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Chemical Structure| 132715-69-6 Chemical Structure| 132715-69-6

Structure of 132715-69-6

Chemical Structure| 132715-69-6

2-Bromo-3-fluorobenzoic acid

CAS No.: 132715-69-6

4.5 *For Research Use Only !

Cat. No.: A313948 Purity: 98%

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Product Details of [ 132715-69-6 ]

CAS No. :132715-69-6
Formula : C7H4BrFO2
M.W : 219.01
SMILES Code : BrC1=C(C(=O)O)C=CC=C1F
MDL No. :MFCD01569398
Boiling Point : No data available
InChI Key :KQRCBMPPEPNNDS-UHFFFAOYSA-N
Pubchem ID :302622

Safety of [ 132715-69-6 ]

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

Computational Chemistry of [ 132715-69-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 41.06
TPSA ?

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

37.3 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.39
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

2.24
Log Po/w (WLOGP)?

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

2.71
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.

2.79
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

2.32
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.29

Water Solubility

Log S (ESOL):?

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

-2.95
Solubility 0.248 mg/ml ; 0.00113 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.

-2.66
Solubility 0.48 mg/ml ; 0.00219 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

-2.91
Solubility 0.269 mg/ml ; 0.00123 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

No
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.

-6.05 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)

1.37

Application In Synthesis of [ 132715-69-6 ]

* 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 [ 132715-69-6 ]

[ 132715-69-6 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 132715-69-6 ]
  • [ 881415-28-7 ]
  • [ 881415-27-6 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid; nitric acid; at 0 - 20℃; for 2.16667h; Example 9: methyl 3-((2R)-l-(2-(3,4-dimethoxyphenyl)-2-(7-fluoro-3- oxoisoindolin-5-ylamino)acetyl)pyrrolidin-2-yl)-4-(isopropylsulfonyl)phenylcarbamate[00234] In a 50 mL round-bottomed flask 2-bromo-3-fluoro-benzoic acid (5 g,22.8 mmol) and sulfuric acid (15 mL) were stirred at 0 0C before adding fuming nitric acid (2 mL, 22.83 mmol, 90%) drop wise over 10 min. The reaction was stirred for 2 h at rt. The reaction was poured onto ice and the solids were isolated by filtration. The crude solids were purified on SiO2 (eluting with 0-100% EtOAc) to yield a 1: 1 mixture of region-isomers 9A and 2-bromo-3-fluoro-6-nitrobenzoic acid (3.7g, 63% yield). 1H NMR (400 MHz, CD3OD) delta ppm 7.48 (dd, J=9.23, 7.47 Hz, 1 H) 8.16 (dd, J=7.91, 2.64 Hz, 1 H) 8.26 (dd, J=9.23, 4.39 Hz, 1 H) 8.35 - 8.40 (m, 1 H).
With sulfuric acid; nitric acid; In water; at 0 - 20℃; for 1.5h; In a 1 L, three necked, round-bottomed flask fitted with a dropping funnel and a thermometer were charged 33 g (0.15 mol) of 2-bromo-3-fluoro-benzoic acid and 200 mL of concentrated sulfuric acid. After cooling to 0 C., 16 mL of HNO3 (70%) was added dropwise over 30 min keeping temperature at 10 or less degrees. After 1 h, the reaction mixture was poured into the crushed ice keeping temperature at 20 or less degrees. The mixture was extracted twice with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate. The solvent was removed under reduced pressure to give a mixture of 2-bromo-3-fluoro-6-nitro-benzoic acid and 2-bromo-3-fluoro-5-nitro benzoic acid (2:1) as brown solids in quantitative yield. 1H-NMR (400 MHz, CDCl3, delta, ppm) 2-bromo-3-fluoro-6-nitro-benzoic acid: 7.37 (dd, 1H), 8.27 (dd, 1H), 2-bromo-3-fluoro-5-nitro benzoic acid:
With sulfuric acid; nitric acid; at 0℃; for 1.5h; A solution of 2-bromo-3-fluorobenzoic acid (CAS registry 132715-69-6) (5 g, 22.83 mmol) inH2S04 conc. (15.82 ml, 297 mmol ) was cooled to 0C and was treated dropwise with fumingHNO3 (1.36 ml, 27.4 mmol). A white precipitate was formed. The resulting suspension wasstirred at 0C for 1.5 h. The mixture was poured onto ice water and stirred for 30 mm. Theresulting mixture was diluted with water and extracted with DCM. Then, the organic phases were dried over Na2SO4 and concentrated under reduced pressure. This afforded an off- white solid (5.67 g, 94%) of a mixture of 2-bromo-3-fluoro-6-nitrobenzoic acid (regioisomer 1) and 2-bromo-3-fluoro-5-nitrobenzoic acid (regioisomer 2) in a ratio of ca. 2:1, which wasused without separation for the next step.HPLC 1st regioisomer (69%) Rt= 0.33 mm; HPLC 2? regioisomer (30%) Rt= 0.52 mm.
With sulfuric acid; nitric acid; In water; at 20℃; for 2h; In an ice bath, fuming nitric acid (2mL, 22.83mmoL) was added dropwise 2-bromo-3-fluoro - benzoic acid (5g, 22.8mmol) and concentrated sulfuric acid (15mL) in the mixed solution.After the addition was complete, brought to room temperature stirred for 2 hours.Poured into ice water, a large number of solid was filtered, the solid washed with water and dried under high vacuum, a white solid 5.3g, mixture of intermediate 4c and 4e, (4c / 4e = 2/1), in a yield of 88%.Most of this mixture was used directly in the next reaction, a small amount was purified by column chromatography and identified as follows:

  • 2
  • [ 132715-69-6 ]
  • [ 881415-27-6 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid; nitric acid; In neat (no solvent); at 0 - 20℃; for 16h; To a solution of 2-bromo-3-fluorobenzoic acid (2 g, 9.17 mmol) in H2S04 (8 mL) was added HN03 (0.8 mL, 9.17 mmol) at 0 C. The reaction mixture was stirred for 16 hours at room temperature and was poured onto ice. The solid was isolated by filtration and purified by column chromatography to afford 2-bromo-3-fluoro-6-nitrobenzoic acid (500 mg, 20%, LC-MS 92%) as a pale yellow solid. NMR (400 MHz, DMSO-< delta (ppm): 8.35 (dd, / = 5.2 Hz, 9.6 Hz, 1H), 7.74-7.66 (m, 1H); MS (ESI) m/z: 263.9 [C7H3BrFN04-H]+.
 

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