Structure of 98592-34-8
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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. : | 98592-34-8 |
Formula : | C9H6ClNO2 |
M.W : | 195.60 |
SMILES Code : | O=C(OC)C1=CC=C(C#N)C=C1Cl |
MDL No. : | MFCD14635863 |
InChI Key : | GLZBUNHGODEJPT-UHFFFAOYSA-N |
Pubchem ID : | 53845357 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.11 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 47.45 |
TPSA ? Topological Polar Surface Area: Calculated from |
50.09 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.0 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.15 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.0 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.86 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.33 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.27 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.25 |
Solubility | 0.111 mg/ml ; 0.000567 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.87 |
Solubility | 0.0263 mg/ml ; 0.000134 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.18 |
Solubility | 0.129 mg/ml ; 0.000661 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 |
-5.26 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 |
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) |
1.77 |
* 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% | Lithium hydroxide (1.12 g, 26.69 mmol) was added to a solution of 2-chloro-4-cyano-benzoic acid methyl ester (2.60 g, 13.29 mmol) in dioxan/water (4:1, 100ml). The mixture was stirred at room temperature for 3h and concentrated in vacuo. The residue was partitioned between 1N hydrochloric acid and chloroform and the organic layer was washed with brine and concentratedin vacuo. The residue was recrystallised from a mixture of dioxan and pet. ether to give a pale orange solid identified as 2-chloro-4-cyanobenzoic acid (2.33 g, 97%). | |
63.3% | Intermediate 125b was dissolved in a 0.5molar 1 : 1 mixture of MeOH / THF and LiOH.H20 (302 mg, 7.21 mmol. The reaction was stirred for 5hrs before the solvent was removes under vaccuum.The residue was suspended in water and acidified with aqueous HCI (2M). A pink precipitate was filtered off and dried under HV + cold trap to yield intermediate 125c (569.2 mg, 3.04 mmol, 63.3 % yield) as pinkish solid.1 H NMR (400 MHz, DMSO-c 6) delta ppm 13.95 (br. S., 1 H), 8.18 (s, 1 H), 7.85 - 7.96 (m, 2 H). RtMSi= 1.21 min., [M+H]+ = 182.1. | |
55% | With lithium hydroxide; water; In tetrahydrofuran; for 18h; | 2-Chloro-4-cyanobenzoic acid Lithium hydroxide monohydrate (1.18g, 28mmol) was added to a solution of 2-chloro-4-cyanobenzoic acid methyl ester (2.61g, 13mmol) in a mixture of THF and water (4:1, 100ml) and stirred for 18h. The mixture was reduced in vacuo, the residue was acidified with 1N hydrochloric acid and extracted with a mixture of methanol and chloroform (5:95). The organic extracts were washed with brine, dried and reduced. The residue was recrystallized from dioxan/pet. ether to give a pale orange solid identified as 2-chloro-4-cyanobenzoic acid, yield 1.34g, 55%. |
With sodium hydroxide; In methanol; water; | EXAMPLE 76 2-Chloro-4-cyanobenzoic Acid To a stirred solution of 2-chloro-4-cyanobenzoic acid, methyl ester (24.3 g) in methanol (150 ml) was added 2.5N sodium hydroxide (54.5 ml). After stirring at room temperature. for 45 minutes, the solvent was removed in vacuo. The residue was dissolved in water, cooled in an ice bath, and made acidic with 2N hydrochloric acid (14 ml). The resulting precipitate was filtered and dried in vacuo to yield the title compound as a solid (22.55 g) m.p. 154-158 C. | |
To a stirred solution of 2-chloro-4-cyanobenzoic acid, methyl ester (24.3 g) in methanol (150 ml) was added 2.5N sodium hydroxide (54.5 ml). After stirring at room temperature. for 45 minutes, the solvent was removed in vacuo. The residue was dissolved in water, cooled in an ice bath, and made acidic with 2N hydrochloric acid (14 ml). The resulting precipitate was filtered and dried in vacuo to yield the title compound as a solid (22.55 g) m.p. 154-158 C. |
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