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Chemical Structure| 199786-58-8

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(5-Bromo-2-iodophenyl)methanol

CAS No.: 199786-58-8

4.5 *For Research Use Only !

Cat. No.: A118819 Purity: 97%

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Product Details of [ 199786-58-8 ]

CAS No. :199786-58-8
Formula : C7H6BrIO
M.W : 312.93
SMILES Code : OCC1=CC(Br)=CC=C1I
MDL No. :MFCD09745850
Boiling Point : No data available
InChI Key :LBMPOOHWJBYWPY-UHFFFAOYSA-N
Pubchem ID :15339730

Safety of [ 199786-58-8 ]

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

Calculated chemistry of [ 199786-58-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.14
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 52.99
TPSA ?

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

20.23 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.13
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

2.38
Log Po/w (WLOGP)?

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

2.39
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.

3.17
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

3.32
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.68

Water Solubility

Log S (ESOL):?

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

-3.66
Solubility 0.0688 mg/ml ; 0.00022 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.

-2.45
Solubility 1.12 mg/ml ; 0.00358 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

-4.01
Solubility 0.0304 mg/ml ; 0.0000973 mol/l
Class?

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

Moderately 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

Yes
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.

-6.52 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.

0.55

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

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<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)

1.9

Application In Synthesis [ 199786-58-8 ]

* 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 [ 199786-58-8 ]

[ 199786-58-8 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 199786-58-8 ]
  • [ 689291-89-2 ]
YieldReaction ConditionsOperation in experiment
98% With dipyridinium dichromate; In dichloromethane; at 20℃; for 4h;Inert atmosphere; To a stirred solution of PDC (11.0 g, 0.0288 mol) in CH2Cl2 (60 mL) was added a solution of 11 (4.50 g, 0.0144 mol) in CH2Cl2 (20 mL). The mixed content was stirred for 4 h at rt. The solvent was then removed under vacuum to give the crude product of 12, which was purified by silica flash column chromatography (hexanes/CH2Cl2, 7:3) to give compound 12 (4.40 g, 0.0142 mol, 98%) as a white solid.
93% With oxalyl dichloride; dimethyl sulfoxide; triethylamine; In dichloromethane; at -70 - -10℃; for 1.25h;Inert atmosphere; A solution of oxalyl chloride (1 .99 mL, 23.04 mmol, 1 .6 equiv) in DCM (25 mL) was cooled to -70C and DMSO (2.44 mL, 34.5 mmol, 2.4 equiv) in DCM (25 mL) was added at -65C to -70C. The reaction mixture stirred for 10 minutes under nitrogen atmosphere at - 70C and then (5-bromo-2-iodophenyl)methanol (4.55 g, 14.4 mmol, 1 .0 equiv) in DCM (100 mL) was added. The reaction mixture was stirred at -65C for 15 minutes and triethylamine (10 mL, 72 mmol, 5.0 equiv) was added. The reaction mixture was allowed to warm to -10C and stir for 1 h. Water (40 mL) was added and the reaction mixture was allowed to warm to room temperature. The organic layer was separated and evaporated to obtain 5-bromo-2-iodobenzaldehyde (4.2 g, 93 %) as white solid. 1H NMR (400 MHz.CDCb) δ ppm 7.45 (d, J=7.6 Hz, 1 H), 7.81 (d, J=1 1 .6 Hz, 1 H), 7.98 (d, J=1 .6 Hz, 1 H), 9.97 (s, 1 H).
A solution of oxalyl chloride (1.53 g, 0.012 mol) in CH2Cl2 (15 ML) was cooled to -70 C., and DMSO (1.41 g, 0.018 mol) in CH2Ck (15 ML) was added at -65 to -70 C. The mixture was stirred under nitrogen for 10 minutes at -70 C. and then treated with the product from Example 62B (2.35 g, 7.5 mmol) in 60 ML CH2Cl2.The slurry was stirred at -65 C. for 15 minutes and treated with triethylamine (3.8 g, 0.037 mol).The mixture was allowed to warm to -10 C. over 1 hour.The mixture was treated with 20 ML of water and allowed to warm to room temperature.The organic layer was separated and concentrated to provide the title compound. 1H NMR (CDCl3, 400 MHz) δ 9.97 (s, 1H), 7.97 (d, J=4 Hz, 1H), 7.79 (d, J=8 Hz, 1H), 7.40 (dd, J=4, 8 Hz, 1H). MS (DCl/NH3) [M+NH4]+ at 328.
With oxalyl dichloride; dimethyl sulfoxide; triethylamine; In dichloromethane; at -70 - -10℃; for 1.25h; A solution of oxalyl chloride (1.53 g, 0.012 mol) in CH2Cl2 (15 mL) was cooled to -70 C., and DMSO (1.41 g, 0.018 mol) in CH2Cl2 (15 mL) was added at -65 to -70 C. The mixture was stirred under nitrogen for 10 minutes at -70 C. and then treated with the product from Example 15B (2.35 g, 7.5 mmol) in 60 mL CH2Cl2. The slurry was stirred at -65 C. for 15 minutes and treated with triethylamine (3.8 g, 0.037 mol). The mixture was allowed to warm to -10 C. over 1 hour. The mixture was treated with 20 mL of water and allowed to warm to room temperature. The organic layer was separated and concentrated to provide the title compound. 1H NMR (CDCl3, 400 MHz) δ 9.97 (s, 1H), 7.97 (d, J=4 Hz, 1H), 7.79 (d, J=8 Hz, 1H), 7.40 (dd, J=4, 8 Hz, 1H). MS (DCl/NH3) [M+NH4]+ at 328.
Example 15C 5-Bromo-2-iodobenzaldehyde A solution of oxalyl chloride (1.53 g, 0.012 mol) in CH2Cl2 (15 mL) was cooled to -70 C., and DMSO (1.41 g, 0.018 mol) in CH2Cl2 (15 mL) was added at -65 to -70 C. The mixture was stirred under nitrogen for 10 minutes at -70 C. and then treated with the product from Example 15B (2.35 g, 7.5 mmol) in 60 mL CH2Cl2. The slurry was stirred at -65 C. for 15 minutes and treated with triethylamine (3.8 g, 0.037 mol). The mixture was allowed to warm to -10 C. over 1 hour. The mixture was treated with 20 mL of water and allowed to warm to room temperature. The organic layer was separated and concentrated to provide the title compound. 1H NMR (CDCl3, 400 MHz) δ 9.97. (s, 1H), 7.97 (d, J=4 Hz, 1H), 7.79 (d, J=8 Hz, 1H), 7.40 (dd, J=4, 8 Hz, 1H). MS (DCl/NH3) [M+NH4]+ at 328.
With dipyridinium dichromate; In dichloromethane; at 20℃; for 4h; The compound was synthesized according to the published procedure. [Zhou, N.; Wang, L.; Thompson, D. W.; Zhao, Y. Org. Lett. 2008, 10 (14), 3001-3004] Compound L15 and pyridinium dichromate (7.2 g, 19.2 mmol, 2 eq.) were dissolved in dry dichloromethane (40 ml) and the mixture was stirred at room temperature for 4 hours. The mixture was filtered through celite, washed with diethyl ether and solvents were evaporated. The solid was adsorbed on silica gel in a mixture of cyclohexane/acetone and it was purified by flash column chromatography on silica gel (cyclohexane to 20% ethyl acetate modified with 10% methanol (v/vi)), yielded 2.3 g (77%) of the title compound as a white solid (85% NMR purity). 1H NMR (401 MHz, Chloroform-d) δ 9.99 (s, 1H), 7.99 (d, J= 2.5 Hz, 1H), 7.81 (d, J= 8.4 Hz, 1H), 7.41 (dd, J= 8.4, 2.5 Hz, 1H). 13C NMR (101 MHz, Chloroform-d) δ 194.45, 141.95, 138.37, 136.47, 133.24, 123.63, 98.39. MS (CI-QMS) m/z: [M + H]+ calcd for C7H5BrIO, 310.9; found, 310.9.

 

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