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Chemical Structure| 39891-13-9 Chemical Structure| 39891-13-9

Structure of 39891-13-9

Chemical Structure| 39891-13-9

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Product Details of [ 39891-13-9 ]

CAS No. :39891-13-9
Formula : C7H6ClNO2
M.W : 171.58
SMILES Code : O=C(O)CC1=CC=C(Cl)N=C1
MDL No. :MFCD01863172
InChI Key :XWVPSJPQWOVRHJ-UHFFFAOYSA-N
Pubchem ID :14071571

Safety of [ 39891-13-9 ]

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

Computational Chemistry of [ 39891-13-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 40.79
TPSA ?

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

50.19 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.18
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

1.28
Log Po/w (WLOGP)?

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

1.36
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.

0.66
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

1.69
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.23

Water Solubility

Log S (ESOL):?

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

-1.98
Solubility 1.79 mg/ml ; 0.0104 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-1.93
Solubility 2.0 mg/ml ; 0.0117 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

-2.41
Solubility 0.661 mg/ml ; 0.00385 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

No
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.

-6.44 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.

0.56

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)

1.61

Application In Synthesis of [ 39891-13-9 ]

* 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 [ 39891-13-9 ]

[ 39891-13-9 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 39891-13-9 ]
  • [ 433336-90-4 ]
YieldReaction ConditionsOperation in experiment
Intermediate 32; 2-(6-Chloropyridin-3-yl)-acetamide; To 10.0 g (58.3 mmol) (2-chloropyridyl)-5-acetic acid in 150 mL THF are added 9.45 g (58.3 mmol) CDI and the mixture is stirred at 45 C. for 1 h. Then 28.0 g (291 mmol) NH4CO3 are added and the mixture is stirred at r.t. over night. The reaction mixture is poured onto water and extracted with EtOAc. The organic layer is dried with MgSO4 and the solvent is removed in vacuo. The residue is triturated with TBME and recrystallized from EtOH.C7H7ClN2O (M=170.6 g/mol)ESI-MS: 171 M+H]+ Rf (TLC): 0.45 (silica gel, DCM/MeOH 9/1)
  • 2
  • [ 64-17-5 ]
  • [ 39891-13-9 ]
  • [ 197376-47-9 ]
YieldReaction ConditionsOperation in experiment
95% With sulfuric acid; for 4h;Reflux; To a solution of 6-chloro-3-pyridineacetic acid (1 g, 5.83 mmol) in ethanol was added sulfuric acid (1.6 ml_). The mixture was refluxed for 4 h, then cooled to room temperature and concentrated. The residue was diluted with ethyl acetate and washed with a saturated sodium hydrogen carbonate solution. The resulting mixture was dried over MgS04 and concentrated under reduced pressure to afford crude which was purified by column chromatography to afford ethyl 2-(6-chloropyridin-3-yl)acetate (1.1 g, 95 %).
95% With sulfuric acid; for 4h;Reflux; To a solution of 6-chloro-3-pyridineacetic acid (1 g, 5.83 mmol) in ethanol was added sulfuric acid (1.6 ml_). The mixture was refluxed for 4 h, then cooled to room temperature and concentrated. The residue was diluted with ethyl acetate and washed with a saturated sodium hydrogen carbonate solution. The resulting mixture was dried over magnesium sulphate and concentrated under reduced pressure to afford crude which was purified by column chromatography to afford ethyl 2-(6-chloropyridin-3-yl)acetate (1.1 g, 95 %).
95% With sulfuric acid; for 4h;Reflux; Step 1: To a solution of 6-chloro-3-pyridineacetic acid (1 g, 5.83 mmol) in ethanol was added sulfuric acid (1.6 mL). The mixture was refluxed for 4 h, then cooled to room temperature and concentrated. The residue was diluted with ethyl acetate and washed with a saturated sodium hydrogen carbonate solution. The resulting mixture was dried over MgSO4 and concentrated under reduced pressure to afford crude which was purified by column chromatography to afford ethyl 2-(6-chloropyridin-3-yl)acetate (1.1 g, 95%).
95% With sulfuric acid; for 4h;Reflux; Step 1:[0815]To a solution of 6-chloro-3-pyridineacetic acid (1 g, 5.83 mmol) in ethanol was added sulfuric acid (1.6 mL). The mixture was refluxed for 4 h, then cooled to room temperature and concentrated. The residue was diluted with ethyl acetate and washed with a saturated sodium hydrogen carbonate solution. The resulting mixture was dried over magnesium sulfate and concentrated under reduced pressure to afford crude which was purified by column chromatography to afford ethyl 2-(6-chloropyridin-3-yl)acetate (1.1 g, 95%).
87.2% With sulfuric acid; at 90℃; 2-(6-chloropyridin-3-yl)acetic acid (4g, 22.4 mmol), ethanol (20 mL) and concentrated sulfuric acid (0.4 mL) were added to a 100 mL single-mouth bottle, and heated to 90 C to react overnight. After reaction, the mixture was cooled to room temperature, neutralized with saturated sodium bicarbonate, and extracted with ethyl acetate. The organic layers were combined, the solvent was dried with rotation under vacuum under an increased pressure, and the obtained product separated by a silica gel column (petroleum ether: ethyl acetate = 5:1) to give the product (colorless oil, 3.75 g), with a yield of 87.2%. 1H NMR (400 MHz, CDCl3) delta 8.28 (d, J= 1.5 Hz, 1H), 7.61 (dd, J= 8.2, 2.1 Hz, 1H), 7.29 (d, J = 8.2 Hz, 1H), 4.16 (q, J = 7.1 Hz, 2H), 3.59 (s, 2H), 1.25 (t, J = 7.1 Hz, 3H).
79% Example 28. Synthesis of K002. To a suspension of 6-cholro-2-pyridineacetic acid methyl ester (10 g, 58.2 mmol) was added cone, sulfuric acid (30 mL) and the reaction was heated to 70 C for 4 hr. The reaction mixture was cooled to room temperature and concentrated and the resulting residue was suspended in H20 (1L) and pH was adjusted to pH = 9 with sodium carbonate. The solution was extracted with ethyl acetate. The organics were washed with brine, dried over Na2S04, filtered and concentrated to give the crude product that was purified by flash column chromatography (30% EtOAC: 70% heptanes) to give the desired product 8.58 g, 79%.LC-MS: (ES, m/z): 186 [M+H]+ 1H-NMR: (400MHz, MeCN- J, ppm): delta 3.66 (m, 5H), 7.36(d, 1H), 7.67(d, 1H), 8.26(s, 1H).
68.78% With sulfuric acid; for 4h;Reflux; Synthesis of compound 74.2. To a solution of compound 74.1 (lOg, 0.0584mol, l .Oeq.) in ethanol (100 mL) was added drop wise H2SO4 (2mL). Reaction was stirred for 4 hours at reflux temperature. After completion of the reaction, solvent was evaporated and water was added. Mixture was extracted using ethyl acetate (150ml x2). Organic layer was washed with saturated sodium bicarbonate solution (70ml x 2), dried over sodium sulfate and concentrated under reduced pressure at 45C to afford compound 74.2 (8g, 68.78%). MS (ES): m/z 200.4 [M+H] +

  • 3
  • [ 67442-07-3 ]
  • [ 39891-13-9 ]
  • 1-chloro-3-(6-chloropyridin-3-yl)propan-2-one [ No CAS ]
 

Historical Records

Technical Information

Categories

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[ 39891-13-9 ]

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