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Structure of 101623-69-2

Chemical Structure| 101623-69-2

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Product Details of [ 101623-69-2 ]

CAS No. :101623-69-2
Formula : C9H8ClNO5
M.W : 245.62
SMILES Code : O=C(OC(Cl)C)OC1=CC=C([N+]([O-])=O)C=C1
MDL No. :MFCD19441847
InChI Key :DXVQFTPXVZUWIF-UHFFFAOYSA-N
Pubchem ID :10538354

Safety of [ 101623-69-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 101623-69-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 16
Num. arom. heavy atoms 6
Fraction Csp3 0.22
Num. rotatable bonds 5
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 57.84
TPSA ?

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

81.35 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.78
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

3.02
Log Po/w (WLOGP)?

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

2.7
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.

1.05
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

-0.16
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.68

Water Solubility

Log S (ESOL):?

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

-3.21
Solubility 0.15 mg/ml ; 0.000612 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.

-4.39
Solubility 0.00993 mg/ml ; 0.0000404 mol/l
Class?

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

Moderately 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

-2.27
Solubility 1.33 mg/ml ; 0.00543 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

No
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

Yes
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.

-5.65 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

4.0 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)

2.8

Application In Synthesis of [ 101623-69-2 ]

* 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.

  • Upstream synthesis route of [ 101623-69-2 ]

[ 101623-69-2 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 100-02-7 ]
  • [ 50893-53-3 ]
  • [ 101623-69-2 ]
YieldReaction ConditionsOperation in experiment
97% With pyridine In dichloromethane at 0 - 20℃; for 1.5 h; To an ice cold reaction mixture containing p-nitrophenol (1.39 g, 10 mmol) and pyridine (0.81 g, 10 mmol) in dichloromethane (60 mL) was added 1-chloroethyl chloroformate (1.2 mL, 11 mmol). The mixture was stirred at 0° C. for 30 min and then at room temperature for 1 hour. After removing the solvent under reduced pressure, the residue was dissolved in ether, washed with water, 10percent citric acid and water. The ether layer was dried over Na2SO4 and evaporated under reduced pressure to give 2.4 g (97percent) of the title compound (57) as an off-white solid. 1H NMR (CDCl3): 1.93 (d, 3H), 6.55 (q, 1H), 7.42 (d, 2H), 8.28 (d, 2H).
92% With pyridine In dichloromethane at 0 - 20℃; for 6 h; Example 3: 1-iodoethyl 4-nitrophenyl carbonateSTEP A: 1-chloroethyl 4-nitrophenyl carbonate.To a solution of 4-nitrophenol (3.0 g, 21.6 mmol) and pyridine (1.9 mL, 24 mmol) in CH2C12 (48 mL) cooled to 0°C, 1-chloroethyl chloroformate (2.3 mL, 21.6 mmol) was added. The reaction was stirred at room temperature for 5-6 hours, then washed with NaH2PC>4 (5percent) and brine, dried over Na2SC>4 and concentrated affording the title compound (4.88 g, 92percent) as a pale yellow solid.
92% at 0 - 20℃; STEP A: 1-chloroethyl 4-nitrophenyl carbonateTo a solution of 4-nitrophenol (3.0 g, 21.6 mmol) and pyridine (1.9 mL, 24 mmol) cooled to 0°C, 1-chloroethyl chloroformate (2.3 mL, 21.6 mmol) was added. The reaction was stirred at room temperature for 5-6 hours, then washed with Na3/4P04 (5percent) and brine, dried over Na2 S C>4 and concentrated affording the title compound (4.88 g, 92percent) as a pale yellow solid.1H-NMR (CDC13) : 8.32 (2H,m); 7.44 (2H,m); 6.52 ( 1H, q, J=5.8 Hz); 1.94 (3H, d, J=5.5Hz) .
88% With pyridine In chloroform at 0 - 20℃; Step 1:
1-Chloroethylchloroformate (7.8 ml, 72 mmol, 1 eq.) was added to an ice-cold solution of p-nitrophenol (10 g, 72 mmol) in chloroform (100 mL), followed by drop wise addition of pyridine (8.8 ml, 108 mmol, 1.5 eq.) over a period of 20 min.
The mixture was stirred in the ice-cold bath for 15 min, and then at room temperature overnight.
The reaction mixture was sequentially washed with water, 1 N hydrochloric acid, water, 1 N sodium hydroxide, water, and brine.
The organic phase was dried over Na2SO4, and concentrated to give yellow oil which, upon standing, crystallized to afford the corresponding chloroethyl carbonate (15.5 g, 88percent).
85% With triethylamine In dichloromethane at 0 - 20℃; To an ice-cold solution of 4-nitrophenol (2.0 g, 15 mmol) and triethylamine (1.6 g, 16 mmol) in dichloromethane (20 ml) was added a solution of 1-chloroethyl chloroformate (2.1 g, 19 mmol) in dichloromethane, and the mixture was stirred for 15 min at 0 °C and then overnight at room temperature. The mixture was extracted with dichloromethane (50 ml), washed successively with water (50 ml), 0.5 N sodium hydroxide (50 ml), saturated aqueous sodium chloride solution (50 ml), and water (3 x 50 ml), and dried over Na2SO4. The dichloromethane solution was filtered and evaporated under reduced pressure, and the residue was purified by silica gel column chromatography with chloroform (100percent) as eluent to furnish pure 1-chloroethyl 4- nitrophenyl carbonate, as a white solid in 85percent yield.

References: [1] Journal of Antibiotics, 1999, vol. 52, # 7, p. 643 - 648.
[2] Patent: US2006/229361, 2006, A1, . Location in patent: Page/Page column 37.
[3] Journal of Pharmacology and Experimental Therapeutics, 2016, vol. 357, # 2, p. 240 - 247.
[4] Journal of Medicinal Chemistry, 1988, vol. 31, # 2, p. 318 - 322.
[5] Patent: WO2011/92065, 2011, A1, . Location in patent: Page/Page column 60.
[6] Patent: WO2011/101245, 2011, A1, . Location in patent: Page/Page column 38.
[7] Bioorganic and Medicinal Chemistry Letters, 1997, vol. 7, # 14, p. 1811 - 1816.
[8] Patent: US2008/146642, 2008, A1, . Location in patent: Page/Page column 45.
[9] Patent: WO2007/27248, 2007, A2, . Location in patent: Page/Page column 22.
[10] Bioorganic and Medicinal Chemistry, 2001, vol. 9, # 1, p. 191 - 198.
[11] Journal of Medicinal Chemistry, 2016, vol. 59, # 14, p. 6658 - 6670.
[12] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 21, p. 7593 - 7603.
[13] Journal of Medicinal Chemistry, 1999, vol. 42, # 19, p. 3994 - 4000.
[14] Patent: US2002/19437, 2002, A1, .
[15] Patent: US5602118, 1997, A, .
[16] Patent: US2004/138108, 2004, A1, .
[17] Patent: WO2008/79839, 2008, A1, . Location in patent: Page/Page column 40.
[18] Patent: WO2010/63002, 2010, A2, . Location in patent: Page/Page column 26.
 

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