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Chemical Structure| 55304-73-9 Chemical Structure| 55304-73-9

Structure of 55304-73-9

Chemical Structure| 55304-73-9

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Product Details of [ 55304-73-9 ]

CAS No. :55304-73-9
Formula : C6H3Cl2NO
M.W : 176.00
SMILES Code : ClC1=NC(=CC=C1C=O)Cl
MDL No. :MFCD07369746
InChI Key :HWTMRGXKSANEDO-UHFFFAOYSA-N
Pubchem ID :12259383

Safety of [ 55304-73-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319
Precautionary Statements:P264-P280-P302+P352-P337+P313-P362+P364-P332+P313

Computational Chemistry of [ 55304-73-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 39.64
TPSA ?

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

29.96 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.52
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

1.6
Log Po/w (WLOGP)?

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

2.2
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.

1.0
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

2.79
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.82

Water Solubility

Log S (ESOL):?

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

-2.32
Solubility 0.848 mg/ml ; 0.00482 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.

-1.84
Solubility 2.54 mg/ml ; 0.0144 mol/l
Class?

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

Very 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

-3.2
Solubility 0.111 mg/ml ; 0.000628 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.

-6.24 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

1.0
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

2.0 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)

1.46

Application In Synthesis of [ 55304-73-9 ]

* 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 [ 55304-73-9 ]

[ 55304-73-9 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 55304-90-0 ]
  • [ 55304-73-9 ]
YieldReaction ConditionsOperation in experiment
80% With Dess-Martin periodane; In dichloromethane; at 20 - 26℃; for 2.0h; To a solution of <strong>[55304-90-0](2,6-dichloropyridin-3-yl)methanol</strong> (1.0 g, 5.62 mmol) in CH2C12 (10 ml) was added Dess-Martin reagent (4.8 g, 11.24 mmol) at 26C. After addition the mixture was stirred at room temperature for 2 h. Once the reaction was complete, the mixture was then quenched by adding 5% aqueous Na2S203 and stirred for 30 min. The resulting mixture was extracted with CH2C12 (2x30 ml). The combined organic layers were washed with saturated Na2S203 solution (50 ml), brine (30 ml), dried over Na2S04 and concentrated to give the title compound which was used in next step without further purification. (800 mg, Yield 80%). 1H NMR (400MHz, CDC13): 10.38 (s, 1H), 8.19 (d, J=8.0 Hz, 1H), 7.44 (d, J=8.0 Hz, 1H).
66% With pyridinium chlorochromate; In dichloromethane; for 2.0h; Dissolve <strong>[55304-90-0](2,6-dichloropyridin-3-yl)-methanol</strong> (876 mg, 4.92 mmol) in dichloromethane (20.mL). Add pyridium chlorochromate (2.12 g, 9.84 mmol). Stir for 2 hours. Add diethyl ether and stir for 20 minutes. Filter the mixture through a pad of Celite and silica gel and concentrate to give 2,6-dichloropyridine-3-carbaldehyde (575 mg, 66%): 1H NMR (400 MHz5 CDCl3) delta 10.39 (s, IH)5 8.18 (d, IH, J = 8.0 Hz)5 7.43 (d, IH, J = 8.0 Hz).
With manganese dioxide; In benzene; 180 g (1.01 mols) of <strong>[55304-90-0]2,6-dichloro-3-hydroxymethylpyridine</strong> are then heated under reflux for 2 hours with 600 g (6.9 mols) of manganese dioxide in 4 l of benzene. The reaction mixture is filtered while still hot and the benzene is evaporated. After drying the residue in a vacuum drying cabinet, 2,6-dichloropyridine-3-aldehyde is obtained.
  • 2
  • [ 55304-73-9 ]
  • [ 55304-90-0 ]
YieldReaction ConditionsOperation in experiment
Example 2 - Synthesis of Phantasmidine (Figure 2) 2,6-Dichloropyridine-3-pyridinemethanol (9a). A solution of 2,6- dichloropyridine-3-carboxaldehyde (8a) (950 mg, 5.40 mmol) in MeOH (10 mL) was treated with NaBH4 (205 mg, 5.40 mmol) in one portion at 0 C. The reaction was stirred at 0 C for 30 min. 10% aqueous hydrochloric acid was added dropwise to the reaction until pH 1 was reached and MeOH was removed under vacuum. The residue was extracted with CH2CI2 (50 mL x 3). The combined CH2CI2 layers were washed with H20 (50 mL) and brine (50 mL), dried (Na2S04), and concentrated to give 952 mg (99%) of 9a as a white solid, which was used directly without further purification. A small portion of crude 9a was recrystallized to give an analytical sample: mp 73-74 C (lit. 62-64 C); 1H NMR 7.88 (d, 1, J = 8.0), 7.33 (d, 1, J = 8.0), 4.78 (br s, 2), 2.21 (br s, 1, wm = 16, OH); 13C NMR 148.8, 147.8, 139.1, 133.8, 123.2, 60.9; IR 3369. The data are identical to those previously reported.
3.01 g With methanol; sodium tetrahydroborate; at 20℃; for 0.5h; [1037] NaBH4 (808 mg, 21.3 mmol) was added to a solution of 514-1 (3.10 g, 17.7 mmol) in MeOH (22 niL), which had been pre-cooled to 0 C. The mixture was allowed to reach r.t. and stirring was prolonged for 30 mins. 1 M aq. HC1 solution was added, and the organic solvent was removed under reduced pressure. The aqueous phase was extracted with DCM (3x). The combined organic portions were dried with and filtered. The volatiles were removed under reduced pressure to afford 514-2 (3.01 g). UPLC/MS(ES+): m/z 178.00 [M+H]+.
 

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Technical Information

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