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Chemical Structure| 16644-30-7 Chemical Structure| 16644-30-7

Structure of 16644-30-7

Chemical Structure| 16644-30-7

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Product Details of [ 16644-30-7 ]

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

Safety of [ 16644-30-7 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H314
Precautionary Statements:P305+P351+P338
Class:8
UN#:3261
Packing Group:

Computational Chemistry of [ 16644-30-7 ] Show Less

Physicochemical Properties

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
Ertl P. et al. 2000 J. Med. Chem.

83.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.91
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

1.8
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.7
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

0.35
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

0.35
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.02

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.43
Solubility 0.801 mg/ml ; 0.00372 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-3.16
Solubility 0.148 mg/ml ; 0.000685 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-2.18
Solubility 1.42 mg/ml ; 0.00661 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.34 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

4.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.97

Application In Synthesis of [ 16644-30-7 ]

* 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.

  • Downstream synthetic route of [ 16644-30-7 ]

[ 16644-30-7 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 16644-30-7 ]
  • [ 5418-63-3 ]
  • [ 38147-35-2 ]
  • 2
  • [ 16644-30-7 ]
  • [ 72462-36-3 ]
  • [ 72462-22-7 ]
  • 3
  • [ 16644-30-7 ]
  • 2,3,3-trimethyl-1-phenyl-3<i>H</i>-indolium; iodide [ No CAS ]
  • [ 72462-30-7 ]
  • 5
  • [ 16644-30-7 ]
  • [ 5732-47-8 ]
  • [ 141620-27-1 ]
  • 6
  • [ 16644-30-7 ]
  • Silver nonadecanoate [ No CAS ]
  • [ 126062-55-3 ]
  • 7
  • [ 16644-30-7 ]
  • [ 18268-45-6 ]
  • [ 88253-65-0 ]
  • 10
  • [ 16644-30-7 ]
  • [ 24685-73-2 ]
  • n-hexadecyloxymethyl-3 nitro-5 salicylaldehyde [ No CAS ]
  • 11
  • [ 107-30-2 ]
  • [ 97-51-8 ]
  • [ 16644-30-7 ]
YieldReaction ConditionsOperation 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).

  • 13
  • [ 16644-30-7 ]
  • 3,3-dimethyl-1-octadecyl-2,3-dihydroindole [ No CAS ]
  • [ 146904-81-6 ]
  • 14
  • [ 16644-30-7 ]
  • [ 23978-55-4 ]
  • 7,16-bis(2-hydroxy-3-formyl-5-nitrobenzyl)-1,4,10,13-tetraoxa-7,16-diazacyclooctadecane [ No CAS ]
  • 15
  • [ 36429-27-3 ]
  • [ 16644-30-7 ]
  • C35H49ClN2O3 [ No CAS ]
  • 17
  • [ 16644-30-7 ]
  • [ 54533-83-4 ]
  • [ 248936-95-0 ]
  • 19
  • [ 124-21-0 ]
  • [ 16644-30-7 ]
  • [ 288852-83-5 ]
  • 20
  • [ 118-12-7 ]
  • [ 16644-30-7 ]
  • [ 38147-35-2 ]
YieldReaction ConditionsOperation 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).
  • 21
  • [ 16644-30-7 ]
  • [ 81526-29-6 ]
  • [ 420787-36-6 ]
  • 22
  • [ 16644-30-7 ]
  • [ 143445-56-1 ]
  • C23H24ClIN2O4 [ No CAS ]
  • 23
  • [ 16644-30-7 ]
  • [ 740810-00-8 ]
  • [ 740810-01-9 ]
  • 24
  • [ 16644-30-7 ]
  • [ 23978-55-4 ]
  • [ 883867-73-0 ]
  • [ 190781-92-1 ]
  • 25
  • [ 110-86-1 ]
  • [ 16644-30-7 ]
  • 1-(3-formyl-2-hydroxy-5-nitrobenzyl)pyridinium chloride [ No CAS ]
  • 26
  • [ 110-86-1 ]
  • [ 118-12-7 ]
  • [ 16644-30-7 ]
  • [ 16150-39-3 ]
  • 27
  • [ 16644-30-7 ]
  • [ 16150-39-3 ]
  • 28
  • [ 100-02-7 ]
  • [ 16644-30-7 ]
  • 29
  • [ 16644-30-7 ]
  • [ 883867-76-3 ]
  • 30
  • [ 16644-30-7 ]
  • C35H48N4O9 [ No CAS ]
  • 31
  • [ 16644-30-7 ]
  • [ 849113-99-1 ]
  • 32
  • [ 16644-30-7 ]
  • C32H40N6O6 [ No CAS ]
  • 34
  • [ 16644-30-7 ]
  • C44H46N6O6 [ No CAS ]
  • 35
  • [ 16644-30-7 ]
  • C48H54N6O8 [ No CAS ]
 

Historical Records

Technical Information

• Acidity of Phenols • Alkyl Halide Occurrence • Barbier Coupling Reaction • Baylis-Hillman Reaction • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Bucherer-Bergs Reaction • Chan-Lam Coupling Reaction • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Chaykovsky Reaction • Corey-Fuchs Reaction • Electrophilic Substitution of the Phenol Aromatic Ring • Etherification Reaction of Phenolic Hydroxyl Group • Fischer Indole Synthesis • Friedel-Crafts Reaction • General Reactivity • Grignard Reaction • Halogenation of Phenols • Hantzsch Dihydropyridine Synthesis • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Hydrogenolysis of Benzyl Ether • Julia-Kocienski Olefination • Kinetics of Alkyl Halides • Knoevenagel Condensation • Kumada Cross-Coupling Reaction • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Mukaiyama Aldol Reaction • Nozaki-Hiyama-Kishi Reaction • Oxidation of Phenols • Passerini Reaction • Paternò-Büchi Reaction • Pechmann Coumarin Synthesis • Petasis Reaction • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reformatsky Reaction • Reimer-Tiemann Reaction • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Stetter Reaction • Stille Coupling • Stobbe Condensation • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Tebbe Olefination • Ugi Reaction • Vilsmeier-Haack Reaction • Wittig Reaction • Wolff-Kishner Reduction

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