Structure of 4743-17-3
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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. : | 4743-17-3 |
Formula : | C8H4ClNO3 |
M.W : | 197.58 |
SMILES Code : | ClC1=CC2=C(NC(=O)OC2=O)C=C1 |
MDL No. : | MFCD00006701 |
InChI Key : | MYQFJMYJVJRSGP-UHFFFAOYSA-N |
Pubchem ID : | 78480 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 10 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 0 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 48.11 |
TPSA ? Topological Polar Surface Area: Calculated from |
63.07 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.19 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.65 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.13 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.59 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.71 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.66 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.67 |
Solubility | 0.419 mg/ml ; 0.00212 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.59 |
Solubility | 0.51 mg/ml ; 0.00258 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.77 |
Solubility | 0.0339 mg/ml ; 0.000171 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 |
-6.33 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) |
2.48 |
* 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 |
---|---|---|
In methanol; acetic acid; N,N-dimethyl-formamide; | a) 59.3 g (0.3 mol) of 5-chloro-isatoic anhydride and 30.3 g (0.3 mol) of (S)-azetidine-2-carboxylic acid were suspended in 400 ml of N,N-dimethylformamide/acetic acid 5:1 and heated to 87-90 in an oil bath under argon for 64 hrs. The solvent was removed in a vacuum and the residue was taken up in 500 ml of methanol, whereupon the mixture was stirred at room temperature for 30 min. The white, pure crystals were filtered off under suction. The solvent was removed in a vacuum and the semi-crystalline residue was recrystallized from 60 ml of methanol (hot filtration). The products were combined and dried in a vacuum. There were obtained 61.3 g (86%) of (S)-6-chloro-1,2,4,9,10,10a-hexahydro-azeto[2,1-c][1,4]benzodiazepine-4,10-dione of m.p. 229-231 (dec.). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
19.8% | With pyridine; at 120℃; for 18h; | 5-chloroisatoic anhydride (compound 18) (1 g, 5.06 mmol) and <strong>[2886-33-1]L-aspartic acid dibenzyl ester p-toluenesulfonate salt</strong> (6) (2.98 g, 6.13 mmol) are suspended inpyridine (20 mE) to form a suspended solution, and the suspended solution is heated to 120C. and dissolved completely and reacted for 18 hours. After 18 hours, the reaction solution is cooled to room temperature, and drops of 6N HC1 are added gradually to acidiFy the reaction solution to a pH value approximately equal to 1. The acidified reaction solution is extracted by ethyl acetate (50 mEx3), and the combined organic layer is washed by saturated salt water, and then anhydrous magnesium sulfate is used for drying and filtering. The filtered solution is concentrated to obtain a crude product, and then the crude product is re-crystallized by ethyl acetate and water to obtain the final white solid product which is the compound 78 (0.36 g, 19.8%). Analysis Data of Compound 7B ?H-NMR (300 MHz, DMSO-d5): oe 2.80 (dd, 1H),2.95 (dd, 1H), 4.10 (ddd, 1H), 5.05 (s, 2H), 7.10 (d, 1H), 7.33 (m, 5H), 7.60 (dd, 1H), 7.70 (d, 1H), 8.76 (dd, 1H), 10.60 (s, NH); ?3C-NMR(75 MHz, DMSO-d5): oe 171.0, 170.3, 166.1, 136.4, 135.9, 132.7, 130.2, 129.0, 128.7, 128.4, 128.2, 128.1,121.6, 66.0, 49.0, 33.0 |
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