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Chemical Structure| 2434-03-9

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Product Details of [ 2434-03-9 ]

CAS No. :2434-03-9
Formula : C5H2Br2O3
M.W : 269.88
SMILES Code : O=C(O)C1=CC(Br)=C(Br)O1
MDL No. :MFCD00092311
InChI Key :BHUVICYZDBUMIU-UHFFFAOYSA-N
Pubchem ID :4194832

Safety of [ 2434-03-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H317
Precautionary Statements:P280

Computational Chemistry of [ 2434-03-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 5
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 41.07
TPSA ?

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

50.44 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.55
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

2.56
Log Po/w (WLOGP)?

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

2.5
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.

1.24
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

2.08
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.99

Water Solubility

Log S (ESOL):?

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

-3.43
Solubility 0.1 mg/ml ; 0.000372 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.

-3.27
Solubility 0.146 mg/ml ; 0.000541 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

-2.69
Solubility 0.551 mg/ml ; 0.00204 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.

-6.13 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<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)

2.44

Application In Synthesis of [ 2434-03-9 ]

* 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 [ 2434-03-9 ]

[ 2434-03-9 ] Synthesis Path-Upstream   1~2

  • 1
  • [ 2434-03-9 ]
  • [ 3439-02-9 ]
YieldReaction ConditionsOperation in experiment
99% With ammonia; zinc In water at 0 - 7℃; 10.0 g (37.1 mmol) of 4,5-dibromofuran-2-carboxylic acid are provided in an aqueous ammonia solution (7.3percent) and cooled to 0° C. With vigorous stirring, 2.54 g (38.9 mmol) of zinc powder are added in portions such that the temperature does not exceed 7° C. The mixture is stirred at 0° C. for 10 minutes and an acidic pH is then established by the addition of an aqueous HCl solution. The suspension is extracted with ethyl acetate and the organic phase is dried over sodium sulfate, filtered and concentrated. 7.27 g (99percent of theory) of the title compound are obtained.1H-NMR (400 MHz, DMSO-d6): δ=13.5 (s, 1H), 8.17 (s, 1H), 7.40 (s, 1H).LC-MS (Method 1): Rt=1.52 min; MS (ESIpos): m/z=191 [M+H]+.
83.1%
Stage #1: With ammonium hydroxide; zinc In water at 20℃; for 6 h;
Stage #2: With hydrogenchloride In water
Step 1 4-Bromo-furan-2-carboxylic acid A mixture of 4,5-dibromo-furan-2-carboxylic acid; 28a (5.5 g, 20.3 mmol) and 18 mL of ammonium hydroxide was added to 63 mL of water followed by addition of zinc powder (1.46 g, 22.33 mmol). Upon completion of the addition, the reaction mixture was stirred at room temperature for 6 hours. The reaction was monitored by TLC until the disappearance of the starting materials. The mixture was adjusted to pH 3 with hydrochloric acid (1 N) to form a copious amount of precipitates. The mixture was filtered and the filter cake was washed with n-hexane (15 mL.x.4) and dried to obtain the title compound 4-bromo-furan-2-carboxylic acid 28b (3.2 g, yield 83.1 percent) as a white solid. MS m/z (ESI): 188.7 [M-1]
83.1%
Stage #1: at 20℃; for 6 h;
Stage #2: With hydrogenchloride In water
Example 22: (Z)-4-(2-Hydroxy-3-{N'-[3-methyl-5-oxo-1-(5,6,7,8-tetrahydro-naphthal-2-yl)-1,5-di-hydro- pyrazol-4-ylidene]-hydrazino}-phenyl)-furan-2-carboxylic acid bis-(ethanolamine); Step 1; 4-Bromo-furan-2-carboxylic acid; A mixture of 4,5-dibromo-furan-2-carboxylic acid 22a (5.5 g, 20.3 mmol) and 18 mL of ammonium hydroxide was added to 63 mL of water followed by addition of zinc powder (1.46 g, 22.33 mmol). Upon completion of the addition, the reaction mixture was stirred at room temperature for 6 hours. The mixture was adjusted to pH 3 with 1 M hydrochloric acid to form a great quantity of precipitates. The mixture was filtered and the filter cake was washed with n-hexane (15 mLx4) and dried to obtain the title compound 4-bromo-furan-2-carboxylic acid 22b (3.2 g, yield 83.1 percent) as a white solid. MS m/z (ESI): 188.7 [M-1]
83.1% With ammonium hydroxide; zinc In water at 20℃; for 6 h; At room temperature, 4,5-dibromofuran-2-carboxylic acid 22a (5.5g, 20.30 mmol), 18mL of aqueous ammonia in 63mL water, and zinc powder (1.46g, 22.33 mmol) were mixed. After addition was complete, it was stirred at room temperature for 6 hours. The reaction solution was adjusted pH = 3 with 1M hydrochloric acid. The solid precipitate was filtered. The filter cake was washed with n-hexane (15mL × 4) and dried to give the title product 4-bromofuran-2-carboxylic acid 22b (3.2g, white solid), yield: 83.1percent.
46%
Stage #1: at 0 - 7℃; for 1 h;
Stage #2: at 20℃;
Step C: 4-Bromo-2-furoic acid. 4,5-Dibromo-2-furoic acid (24.51 g, 90.8 mmol) was dissolved in a mixture of water (280 mL) and aq. NH4OH (33percent NH3; 80 mL) and <n="20"/>cooled in an ice bath. The mixture was stirred rapidly as zinc dust (6.23 g, 95.3 mmol) was added in portions while keeping the internal temperature below 7 0C. The mixture was stirred at 0 0C for 30 min. An additional portion of zinc dust (0.5 g, 7.6 mmol) was added and the mixture was allowed to stir at 0 0C for 30 min. The reaction was acidified to pH 1 with cone. HCI causing precipitation of the product. The mixture was cooled to 10 0C, and the product was collected by suction filtration, washed with water, and air dried to provide 8.0 g (46percent) of the desired acid. Additional product could be obtained by extraction of the filtrate with DCM and recrystallization of the crude extract from water. 1H NMR (CDCI3): 7.76 (d, J = 0.8, 1 H), 7.14 (d, J = 0.8, 1 H).
46% With ammonia; zinc In water at 0 - 7℃; for 1 h; C. 4-Bromo-2-furoic acid. ; 4,5-Dibromo-2-furoic acid (24.51 g, 90.8 mmol) was dissolved in a mixture of water (280 mL) and aq. NH4OH (33percent NH3; 80 mL) and cooled in an ice bath. The mixture was stirred rapidly as zinc dust (6.23 g, 95.3 mmol) was added in portions while keeping the internal temperature below 7° C. The mixture was stirred at 0° C. for 30 min. HPLC analysis of an aliquot of the reaction mixture indicated some starting material remaining. An additional portion of zinc dust (0.5 g, 7.6 mmol) was added and the mixture was stirred at 0° C. for 30 min. HPLC analysis of an aliquot indicated only a trace of starting material as well as formation of a small amount of 2-furoic acid from over-reduction. The mixture was acidified to pH 1 with conc. HCl causing precipitation of the product. The mixture was cooled to 10° C., and the product was collected by suction filtration, washed with water, and air dried to provide 8.0 g (46percent) of the desired acid. Additional product could be obtained by extraction of the filtrate with DCM and recrystallization of the crude extract from water. 1H NMR (400 MHz, CDCl3): 7.76 (d, J=0.8, 1H), 7.14 (d, J=0.8, 1H).
665 mg With ammonium hydroxide; zinc In water at 20℃; for 3 h; 4,5-Dibromofuran-2-carboxylic acid (9, 1.00 g, 3.7 mmol) was suspended in water (11 mL) and NH4OH (3.5 mL) with vigorous stirring at ambient temperature. Powdered zinc metal (1.30 g, 20.3 mmol) was added, and the mixture was allowed to stir at ambient temperature for 3 h. The reaction mixture was filtered through a pad of Celite and acidified (pH 2) with 2 N HCl. The filtrate was extracted with EtOAc (4 * 50 mL), dried (Na2SO4), and concentrated to dryness under reduced pressure to provide 665 mg of a white powder. To this crude intermediate dissolved in MeOH (12 mL) was added concentrated sulfuric acid (80 μL) while stirring. The resulting solution was heated to reflux and stirred overnight. The reaction mixture was allowed to cool to room temperature followed by concentration under vacuum. The resulting crude residue was then partitioned between saturated aqueous NaHCO3 and diethyl ether, and the aqueous layer was further extracted with diethyl ether (2 * 40 mL). The combined ether solutions were washed with brine (20 mL), dried (Na2SO4) and concentrated to dryness under reduced pressure to provide 652 mg (3.18 mmol, 86percent) of the desired product as a clear oil.

References: [1] Patent: US2012/22059, 2012, A1, . Location in patent: Page/Page column 10-11.
[2] Journal of Medicinal Chemistry, 2008, vol. 51, # 3, p. 407 - 416.
[3] Patent: EP2236500, 2010, A1, . Location in patent: Page/Page column 49.
[4] Patent: EP2441457, 2012, A1, . Location in patent: Page/Page column 31.
[5] Patent: TWI530497, 2016, B, . Location in patent: Page/Page column 61.
[6] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 18, p. 5470 - 5474.
[7] Patent: WO2008/124518, 2008, A1, . Location in patent: Page/Page column 18-19.
[8] Patent: US2006/69286, 2006, A1, . Location in patent: Page/Page column 25.
[9] Patent: US2009/286798, 2009, A1, . Location in patent: Page/Page column 29-30.
[10] Patent: WO2004/58717, 2004, A1, . Location in patent: Page 83-84.
[11] Patent: US2011/118269, 2011, A1, . Location in patent: Page/Page column 16.
[12] Patent: WO2011/159781, 2011, A2, . Location in patent: Page/Page column 63-64.
[13] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 19, p. 5763 - 5773.
[14] Patent: WO2007/131991, 2007, A1, . Location in patent: Page/Page column 107.
[15] Patent: WO2007/138072, 2007, A2, . Location in patent: Page/Page column 91.
  • 2
  • [ 2434-03-9 ]
  • [ 88-14-2 ]
  • [ 3439-02-9 ]
References: [1] Patent: US2005/54627, 2005, A1, . Location in patent: Page/Page column 43.
[2] Patent: US2005/54626, 2005, A1, . Location in patent: Page/Page column 42.
 

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