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Structure of 90942-47-5

Chemical Structure| 90942-47-5

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Product Details of [ 90942-47-5 ]

CAS No. :90942-47-5
Formula : C9H11Cl2NO2
M.W : 236.10
SMILES Code : Cl.COC(=O)C1=C(Cl)C=CC(CN)=C1
MDL No. :MFCD16876981
Boiling Point : No data available
InChI Key :RVCZOTOWWCOGCQ-UHFFFAOYSA-N
Pubchem ID :66524840

Safety of [ 90942-47-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302+H312+H332-H315-H319-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 90942-47-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 57.37
TPSA ?

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

52.32 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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.

2.24
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.

2.23
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

1.96
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.69

Water Solubility

Log S (ESOL):?

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

-2.71
Solubility 0.462 mg/ml ; 0.00196 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.

-2.77
Solubility 0.404 mg/ml ; 0.00171 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

-3.14
Solubility 0.171 mg/ml ; 0.000724 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.

-6.29 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

0.0 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)

1.77

Application In Synthesis of [ 90942-47-5 ]

* 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 [ 90942-47-5 ]

[ 90942-47-5 ] Synthesis Path-Downstream   1~15

  • 2
  • [ 90942-47-5 ]
  • [ 1381846-21-4 ]
  • 3
  • [ 90942-47-5 ]
  • [ 3282-30-2 ]
  • [ 1381846-41-8 ]
YieldReaction ConditionsOperation in experiment
Preparation 24Methyl 2-chloro-5-[(2,2-dimethylpropanoylamino)methyl]benzoateTo a thermally controlled reactor, add <strong>[90942-47-5]methyl 5-(aminomethyl)-2-chlorobenzoate hydrochloride</strong> (700 g, 3.51 mol, 1.0 equiv), dichloromethane (4.9 L), and N,N-diisopropylethylamine (1.71 L, 9.82 mol, 2.8 equiv). Add pivaloyl chloride (515 mL, 4.21 mol, 1.2 equiv) dropwise at such a rate that the internal temperature does not exceed 21 C. Upon completion of the addition, stir the reaction mixture at room temperature for one hour. Quench the reaction mixture with saturated aqueous sodium bicarbonate (10 L). Extract the mixture with dichloromethane (2×1 L), combine the organic extracts, dry over sodium sulfate, filter, and concentrate under reduced pressure to give an oil, (1.1 kg) carried on crude without further purification. MS (m/z) (35C1/37C1) 284/286 (M+1)
2 g With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 26℃; for 1.0h; To a solution of <strong>[90942-47-5]methyl 5-(aminomethyl)-2-chlorobenzoate hydrochloride</strong> (1.80 g, 6.00 mmol) in CH2C12 were added DIPEA (3.096 g, 2.4 mmol ) followed by pivaloyl chloride (1.2 mL, 9.0 mmol) at 0-5C and the reaction mixture was stirred at rt for lh before it was quenched with water and was extracted with chloroform. The organic layer was separated, dried, filtered and concentrated to afford 2.0 g of the title product. 1H NMR (300 MHz, DMSO d6): delta 8.16 (m, 1H), 7.65 (s, 1H), 7.53 (d, / = 8.4 Hz, 1H), 7.41 (d, / = 8.4 Hz, 1H), 4.25 (d, / = 5.7 Hz, 2H), 3.85 (s, 3H), 1.15 (s, 9H).
2 g With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 22 - 26℃; for 2.0h; General procedure: To a solution of ethyl 3-(aminomethyl)-6-chloro-2-fluorobenzoate (70 mg, 0.3 mmol) in THF (3 mL) were added Et3N (0.105 mL, 0.76 mmol) and pivaloyl chloride (38 muL, 0.31 mmol). The reaction mass was stirred at rt for 2 h, diluted with EtOAc and was washed with water, and brine. The organic layer was separated, dried, filtered and concentrated to afford 70 mg of the title product. 1H NMR (300 MHz, DMSO-d6): delta 8.15 (br t, 1H), 7.43-7.35 (m, 2H), 4.38 (q, J=7.2 Hz, 2H), 4.26 (d, J=5.7 Hz, 2H), 1.30 (t, J=6.9 Hz, 3H), 1.11 (s, 9H). 10301] The title compound was prepared following the procedure described in step-2 of Intermediate-2 using <strong>[90942-47-5]methyl 5-(aminomethyl)-2-chlorobenzoate hydrochloride</strong> (1.80 g,6.00 mmol), DIPEA (3.096 g, 2.4 mmol) and pivaloyl chloride (1.2 mE, 9.0 mmol) in THF (20 mE) to afford 2.0 g of the title product. 1H NMR (300 MHz, DMSO d5): 8.16 (m, 1H), 7.65 (s, 1H), 7.53 (d, J=8.4 Hz, 1H), 7.41 (d, J=8.4 Hz, 1H),4.25 (d, J=5.7 Hz, 2H), 3.85 (s, 3H), 1.15 (s, 9H).
2 g With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃; for 2.0h; To a solution of <strong>[90942-47-5]methyl 5-(aminomethyl)-2-chlorobenzoate hydrochloride</strong> (1.80 g, 6.00 mmol) in THF (20 mL) were added DIPEA (3.096 g, 24.0 mmol) and pivaloyl chloride (1.2 mL, 9.0 mmol). The reaction mass was stirred at rt for 2 h, diluted with EtOAc and was washed with water, and brine. The organic layer was separated, dried, filtered and concentrated to afford 2.0 g of the title product. 1H NMR (300 MHz, DMSO-i): delta 8.16 (m, 1H), 7.65 (s, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.41 (d, J = 8.4 Hz, 1H), 4.25 (d, J = 5.7 Hz, 2H), 3.85 (s, 3H), 1.15 (s, 9H).

  • 7
  • [ 90434-27-8 ]
  • [ 90942-47-5 ]
  • 8
  • [ 1427158-17-5 ]
  • [ 90942-47-5 ]
YieldReaction ConditionsOperation in experiment
80 mg With dihydrogen peroxide; In water; ethyl acetate; at 22 - 26℃; for 2.0h; A solution of methyl 5-(((ierf-butoxycarbonyl)amino)methyl)-2-chlorobenzoate (100 mg, 0.334 mmol) in EtOAc saturated with HC1 solution (1 mL) was stirred at rt for 2 h. The reaction mixture was concentrated and was triturated with pentane to afford 80 mg of the title product. H NMR (300 MHz, DMSO d6): delta 8.20 (br s, 3H), 7.95 (s, 1H), 7.67 (s, 2H), 4.00 (s, 2H), 3.88 (s, 3H).
80 mg With hydrogenchloride; In ethyl acetate; at 22 - 26℃; for 2.0h; A solution of methyl 5-(((iert-butoxycarbonyl)amino)methyl)-2-chlorobenzoate (100 mg, 0.334 mmol) in EtOAc saturated with HC1 (1 mL) was stirred at rt for 2 h. The reaction mixture was concentrated and was triturated with pentane to afford 80 mg of the title product. 1H NMR (300 MHz, DMSO d6): delta 8.20 (br s, 3H), 7.95 (s, 1H), 7.67 (s, 2H), 4.00 (s, 2H), 3.88(s, 3H).
80 mg With hydrogenchloride; In ethyl acetate; at 22 - 26℃; for 2.0h; A solution of methyl 5-(((tert-butoxycarbonyl)amino)methyl)-2-chlorobenzoate (100 mg, 0.334 mmol) in EtOAc saturated with HCl (1 mL) was stirred at rt for 2 h. The reaction mixture was concentrated and was triturated with pentane to afford 80 mg of the title product. 1H NMR (300 MHz, DMSO d6): delta 8.20 (br s, 3H), 7.95 (s, 1H), 7.67 (s, 2H), 4.00 (s, 2H), 3.88 (s, 3H).
80 mg With hydrogenchloride; In ethyl acetate; at 20℃; for 2.0h; A solution of methyl 5-(((ieri-butoxycarbonyl)amino)methyl)-2-chlorobenzoate (100 mg, 0.334 mmol) in EtOAc saturated with HCl (1 mL) was stirred at rt for 2 h. The reaction mixture was concentrated and was triturated with pentane to afford 80 mg of the title product. 1H NMR (300 MHz, DMSO-i): delta 8.20 (br s, 3H), 7.95 (s, 1H), 7.67 (s, 2H), 4.00 (s,2H), 3.88 (s, 3H).

  • 9
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  • [ 1427158-60-8 ]
  • 10
  • [ 90942-47-5 ]
  • C18H22ClNO5 [ No CAS ]
  • 11
  • [ 90942-47-5 ]
  • [ 1427158-16-4 ]
  • 12
  • [ 16480-05-0 ]
  • [ 90942-47-5 ]
  • [ 1427158-18-6 ]
YieldReaction ConditionsOperation in experiment
250 mg With N-ethyl-N,N-diisopropylamine; In dichloromethane; at -50 - 26℃; for 2.0h; To a solution 1-methylcyclopropanecarboxylic acid (140 mg, 1.39 mmol) in dichloromethane (5.0 mL) were added oxalyl chloride (211 mg, 1.6 mmol) and a drop of DMF. The reaction mass was stirred at rt for 2 h and was added to the solution of methyl 5-(aminomethyl)-2- chlorobenzoate hydrochloride (200 mg, 0.911 mmol) and DIPEA (183 mg, 1.36 mmol) in CH2CI2 (3 mL) at -50C. The reaction mixture was stirred at rt for 2 h. The reaction mixture was quenched with water and was extracted with CHCI3. The organic layer was separated, dried and concentrated to afford 250 mg of the title product. XH NMR (300 MHz, DMSO d6): delta 8.19 (m, 1H), 7.65 (s, 1H), 7.52 (d, / = 8.1Hz, 1H), 7.41 (d, / = 8.1Hz, 1H), 4.26 (d, / = 5.7 Hz, 2H), 3.85 (s, 3H), 1.27 (s, 3H), 0.94 (m, 2H), 0.53 (m, 2H).
  • 13
  • [ 90942-47-5 ]
  • [ 79-30-1 ]
  • [ 1415090-03-7 ]
YieldReaction ConditionsOperation in experiment
250 mg With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 0 - 26℃; for 2.0h; To a solution of <strong>[90942-47-5]methyl 5-(aminomethyl)-2-chlorobenzoate hydrochloride</strong> (step-2 of intermediate-4, 200 mg, 0.911 mmol) in THF were added DIPEA (183 mg, 1.36 mmol) and 1- isobutyryl chloride (145 mg, 1.36 mmol) at 0-5C. The reaction mass was stirred at rt for 2 h before it was quenched with water and was extracted with CHCI3. The organic layer was separated, dried, filtered and concentrated to afford 250 mg of the title product. XH NMR (300 MHz, DMSO d6): delta 8.36 (m, 1H), 7.65 (s, 1H), 7.53 (d, J = 8.7 Hz, 1H), 7.41 (d, J = 6.3 Hz, 1H), 4.26 (d, / = 5.7 Hz, 2H), 3.85 (s, 3H), 2.37-2.44 (m, 1H), 1.02 (d, J = 6.0 Hz, 6H).
1.2 g With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 22 - 26℃; for 2.0h; To a solution of <strong>[90942-47-5]methyl 5-(aminomethyl)-2-chlorobenzoate hydrochloride</strong> (2.50 g,10.59 mmol) in THF (20 mL) were added DIPEA (4.78 g, 37.07 mmol) andisobutyryl chloride (1.70 g, 15.89 mmol). The reaction mass was stirred at RT for 2 h. After completion of the reaction, the reaction mixture was diluted with EtOAc, washed with water and brine, dried over Na2 SO4 and concentrated to afford 1.2 g of the desired product. ?H NIVIR (300 IVIHz, DMSO-d6): 8.35 (t, 1H), 7.66 (s, 1H),7.55-7.52 (d, J= 8.1 Hz, 1H), 7.43-7.40 (d, J 8.1 Hz, 1H), 4.26 (d, J 5.7 Hz, 2H),3.85 (s, 3H), 2.44 (m, 1H), 1.02 (d, J= 6.9 Hz, 6H); MS [M+H]: 270.12.
  • 14
  • [ 90942-47-5 ]
  • [ 1427158-38-0 ]
  • [ 1436505-18-8 ]
YieldReaction ConditionsOperation in experiment
200 mg With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 22 - 26℃; for 12.0h; A solution of (iS,5S)-3-oxabicyclo[3.1.0]hexane-l-carboxylic acid (200 mg, 1.72 mmol), <strong>[90942-47-5]methyl 5-(aminomethyl)-2-chlorobenzoate hydrochloride</strong> (Intermediate-5, step-3; 488 mg, 2.06 mmol) benzotriazole-l-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (1.91 g, 4.31 mmol), DIPEA (665 mg, 5.16 mmol) in DMF (10 mL) was stirred at rt for 12h. Then the reaction mixture was diluted with water and was extracted with EtOAc. The organic layer was washed with brine, separated, dried, filtered and concentrated. The residue was purified by column chromatography to afford 200 mg of the title product. 1H NMR (300 MHz, DMSO d6): delta 8.18 (br t, 1H, NH), 7.67 (s, 1H), 7.54-7.52 (d, / = 7.8 Hz, 1H), 7.44-7.42 (d, / = 8.1 Hz, 1H), 4.29-4.27 (d, / = 6.3 Hz, 1H), 3.86- 3.63 (m, 4H), 2.05 (m, 1H), 1.34- 1.31 (m, 1H), 0.85- 0.81 (m ,lH).
  • 15
  • [ 90942-47-5 ]
  • 2-chloro-N-(2-cyclohexyl-4,4-dimethyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-5-(pivalamidomethyl)benzamide [ No CAS ]
 

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