), 13.12 (bs, 1H, OH). |
95% | at 100℃; for 0.0833333 h; Microwave irradiation | A solution of compound 4.1 (1.10 g) and 1,1,1-trimethoxyethane (5 mL) was heated at 100° C. for 5 minutes in a microwave. The reaction mixture was concentrated under reduced pressure to provide 1.26 g of compound 4.2 (95percent pure) as a brown powder. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.66 (s, 3H), 7.74 (d, J=8.4 Hz, 1H), 7.96 (dd, J=8.3, 1.4 Hz, 1H), 8.16 (d, J=1.4 Hz, 1H), 13.07 (s(br), 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | at 130℃; for 72 h; | (Intermediate Example 70) 2-Methylbenzoxazole-6-carboxylic acid 4-Amino-3-hydroxybenzoic acid (4.9 g) was added to acetic acid (250 ml) and stirred for 3 days at 130°C. The solution was concentrated under reduced pressure, and precipitates were collected by filtration. The precipitates were dissolved in methanol and chloroform. The solution was concentrated under reducedpressure, and precipitates were collected by filtration, washed with methanol and dried under reduced pressure to give the title compound (3.5 g, Y.: 62percent). 1H NMR; (DMSO-d6) δ (ppm): 2.6 (s, 3H), 7.7 (d, 1H), 7.9 (dd, 1H), 8.1 (d, 1H). ESI/MS (m/z): 178 (M+H)+, 176 (M-H)-. |
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