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Structure of 7212-28-4

Chemical Structure| 7212-28-4

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Product Details of [ 7212-28-4 ]

CAS No. :7212-28-4
Formula : C8H8INO
M.W : 261.06
SMILES Code : O=C(NC1=CC=CC=C1)CI
MDL No. :MFCD16170501
InChI Key :YXNAWCUIZOCJNG-UHFFFAOYSA-N
Pubchem ID :11207703

Safety of [ 7212-28-4 ]

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

Computational Chemistry of [ 7212-28-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 3
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 53.72
TPSA ?

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

29.1 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

1.82
Log Po/w (WLOGP)?

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

1.87
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.

2.15
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

2.2
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.91

Water Solubility

Log S (ESOL):?

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

-2.81
Solubility 0.404 mg/ml ; 0.00155 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.

-2.05
Solubility 2.32 mg/ml ; 0.00889 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

-3.75
Solubility 0.0459 mg/ml ; 0.000176 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.

-6.6 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

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<0.0
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)

1.54

Application In Synthesis of [ 7212-28-4 ]

* 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.

  • Upstream synthesis route of [ 7212-28-4 ]
  • Downstream synthetic route of [ 7212-28-4 ]

[ 7212-28-4 ] Synthesis Path-Upstream   1~6

  • 1
  • [ 587-65-5 ]
  • [ 7212-28-4 ]
YieldReaction ConditionsOperation in experiment
90% With potassium iodide In acetone at 80℃; Add 33.33 ml of acetone to the flask at 80° C. and condense reflux.Addition of 0.0135 mol of N-phenyl 2-chloroacetamide, followed by 0.0225 mol of potassium iodide,Determine whether the reaction is over by TCL. After the reaction is completed, add 50ml of water.Another 100 ml of ethyl acetate was added, the organic phase was extracted by extraction, and the organic phase was washed with 50 ml of saturated saline.Anhydrous sodium sulfate was dried and distilled under reduced pressure to give a crude product, which was recrystallized from ethyl acetate to give a white solid.Yield 90percent;
90% With potassium iodide In acetone at 80℃; Add 33.33 ml of acetone to the flask at 80° C. and condense reflux.Addition of 0.0135 mol of N-phenyl 2-chloroacetamide, followed by 0.0225 mol of potassium iodide,Determine whether the reaction is over by TCL. After the reaction is completed, add 50ml of water.Another 100 ml of ethyl acetate was added, the organic phase was extracted by extraction, and the organic phase was washed with 50 ml of saturated saline.Anhydrous sodium sulfate was dried and distilled under reduced pressure to give a crude product, which was recrystallized from ethyl acetate to give a white solid.Yield 90percent;
84.5% With potassium iodide In acetone at 60℃; for 2 h; General procedure: A mixture of 5a-j (18 mmol) and KI (4.4 g, 27 mmol) inacetone (40 mL) was refluxed for 2 h, and the solvent was evaporated in vacuo. Water was added, and the solids were collected and dried to give compounds 6a-j. 1.5.1. 2-Iodo-N-phenylacetamide (6a) The title compound was obtained in 84.5percent yield as a whitesolid: mp 144–146 °C; 1H NMR (300 MHz, CDCl3) δ 3.86 (s,2H, ICH2), 7.15 (t, J =7.4 Hz, 1H, ArH), 7.35 (t, J = 7.8Hz, 2H, ArH), 7.50 (d, J = 7.9 Hz,2H, ArH), 7.69 (s, 1H, NH); ESI calcd. 262.0 [M + H]+, found 262.0[M + H]+.
71% With potassium iodide In acetone for 9.5 h; Reflux To a solution of 2-chloro-N-phenylacetamide (1.08 g,6.36 mmol) in dry acetone (30 mL) was added powdered KI (5.08 g, 30.6 mmol). The mixturewas heated at reflux for 9.5 h, and the reaction mixture was then filtered. Purification by silicagel column chromatography (hexane/EtOAc (3:1)) followed by recrystallization fromTHF/hexane afforded IPAA as a white solid (1.17 g, 71percent).

References: [1] Patent: CN107880037, 2018, A, . Location in patent: Paragraph 0010.
[2] Patent: CN107880036, 2018, A, . Location in patent: Paragraph 0011.
[3] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 4, p. 1360 - 1364.
[4] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2014, vol. 53, # 6, p. 733 - 739.
[5] Archiv der Pharmazie, 2008, vol. 341, # 11, p. 690 - 695.
[6] Chemistry Letters, 2015, vol. 44, # 10, p. 1374 - 1376.
[7] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 15, p. 5008 - 5012.
  • 2
  • [ 75-11-6 ]
  • [ 103-71-9 ]
  • [ 7212-28-4 ]
YieldReaction ConditionsOperation in experiment
96% With methyllithium; lithium bromide In diethyl ether at -78℃; for 0.5 h; General procedure: To a cooled (–78°C) solution of isocyanate (1.0 equiv) in dry Et2O (1 M concentration) was added the dihalomethane derivative (1.5 equiv). After 2 min, an ethereal solution of 1.5 M MeLi–LiBr (1.25equiv) was added dropwise over 5 min. The resulting solution was stirred for the appropriate time (see Table 1 and Scheme 2) at that temperature. Sat. aq NH4Cl was added (2 mL/mmol substrate) and the cooling bath was removed, the mixture was stirred till it reached r.t., and then it was extracted with additional Et2O (2 × 5 mL) and washed with water (5 mL) and brine (10 mL). The organic phase was dried (anhyd Na2SO4), filtered, and the solvent removed under reduced pressure to give pure samples of haloacetamides.
References: [1] Chemical Communications, 2013, vol. 49, # 75, p. 8383 - 8385.
[2] Synthesis (Germany), 2014, vol. 46, # 21, p. 2897 - 2909.
  • 3
  • [ 615-43-0 ]
  • [ 75-36-5 ]
  • [ 7212-28-4 ]
YieldReaction ConditionsOperation in experiment
68% With sodium hydroxide In tetrahydrofuran; water at 0 - 20℃; Acetyl chloride (6 mmol) was added dropwise to the mixture of 2-iodoaniline (5 mmol) and sodium hydroxide (13 mmol) in THF/H2O (1/1, 4 mL). Stirred the mixture at 0° C. for 2 h, and then at room temperature for overnight. The mixture was diluted with 10 mL water and extracted with diethyl ether 3 times. The combined organic layer was washed with water 3 times and brine. Dried over sodium sulfate, filtered, and removed solvent. The residue was then purified by column chromatography afforded white solid of 2-iodoacetanilide 68percent yield. NMR
References: [1] Patent: US7473786, 2009, B1, . Location in patent: Page/Page column 24.
  • 4
  • [ 64-69-7 ]
  • [ 62-53-3 ]
  • [ 7212-28-4 ]
References: [1] Journal of Biological Chemistry, 2017, vol. 292, # 27, p. 11230 - 11242.
  • 5
  • [ 62-53-3 ]
  • [ 7212-28-4 ]
References: [1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 15, p. 5008 - 5012.
[2] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2014, vol. 53, # 6, p. 733 - 739.
[3] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 4, p. 1360 - 1364.
[4] Patent: CN107880037, 2018, A, .
[5] Patent: CN107880036, 2018, A, .
  • 6
  • [ 38020-81-4 ]
  • [ 62-53-3 ]
  • [ 7212-28-4 ]
References: [1] Yakugaku Zasshi, 1934, vol. 54, p. 25,40, 41[2] Proceedings of the Imperial Academy (Tokyo), 1933, vol. 9, p. 599.
 

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