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Type | HazMat fee for 500 gram (Estimated) |
Excepted Quantity | USD 0.00 |
Limited Quantity | USD 15-60 |
Inaccessible (Haz class 6.1), Domestic | USD 80+ |
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Structure of 16644-30-7
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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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Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 16644-30-7 |
Formula : | C8H6ClNO4 |
M.W : | 215.59 |
SMILES Code : | O=CC1=CC([N+]([O-])=O)=CC(CCl)=C1O |
MDL No. : | MFCD00191331 |
InChI Key : | VPZKJFJWKLYFQD-UHFFFAOYSA-N |
Pubchem ID : | 99380 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302-H314 |
Precautionary Statements: | P305+P351+P338 |
Class: | 8 |
UN#: | 3261 |
Packing Group: | Ⅱ |
Num. heavy atoms | 14 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 52.44 |
TPSA ? Topological Polar Surface Area: Calculated from |
83.12 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.91 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.8 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.7 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.35 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.35 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.02 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.43 |
Solubility | 0.801 mg/ml ; 0.00372 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.16 |
Solubility | 0.148 mg/ml ; 0.000685 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.18 |
Solubility | 1.42 mg/ml ; 0.00661 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 |
No |
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 |
-6.34 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 |
4.0 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) |
1.97 |
* 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 |
---|---|---|
72% | aluminium trichloride; In hexane; water; | EXAMPLE 1 While cooling a mixture of 12.0 g of 5-nitrosalicylaldehyde and 100 ml of chloromethyl methyl ether in an ice bath, 43.9 g of anhydrous aluminum chloride was added in small portions to the mixture, followed by stirring at room temperature for 10 minutes and thereafter by refluxing with heating for 22 hours. The reaction mixture was then cooled in an ice bath, and 200 ml of water was added to the mixture with full stirring, whereby white crystals were separated out. The white crystals were collected and dissolved in hot hexane, and the solution was filtered. The mother liquor was thereafter cooled, giving 14.9 g of 3-chloromethyl-5-nitrosalicylaldehyde in the form of white needlelike crystals (yield 72%). 1 H-NMR(CDCl3); deltappm 4.72(s, 2H, --CH2 Cl), 8.56(s, 2H, ArH), 10.00(s, 1H, CHO), 12.10(s, 1H, OH). |
72% | aluminium trichloride; In hexane; water; | Example 1 A mixture of 12.0 g of 5-nitrosalicylaldehyde and 100 ml of chloromethyl methyl ether was cooled on an ice-bath and 43.9 g of anhydrous aluminum chloride was added in small portions. The mixture was stirred at room temperature for 10 minutes and, then, refluxed for 22 hours. This reaction mixture was cooled on an ice-bath and 200 ml of water was added with vigorous stirring, whereupon white crystals separated out. These white crystals were collected, dissolved in hot hexane and filtered and the mother liquor was cooled to give 14.9 g of 3-chloromethyl-5-nitrosalicylaldehyde as colorless needles (Yield 72%). 1H-NMR (CDCl3): deltappm 4.72 (s, 2H, -CH2Cl), 8.56 (s, 2H, ArH), 10.00 (s, 1H, CHO), 12.10 (s, 1H, OH) |
72% | aluminium trichloride; In hexane; water; | Example 1 A mixture of 12.0 g of 5-nitrosalicylaldehyde and 100 ml of chloromethyl methyl ether was cooled on an ice-bath and 43.9 g of anhydrous aluminum chloride was added in small portions. The mixture was stirred at room temperature for 10 minutes and, then, refluxed for 22 hours. This reaction mixture was cooled on an ice-bath and 200 ml of water was added with vigorous stirring, whereupon white crystals separated out. These white crystals are collected, dissolved in hot hexane and filtered and the motor liquor was cooled to give 14.9 g of 3-chloromethyl-5-nitrosalicylaldehyde as colorless needles (Yield 72%). 1H-NMR (CDCl3): deltappm 4.72 (s, 2H, -CH2Cl), 8.56 (s, 2H, ArH), 10.00 (s, 1H, CHO), 12.10 (s, 1H, OH) |
With aluminum (III) chloride; | A compound having the structure shown as the final product in the scheme detailed in FIG. 4 was synthesized and characterized. Reaction step (1) (shown in isolation in FIG. 6) proceeds well and the product was characterized by 1H NMR spectroscopy (peak obtained at MW=214). This product was readily purified by recrystallization from hot n-hexane. The yield of this reaction in our hands was not established. The literature value is 89% isolated yield. L. D. Taylor and R. B. Davis, J. Org. Chem. 1963, 28, 1713. [0074] Reaction step (2) (shown in isolation in FIG. 7) also proceeded and the crude product was purified by recrystallization from ethanol/tetrahydrofuran. Small, square-shaped orange crystals were obtained over a period of two days in ca. 12% yield. Analysis of these crystals via 1H NMR spectroscopy suggests that their crystal structure may contain tetrahydrofuran (see FIG. 8). Mass spectroscopy yielded an m/z peak at 352. Further addition of tetrahydrofuran to the ethanol mixture yielded a second crop of similar crystals. However, this second crop was coated in orange-colored viscous oil, characteristic of material that had come out of solution too quickly. This material is to be further recrystallized to improve product yield. [0075] Reaction step (3) (shown in isolation in FIG. 9) was carried out under reflux (approximately 80 C.) proceeded well and yielded a solid product as expected. Previous attempts to synthesize this compound have yielded viscous oil. Purification of the product from reaction (2) appears to lead to a purer product from reaction (3) as we obtained a solid instead of an oil. This product was analyzed by 1H NMR and by ES mass spectral analysis: FW ca. 506, [M]+504 (100%). [0076] Reaction step (4) (shown in isolation in FIG. 10) was conducted overnight at pH=10-11. However, the pH dropped to a value of 9 after 24 h. Thus, the pH was again raised to a value of ca. 10 and allowed to react for a further 24 h, during which time the reaction mixture maintained its pH value of ca. 10. It appears that at least 48 hours are necessary for the reaction to go to completion as indicated by the lack of further pH change. ES mass spectral analysis indicated a prominent peak at 701 (expected mass of the ligand+Na+). [0077] Reaction step 5 (i.e., the final reaction step shown in FIG. 4) involves the insertion of the metal to the macrocycle. The sample was run through a Chelex 100 column after first neutralizing the reaction mixture to pH=7. However, upon eluting with water, only pale yellow oil was obtained. This did not display the characteristic absorbances of ca. 510 and 550 nm upon exposure to UV-light irradiation. In addition, it was observed that a band of purple-colored material was trapped at the top of the Chelex column. Various solvents were used to try to pass this band through the column, and ethanol and chloroform each were found to be effective to elute the product. This purple-colored material displayed characteristic color changes expected for the final product. UV irradiation (described in the following example) produced a product with absorbances at ca. 510 and 550 nm. Irradiation with white light eliminates these absorbance peaks. Mass spec for the product from step 5 yielded a peak at 835 and also peak at 678 (representing either free ligand or artifactual dissociation of product during electrospray). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In tetrahydrofuran; for 4h;Heating / reflux; | A THF solution (10 ml) of <strong>[16644-30-7]3-chloromethyl-5-nitrosalicylaldehyde</strong> (50 mg, 0.23 mmol) and 1,3,3-trimethyl-2-methyleneindoline (40 mg, 0.23 mmol) was refluxed for 4 hours. Evaporation of the solvent gave 2 as a crude product, which was used for the subsequent reaction without further purification. MS(EI): 370(M+, 45), 336(72), 159(73); HRMS(EI): M+370.1096 (Calc. 370.1084); 1H NMR (CDCl3) delta1.22 (s, 3H), 1.32 (s, 3H), 2.71, (s, 3H), 4.32 (d, J=11.7 Hz, 1H), 4.38 (d, J=11.7 Hz, 1H), 5.92 (d, J=10.3 Hz, 1H), 6.55 (d, J=7.3 Hz, 1H), 6.89 (dd, J=7.3, 7.3 Hz, 1H), 6.95 (d, J=10.3 Hz, 1H), 7.09(d, J=7.3 Hz, 1H), 7.19(dd, J=7.3, 7.3 Hz, 1H), 8.00 (d, J=2.8, 1H), 8.14 (d, J=2.8 Hz, 1H). |
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