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Chemical Structure| 83823-06-7

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Product Details of [ 83823-06-7 ]

CAS No. :83823-06-7
Formula : C10H7ClO3
M.W : 210.61
SMILES Code : O=C(C(CO1)=CC2=C1C=CC(Cl)=C2)O
MDL No. :MFCD00052362
InChI Key :ZRCGKWSNRRTAJY-UHFFFAOYSA-N
Pubchem ID :596929

Safety of [ 83823-06-7 ]

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

Computational Chemistry of [ 83823-06-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 6
Fraction Csp3 0.1
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 52.5
TPSA ?

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

46.53 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.8
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

2.13
Log Po/w (WLOGP)?

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

2.09
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.

1.75
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

2.28
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.01

Water Solubility

Log S (ESOL):?

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

-2.74
Solubility 0.384 mg/ml ; 0.00182 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.

-2.74
Solubility 0.384 mg/ml ; 0.00183 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

-2.71
Solubility 0.406 mg/ml ; 0.00193 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.

-6.07 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.

0.56

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

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)

2.68

Application In Synthesis of [ 83823-06-7 ]

* 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 [ 83823-06-7 ]

[ 83823-06-7 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 57543-67-6 ]
  • [ 83823-06-7 ]
YieldReaction ConditionsOperation in experiment
65%
Stage #1: With sodium hydroxide In tetrahydrofuran; water for 4 h; Heating / reflux
Stage #2: With hydrogenchloride In tetrahydrofuran; water
5-chloro-2-hydroxy-benzaldehyde Compound 15a (10.0 mmol, 1.7 g), acrylonitrile(50.0 mmol, 2.14 mL) and DABCO (2.33 mmol, 0.26 g) were mixed together and heated toreflux overnight using an oil bath. After the flask was cooled to room temperature, Et2O (100mL) was added and the Et2O layer was washed with 10percent NaOH solution followed by IN HCland brine. The organic layer was dried over MgSO4, filtered and the solvent was removed invacuo to obtain 6-chloro-2H-chromene-3-carbonitrile Compound 15b as a yellow solid (1.42 g,74percent), which was used in the next step without further purification (the preceding was describedin Wise, L. et al. J. Med. Chem., 1988, 31, 688).; THF (2 mL) and 10percent NaOH solution (100 mL) was added to a round bottom flaskcontaining Compound 15b (7.43 mmol, 1.42 g). The solution was heated to reflux for 4 hrs.The flask was immersed in an ice-bath and the solution was acidified by careful addition ofcone. HCl. The resulting pale yellow solid was filtered and dried in a vacuum oven to obtain 6-chloro-2H-chromene-3-carboxylic acid Compound 15c (1.02 g, 65percent).; Sodium triacetoxyborohydride (3.5 mmol, 0.75 g) was added to a mixture of 4-nitro-fnmnmitirl tlf\\ O K mmnl fl 47 cA ('9.<\\^-hirl\\/f Inf? 7 nhpnt-9-vlaminp <~.rmnminrl15d (3.0 mmol, 0.33 g) and glacial acetic acid (3 drops) in CH2C12 (40 mL). The resultingsuspension was allowed to stir at room temperature for 12 hrs. An aliquot of the reactionmixture showed the formation of product (MS m/e 247,100percent). An aqueous solution offormaldehyde (37percent solution, 9.6 mmol, 0.8 mL) was added to the reaction mixture followed bysodium triacetoxyborohydride (3.5 mmol, 0.75 g) and the mixture was allowed to stir at r.t. for2 hrs. The reaction mixture was basified with 2N NaOH solution and was extracted withCH2C12. The organic layer was washed with brine, separated and dried over Na2SO4. Thedrying agent was filtered and the solvent was removed in vacua to obtain (25)-bicyclo[2.2,l]hept-2-yl-methyl-(4-nitro-benzyl)-amine Compound 15e (0.72 g, 98percent) as anorange oil. MS m/e 261 (M+H, 100percent), which was used in the next step without furtherpurification.; SnCl2.2H2O (10.4 mmol, 2.35 g) was added to a solution of Compound 15e (2.76mmol, 0.72 g) in EtOH (25 mL) at r.t. The resulting yellow solution was stirred for 2 days.The solvent was removed in vacua and the resulting residue was basified with 2N NaOHsolution and the aqueous layer was extracted with CH2C12 (2 X 30 mL). The combined organiclayers were dried over Na2SC>4, filtered and the solvent was removed in vacuo to obtain (25)-(4-amino-benzyl)-bicyclo[2.2.1]hept-2-yl-methyl-amine Compound 15f (0.54 g, 85percent yield) as athick yellow oil. MS m/e 231 (M+H, 100percent), which was used in the next step without furtherpurification.; EDCI (0.33 mmol, 0.07 g) was added in one portion to a suspension of Compound 15f(0.24 mmol, 0.06 g), 6-ch]oro-2H-chromene-3-carboxylic acid Compound 15g (0.22 mmol,0.04 g) and HO'Bt (0.22 mmol, 0.03 g) in DMF (5,0 mL) at 0°C. The resulting suspension waswarmed to r.t. and then a crystal of DMAP and Et3N (0.65 mmol, 0.1 mL) was added and thereaction mixture was stirred overnight. The orange-yellow suspension was poured in water andwas extracted with EtOAc (25 mL). The organic layer was washed with water (2 X 20 mL)followed by 5percent NaOH solution (10 rnL) and brine. The organic layer was separated, driedover NajSCM and filtered. The solvent was removed iirvacuo and the resulting residue wast ''purified by preparative TLC (15:1 CH2Cl2/MeOH) to yield 6-chloro-2H-chromene-3-carboxylicacid (2>S)-{4-[(bicyclo[2.2.1]hept-2-yl-methyl-amino)-methyl]-phenyl}-amide Compound ISh(0.06 g, 61percent) as a pale yellow solid. MS m/e 423 (M+H, 100percent).; lodomethane (0.5 mL) was added to a solution of Compound 15h (0.08 mmol, 0,03 g)in CH2C12 (1.0 mL) at r.t. and the resulting solution was allowed to stand overnight. A yellowprecipitate was observed and the solvent was removed in vacua. The resulting yellow solidwas washed with Et2O to obtain Compound 110 (0.05 g, 96percent) as a yellow solid. MS m/e 437(M+H, 100percent).
65%
Stage #1: With sodium hydroxide; water In tetrahydrofuran for 4 h; Heating / reflux
Stage #2: With hydrogenchloride; water In tetrahydrofuran
THF (2 mL) and 10percent NaOH solution (100 mL) was added to a round bottom flask containing Compound 15b (7.43 mmol, 1.42 g). The solution was heated to reflux for 4 hrs. The flask was immersed in an ice-bath and the solution was acidified by careful addition of conc. HCl. The resulting pale yellow solid was filtered and dried in a vacuum oven to obtain 6-chloro-2H-chromene-3-carboxylic acid Compound 15c (1.02 g, 65percent).
References: [1] Archiv der Pharmazie, 2012, vol. 345, # 10, p. 767 - 770.
[2] Patent: WO2006/12135, 2006, A1, . Location in patent: Page/Page column 75-77.
[3] Patent: US2006/293379, 2006, A1, . Location in patent: Page/Page column 81.
[4] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1982, vol. 21, # 4, p. 344 - 347.
[5] RSC Advances, 2014, vol. 4, # 102, p. 58397 - 58403.
[6] Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 7, p. 1382 - 1390.
  • 2
  • [ 1215266-96-8 ]
  • [ 83823-06-7 ]
YieldReaction ConditionsOperation in experiment
87.4% With potassium hydroxide In water for 42 h; Reflux General procedure: General procedure for synthesis of the chromene-3-carboxylic acids 10a-e
The general procedure for preparation of the chromene-3-carboxylic acids 10a-e is illustrated by the following example.
A stirred mixture of the Baylis-Hillman adduct 7b (1.0 mmol) and KOH (4.0 mmol) in water (4 mL) was heated under reflux for 42 h.
After cooling to room temperature, the reaction mixture was acidified with 2 M-HCl.
The resulting precipitate was filtered off, washed and dried to afford 6-bromo-2H-chromene-3-carboxylic acid 10b.
3.4.2
6-Chloro-2H-chromene-3-carboxylic acid 10c
6-Chloro-2H-chromene-3-carboxylic acid 10c as a yellow solid (185 mg, 87.4percent), mp 242-243 °C (lit.
14
240.1-241.2 °C); 1H NMR (600 MHz; DMSO-d6): δ 4.94 (2H, s), 6.88 (1H, d, J=8.6 Hz), 7.29 (1H, d, J=8.6 Hz), 7.44 (1H, s), 7.46 (1H, s) and 12.98 (1H, br s); 13C NMR (150 MHz; DMSO-d6): δ 64.4, 117.4, 122.5, 124.8, 125.2, 128.2, 131.0, 131.1, 153.1 and 165.3.
References: [1] Tetrahedron, 2015, vol. 71, # 29, p. 4868 - 4873.
  • 3
  • [ 635-93-8 ]
  • [ 83823-06-7 ]
References: [1] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1982, vol. 21, # 4, p. 344 - 347.
[2] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1982, vol. 21, # 4, p. 344 - 347.
[3] Archiv der Pharmazie, 2012, vol. 345, # 10, p. 767 - 770.
[4] RSC Advances, 2014, vol. 4, # 102, p. 58397 - 58403.
[5] Bioorganic and Medicinal Chemistry, 2019, vol. 27, # 7, p. 1382 - 1390.
  • 4
  • [ 57544-34-0 ]
  • [ 83823-06-7 ]
References: [1] Tetrahedron: Asymmetry, 1995, vol. 6, # 4, p. 1001 - 1012.
  • 5
  • [ 83823-19-2 ]
  • [ 83823-06-7 ]
References: [1] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1982, vol. 21, # 4, p. 344 - 347.
 

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