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Structure of 1201924-32-4

Chemical Structure| 1201924-32-4

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Product Details of [ 1201924-32-4 ]

CAS No. :1201924-32-4
Formula : C7H6ClNO2
M.W : 171.58
SMILES Code : O=C(O)C1=NC(Cl)=CC=C1C
MDL No. :MFCD16249840
InChI Key :ODSPBBWQVLWOPG-UHFFFAOYSA-N
Pubchem ID :46941470

Safety of [ 1201924-32-4 ]

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

Computational Chemistry of [ 1201924-32-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 41.17
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.

1.17
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

2.04
Log Po/w (WLOGP)?

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

1.74
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.

-0.18
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

1.82
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.32

Water Solubility

Log S (ESOL):?

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

-2.53
Solubility 0.51 mg/ml ; 0.00297 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.

-2.72
Solubility 0.325 mg/ml ; 0.0019 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

-2.4
Solubility 0.688 mg/ml ; 0.00401 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.

-5.9 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)

1.64

Application In Synthesis of [ 1201924-32-4 ]

* 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 [ 1201924-32-4 ]

[ 1201924-32-4 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 1201924-32-4 ]
  • [ 18107-18-1 ]
  • [ 878207-92-2 ]
YieldReaction ConditionsOperation in experiment
With methanol; In tetrahydrofuran; at 20℃; for 2h; Step 4. Methyl 6-chloro-3 -methylpyridine-2-carbox ylate6-Chloro-3-methylpyridine-2-carboxylic acid (3.69 g, 21.51 mmol) was taken up in THF (100 raL)/MeOH (25 mL). A solution of TMS-diazomethane (21.5 mL, 43.0 mmol) was added and the resulting solution stirred at room temperature for 2 hours. The solvent was removed in vacuo and the residue purified by silica gel chromatography (2-20% EtOAc/hexanes) to give the title compound as a white solid.LRMS (APCI) calc'd for (C8H9ClNO2) [M+Hf: 186, 188, Found: 186, 188.
  • 2
  • [ 1201924-31-3 ]
  • [ 1201924-32-4 ]
YieldReaction ConditionsOperation in experiment
Step 3. 6-Chloro-3 -methylpyridine-2-carboxylic acid6-Chloro-3-methylrhoyridine-2-carbonitrile (2.95 g, 19.3 mmol) and Potassium hydroxide (3.25 g, 58 mmol) were stirred in refluxing water (60 mL) for 2 hours. The mixture was cooled to room temperature, 30 mL of 2 N HCl was added, followed by the addition of water. The resulting mixture was extracted with EtOAc (3x). The combined organic extracts were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo to give the title compound as a white solid.1H NMR (600 MHz, DMSO): delta 13.45 (br s, 1 H), 7.81 (d, J= 8.4 Hz5 1 H), 7.55 (d, J- 8.4 Hz, 1 H), 2.39 (s, 3 H).
  • 3
  • [ 1201924-32-4 ]
  • [ 3095-48-5 ]
  • [ 1529761-13-4 ]
YieldReaction ConditionsOperation in experiment
76% Scheme 14. step B. To a solution of6-chloro-3-methyl-pyridine-2-carboxylic acid(0.35 g, 0.20 mmol) in CH2Ch (6 ml) at room temperature are added methyl3-amino-3,5-dimethylbenzoate (0.36 g, 0.20 mmol, see preparation 12), and N,N-diisopropylethylamine (0.77 g, 0.60 mmol). After stirring the reaction mixture for 10minutes, 1-propanephosphonic acid cyclic anhydride (50percent solution in ethyl acetate, 2.54g, 0.80 mmol) is added via syringe. After 16 hours at ambient temperature, the reactionmixture is diluted with CH2Ch, washed with water and brine. The organic layers arecombined and dried over anhydrous Na2S04, filtered, and concentrated under reduced pressure to give the title compound as a white powder (0.52 g, 76 percent). Mass spectrum15(m/z): 333.2 (M+ 1).
  • 4
  • [ 1201924-32-4 ]
  • [ 3095-48-5 ]
  • [ 1529760-72-2 ]
YieldReaction ConditionsOperation in experiment
81% Scheme 15, step A. To a solution of 6-chloro-3-methyl-pyridine-2-carboxylicacid (0.70 g, 4.093 mmol, see preparation 1) in CH2Ch (6 mL) at 0 oc are added <strong>[3095-48-5]methyl 4-amino-3,5-dimethylbenzoate</strong> (0.74 g, 4.093 mmol, see preparation 12), andtriethylamine (0.83 g, 8.187 mmol). After stirring the reaction mixture for 10 minutes, 1-propanephosphonic acid cyclic anhydride (50percent solution in ethyl acetate, 2.60 g, 8.187mmol) is added via syringe and stirred at ambient temperature. After 12 hours, the solvent is removed under reduced pressure and the residue is diluted with water andextracted with ethyl acetate. The organic layers are combined and dried over anhydrousNa2S04, filtered, and concentrated under reduced pressure. The resulting residue ispurified by flash chromatography (silica gel) using a gradient of0-40percent ethyl acetate inhexanes to give the title compound as an off-white solid (1.10 g, 81 percent). Mass spectrum (m/z): 333.2 (M+ 1).
  • 5
  • [ 878207-92-2 ]
  • [ 1201924-32-4 ]
YieldReaction ConditionsOperation in experiment
97% With water; sodium hydroxide; In tetrahydrofuran; at 0 - 50℃; for 2h; A solution of aqueous 2N NaOH (5 ml) is added to a stirred solution of <strong>[878207-92-2]methyl 6-chloro-3-methyl-pyridine-2-carboxylate</strong> (0.500 g, 2.702 mmol) in THF (10 mL) at 0 C. The mixture is heated at 50C for 2 hours. The reaction mixture is acidified with aqueous citric acid solution and extracted with EtOAc (2 x 10 ml). The combined organic layers are dried over sodium sulfate, filtered, and concentrated under reduced pressure to give the title compound as an off-white solid (0.45 g, 97%). The residue is used in next step without further purification. Mass spectrum (m/z): 172.0 (M+H)+.
84% With water; sodium hydroxide; In tetrahydrofuran; methanol; at 20℃; for 3h; Scheme 1, step A. A solution of aqueous IN NaOH (10 ml) is added to a stirred solution ofmethyl6-chloro-3-methyl-pyridine-2-carboxylate (1.0 g, 5.39 mmoles) inTHF:MeOH (IOml:2 ml). The mixture is stirred at room temperature for 3 hours. Theorganic solvent is removed under reduced pressure and the semi-solid is dissolved inwater and acidified to pH I-2 with aqueous IN HCI. The resulting precipitate is filtered,washed with water, and dried at 40C in a vacuum oven for I2 hours to give the title compound as a white solid (780 mg, 84%). Mass spectrum (m/z): I72.0 (M+I).
  • 6
  • [ 59718-84-2 ]
  • [ 1201924-32-4 ]
  • 7
  • [ 67-56-1 ]
  • [ 1201924-32-4 ]
  • [ 878207-92-2 ]
YieldReaction ConditionsOperation in experiment
97% With thionyl chloride; at 65℃; for 3h; Step A: Methyl 6-chloro-3-methylpicolinate. Thionyl chloride (208 g, 1.75 mol) was added to a solution of 6-chloro-3-methylpicolinic acid (200 g, 1.17 mol) in methanol (300 mL) and the reaction mixture was warmed to 65 C. After 3 hours, the reaction mixture was concentrated under reduced pressure, and saturated aqueous NaHCO3 solution (1 L) was added. The aqueous layer was extracted twice with ethyl acetate which resulted in several organic solvent fractions which were combined, dried over Na2SO4, filtered, and concentrated to dryness under reduced pressure to provide the title compound as a dark-brown solid (210 g, 97%). 1H NMR (400 MHz, CDCl3) 7.57 (d, J=8.0 Hz, 1H) 7.36 (d, J=8.0 Hz, 1H) 3.95 (s, 3H) 2.53 (s, 3H).
 

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Technical Information

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