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Chemical Structure| 5417-17-4 Chemical Structure| 5417-17-4

Structure of 5417-17-4

Chemical Structure| 5417-17-4

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Product Details of [ 5417-17-4 ]

CAS No. :5417-17-4
Formula : C9H9ClO3
M.W : 200.62
SMILES Code : O=CC1=CC=C(OC)C(OC)=C1Cl
MDL No. :MFCD00084942
InChI Key :SAWHDJTZESXNMM-UHFFFAOYSA-N
Pubchem ID :79445

Safety of [ 5417-17-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 5417-17-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 49.82
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

35.53 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.08
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

1.95
Log Po/w (WLOGP)?

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

2.17
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.

1.4
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

2.63
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.05

Water Solubility

Log S (ESOL):?

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

-2.46
Solubility 0.702 mg/ml ; 0.0035 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.

-2.32
Solubility 0.958 mg/ml ; 0.00478 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

-3.22
Solubility 0.12 mg/ml ; 0.0006 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

Yes
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.

-6.14 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

1.0 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)

1.73

Application In Synthesis of [ 5417-17-4 ]

* 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 [ 5417-17-4 ]

[ 5417-17-4 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 79-24-3 ]
  • [ 5417-17-4 ]
  • [ 119749-94-9 ]
  • 3
  • [ 75-52-5 ]
  • [ 5417-17-4 ]
  • [ 859739-05-2 ]
  • 4
  • [ 93983-14-3 ]
  • [ 5417-17-4 ]
  • 5
  • [ 5417-17-4 ]
  • [ 37687-57-3 ]
  • 6
  • [ 5417-17-4 ]
  • [ 52009-53-7 ]
YieldReaction ConditionsOperation in experiment
96% With sodium chlorite; aminosulfonic acid; In 1,4-dioxane; water; at 0℃; for 0.5h;Inert atmosphere; To a solution of 4 (20.06g, 100mmol) in 1,4-dioxane (300mL) were added a solution of sulfamic acid (21.36g, 220mmol) in water (200mL) and NaClO2 (19.9g, 220mmol) in water (100mL) at 0°C. After stirring for 30minat 0°C, the mixture was quenched by a solution of sodium bisulfite (45.8g, 440mmol) in water (200mL). The aqueous layer was extracted with EtOAc and the combined extracts were washed with water and brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo to afford 5 (20.74g, 96percent). 1H NMR (DMSO?d6) delta: 13.04 (br s, 1H), 7.63 (d, J=8.9Hz, 1H), 7.11 (d, J=8.9Hz, 1H), 3.89 (s, 3H), 3.74 (s, 3H).
  • 7
  • [ 5417-17-4 ]
  • [ 99854-17-8 ]
  • 8
  • [ 82668-20-0 ]
  • [ 5417-17-4 ]
  • 9
  • [ 5417-17-4 ]
  • [ 32864-11-2 ]
YieldReaction ConditionsOperation in experiment
48.1% With boron tribromide; In dichloromethane; at 0 - 25℃; for 4h; <strong>[5417-17-4]2-chloroveratraldehyde</strong> (3 g, 15.0 mmol) wasdissolved in DCM (30 mL). BBr3 (4.61 mL, 48mmol) was added dropwise at 0°C. After addition,the reaction mixture was warmed to room temperature and stirred for 4 h. The reaction mixture wasextracted with EA and the organic phase was washed with water and brine, dried over anhydrousNa2SO4, filtered and then the filtrate was concentrated in vacuo. The residue was purified bychromatography on silica gel with DCM/MeOH (50:1) to give 73a-2 (1.24 g, 48.1percent) as a whitesolid.
  • 10
  • [ 5417-17-4 ]
  • [ 93983-13-2 ]
YieldReaction ConditionsOperation in experiment
With sodium tetrahydroborate; In ethanol; at 20℃; <strong>[5417-17-4]2-Chloro-3,4-dimethoxybenzaldehyde</strong> (2.5 g, 12.4 mmol) was dissolved in ethanol (50 ml), sodium borohydride (930 mg, 25 mmol) was added, and the mixture was stirred overnight at room temperature. A treatment according to a conventional method using ethyl acetate as an extraction solvent gave a crude product. The obtained crude product was dissolved in thionyl chloride (5 ml) and, after stirring at room temperature for 4 hr, treated according to a conventional method using ethyl acetate as an extraction solvent. The obtained crude product was dissolved in dimethyl sulfoxide (30 ml), sodium cyanide (610 mg, 12.4 mmol) was added, and the mixture was stirred overnight at room temperature. A treatment according to a conventional method using ethyl acetate as an extraction solvent gave a crude product, which was successively purified by silica gel column chromatography to give a nitrile intermediate (830 mg, 3.93 mmol)
With sodium tetrahydroborate; In dichloromethane; at 20℃; for 0.5h; General procedure: To a solution of various benzaldehydes 4aew (10 mmol) dissolved in methanol (50 mL) was added sodium borohydride (20 mmol) at room temperature, and the mixturewas stirred at the same temperature for 30 min and concentrated under reduced pressure. The residue was diluted with methylene chloride (500 mL) and washed with water, and dried over anhydrous Na2SO4, and concentrated under reduced pressure to give the corresponding crude phenylmethanols 5a-w
  • 11
  • [ 120-14-9 ]
  • [ 5417-17-4 ]
  • 12
  • [ 37687-57-3 ]
  • [ 77-78-1 ]
  • [ 5417-17-4 ]
  • 13
  • [ 5417-17-4 ]
  • [ 106-65-0 ]
  • [ 103346-93-6 ]
  • 14
  • [ 5417-17-4 ]
  • [ 543-24-8 ]
  • 4-[1-(2-Chloro-3,4-dimethoxy-phenyl)-meth-(Z)-ylidene]-2-methyl-4H-oxazol-5-one [ No CAS ]
  • 16
  • [ 5417-17-4 ]
  • Fmoc-D-Arg(Pmc)-Wang resin [ No CAS ]
  • MK-34 [ No CAS ]
  • 17
  • [ 5417-17-4 ]
  • Fmoc-L-Arg(Pbf)-OH [ No CAS ]
  • MK-26 [ No CAS ]
  • 18
  • [ 5417-17-4 ]
  • [ 2200-97-7 ]
  • [ 64-19-7 ]
  • N-(2-chloro-3,4-dimethoxybenzylideneamino)guanidinium acetate [ No CAS ]
  • 19
  • [ 68-12-2 ]
  • [ 459410-39-0 ]
  • [ 5417-17-4 ]
  • 20
  • [ 5417-17-4 ]
  • [ 768-94-5 ]
  • 1-[(2-chloro-3,4-dimethoxybenzylidene)amino]adamantane [ No CAS ]
  • 21
  • [ 5417-17-4 ]
  • [ 13074-39-0 ]
  • 2-[(2-chloro-3,4-dimethoxybenzylidene)amino]adamantane [ No CAS ]
  • 22
  • [ 5417-17-4 ]
  • [ 36826-58-1 ]
  • N-(2-chloro-3,4-dimethoxybenzylideneamino)-N'-hydroxyguanidine tosylate [ No CAS ]
  • 23
  • [ 5417-17-4 ]
  • [ 100945-15-1 ]
  • (Z)-2-benzyloxycarbonylamino-3-(2-chloro-3,4-dimethoxy-phenyl)-acrylic acid methyl ester [ No CAS ]
  • 24
  • [ 5417-17-4 ]
  • [ 108-24-7 ]
  • acetic acid acetoxy-(2-chloro-3,4-dimethoxy-phenyl)-methyl ester [ No CAS ]
  • 26
  • [ 5417-17-4 ]
  • 3-(2-Chloro-3,4-dimethoxy-phenyl)-2-oxo-propionic acid [ No CAS ]
  • 27
  • [ 5417-17-4 ]
  • 1-(2-Chloro-3,4-dimethoxy-benzyl)-2,6,9-trimethyl-2,3,4,9-tetrahydro-1H-β-carboline; hydrochloride [ No CAS ]
  • 28
  • [ 5417-17-4 ]
  • 1-(2-Chloro-3,4-dimethoxy-benzyl)-2,3,4,9-tetrahydro-1H-β-carboline [ No CAS ]
  • 29
  • [ 5417-17-4 ]
  • 1-[(2-chloro-3,4-dimethoxyphenyl)methyl]-2,3,4,9-tetrahydro-6-methyl-1H-pyrido[3,4-b]indole [ No CAS ]
  • 30
  • [ 5417-17-4 ]
  • 1-(2-Chloro-3,4-dimethoxy-benzyl)-2,6-dimethyl-2,3,4,9-tetrahydro-1H-β-carboline [ No CAS ]
  • 31
  • [ 621-59-0 ]
  • [ 5417-17-4 ]
YieldReaction ConditionsOperation in experiment
With chlorine; In N,N-dimethyl-formamide; Step 1. Preparation of 2-chloro-3-hydroxy-4-methoxybenzaldehyde Chlorine gas is introduced into a solution of 3-hydroxy-4-methoxybenzaldehyde in N,N-dimethylformamide at -10° to -30° C. When the addition of chlorine is complete, the reaction mixture is stirred at -25° C. for 30 minutes and, then, poured into water. The product is separated by filtration and washed with water. The wet product may be dried or used directly in the next step. Average yield, 73percent. Step 2. Preparation of 2-chloro-3,4-dimethoxybenzaldehyde (1)
With chlorine; potassium carbonate; dimethyl sulfate; In N-methyl-acetamide; chloroform; water; EXAMPLE 2 Isovanillin (200 g, 1.32 mole) was suspended in 1200 cc chloroform. Chlorine (103 g, 1.45 mole) was added by means of 3 500 cc portions of carbon tetrachloride, in which it was dissolved. The suspension was stirred vigorously during the addition and the reaction was kept around 25° by a water bath. The suspension was stirred for 22 minutes after the completion of the addition of chlorine. The precipitate was filtered and crystallized from methanol, then recrystallized from isopropanol/ethyl acetate. Yield 98.7 g (40percent, m.p. 204°-206°) of 2-chloro-3-hydroxy-4-methoxybenzaldehyde. The aldehyde product (189.3 g, 1.02 mole) was suspended in 1 l. of dry dimethylformamide, 350 g of potassium carbonate was added. 145 cc (124 g, 1.54 mole) of dimethyl sulfate was added dropwise over a 20 minute period. After the addition the reaction was heated on the steam bath for 5 minutes. 70 cc of water were added and the reaction was again heated for 5 minutes on the steam bath. The mixture was then poured into ice water and the precipitate was collected. It was crystallized from acetic acid/water (800 cc-50 cc). A second crop was obtained from the mother liquor. Yield 180 g (90percent) of 2-chloro-3,4-dimethoxybenzaldehyde after drying, m.p. 69°-70°.
With chlorine; potassium carbonate; dimethyl sulfate; In N-methyl-acetamide; chloroform; water; EXAMPLE 1 Isovanillin (200 g, 1.32 mole) was suspended in 1200 cc chloroform. Chlorine (103 g, 1.45 mole) was added by means of 3 500 cc portions of carbon tetrachloride, in which it was dissolved. The suspension was stirred vigorously during the addition and the reaction was kept around 25° by a water bath. The suspension was stirred for 22 minutes after the completion of the addition of chlorine. The precipitate was filtered and crystallized from methanol, then recrystallized from isopropanol/ethyl acetate. Yield 98.7 g (40percent, m.p. 204-206°) of 2-chloro-3-hydroxy-4-methoxybenzaldehyde. The aldehyde product (189.3 g, 1.02 mole) was suspended in 1 l. of dry dimethylformamide, 350 g of potassium carbonate was added. 145 cc (124 g, 1.54 mole) of dimethyl sulfate was added dropwise over a 20 minute period. After the addition the reaction was heated on the steam bath for 5 minutes. 70 cc of water were added and the reaction was again heated for 5 minutes on the steam bath. The mixture was then poured into ice water and the precipitate was collected. It was crystallized from acetic acid/water (800 cc-50 cc). A second crop was obtained from the mother liquor. Yield 180 g (90percent) of 2-chloro-3,4-dimethoxybenzaldehyde after drying, m.p. 69°-70°.
  • 32
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  • [ 67287-37-0 ]
  • 33
  • [ 5417-17-4 ]
  • [ 67287-38-1 ]
 

Historical Records

Technical Information

• Alkyl Halide Occurrence • Barbier Coupling Reaction • Baylis-Hillman Reaction • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Bucherer-Bergs Reaction • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Chaykovsky Reaction • Corey-Fuchs Reaction • Fischer Indole Synthesis • Friedel-Crafts Reaction • General Reactivity • Grignard Reaction • 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 • Nomenclature of Ethers • Nozaki-Hiyama-Kishi Reaction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Preparation of Amines • Preparation of Ethers • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions of Ethers • Reformatsky 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

Categories

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[ 5417-17-4 ]

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