Home Cart Sign in  
Chemical Structure| 884497-46-5 Chemical Structure| 884497-46-5

Structure of 884497-46-5

Chemical Structure| 884497-46-5

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

,{[proInfo.pro_purity]}

4.5 *For Research Use Only !

{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size Price VIP Price

US Stock

Global Stock

In Stock
{[ item.pr_size ]} Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

  • {[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

  • 1-2 Day Shipping
  • High Quality
  • Technical Support
Product Citations

Alternative Products

Product Details of [ 884497-46-5 ]

CAS No. :884497-46-5
Formula : C8H8FNO2
M.W : 169.15
SMILES Code : O=C(OC)C1=CC(F)=CC(N)=C1
MDL No. :MFCD05863683
Boiling Point : No data available
InChI Key :YKEJVXMOMKWEPV-UHFFFAOYSA-N
Pubchem ID :3807862

Safety of [ 884497-46-5 ]

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

Computational Chemistry of [ 884497-46-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.12
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 42.08
TPSA ?

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

52.32 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.65
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

1.6
Log Po/w (WLOGP)?

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

1.62
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

1.4
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.6

Water Solubility

Log S (ESOL):?

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

-2.13
Solubility 1.24 mg/ml ; 0.00733 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.

-2.31
Solubility 0.828 mg/ml ; 0.0049 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

-2.39
Solubility 0.692 mg/ml ; 0.00409 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.

-6.2 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<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)

1.45

Application In Synthesis of [ 884497-46-5 ]

* 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 [ 884497-46-5 ]

[ 884497-46-5 ] Synthesis Path-Upstream   1~7

  • 1
  • [ 1342063-52-8 ]
  • [ 884497-46-5 ]
YieldReaction ConditionsOperation in experiment
88% With 5%-palladium/activated carbon; hydrogen In methanol; water for 6 h; Inert atmosphere To a 3 liter round bottom flask was charged with 500 ml H2SO4. Fuming nitric acid was added (40 mL) and the mixture gently stirred. 2-Bromo-5-fluorobenzoic acid (60 g, 219 mmol) was added in 5 g portions over 90 minutes at 5-10°C. The mixture was stirred for 60 minutes at which time the reaction was completed. The mixture was poured into 1 liter of an ice/water mixture and extracted with EtOAc (3x600 mL). The combined organic extracts are dried (MgSO4) and concentrated under reduced pressure to give a yellow solid. The solid was suspended in hexanes and stirred for 30 minutes. The soild was collected on filter to provide 2-bromo-5-fluoro-3-nitrobenzoic acid as yellow solid (35 g, 49percent). To the solution of 2-bromo-5-fluoro-3-nitrobenzoic acid (35 g) in MeOH (400 mL) was added SOCl2 (40 mL) drop-wise at 10-15 °C. The reaction was then stirred at 65°C for 1 h. After cooling to room temperature, the solvent was evaporated in vacuum to afford a residue, which was chromatographed on silica gel using gradient eluant of 0-100percent EtOAc in hexane to provide methyl 2-bromo-5-fluoro-3-nitrobenzoate (20g, 84percent). To a solution of 2-bromo-5-fluoro-3-nitrobenzoate (20 g, 278 mmol) in EtOH/CH3COOH (200 mL/ 200 mL) was added iron powder (25 g, 55mmol). The mixture was vigorously stirred and heated to 85 °C for 1h. After cooling, the mixture was diluted with water and basified with NaHCO3 (PH=8), extracted with ethyl acetate (450mlx3). The combined organic layer was washed with brine (500ml), dried over MgSO4, filtered, and evaporated in vacuum. The residue was applied to flash column chromatography (silica gel) to give methyl 3-amino-2-bromo-5- fluorobenzoate (15.6 g,87percent) as red oil. To a solution of 3-amino-2-bromo-5-fluorobenzoate (2.48 g, 10 mmol) in MeOH (80 mL) was added Pd/C (0.5 g, 5percent, 50percent water), the mixture was stirred at atmosphere of hydrogen for about 6.0 h. Then the mixture was filtered, washed with MeOH (10 mL). The filtrate was concentrated and recrystallized with MeOH (2.5 mL) to afford methyl 3-amino-5-fluorobenzoate (1.48 g, 88percent) as a brown solid. 1H NMR (DMSO-d6) δ 7.04 (t, 1H, J=l .8 Hz), 6.74-6.76 (m, 1H), 6.55-6.80 (m, 1H),6.58 (m, 1H), 3.82 (s, 3H).
88% With 5%-palladium/activated carbon; hydrogen In methanol for 6 h; To a solution of 3-amino-2-bromo-5-fluorobenzoate (2.48 g, 10 mmol) in MeOH (80 mL) was added Pd/C (0.5 g, 5percent, 50percent water), the mixture was stirred at atmosphere of hydrogen for about 6.0 h.
Then the mixture was filtered, washed with MeOH (10 mL).
The filtrate was concentrated and recrystallized with MeOH (2.5 mL) to afford methyl 3-amino-5-fluorobenzoate (1.48 g, 88percent) as a brown solid. 1H NMR (DMSO-d6) δ 7.04 (t, 1H, J=1.8 Hz), 6.74-6.76 (m, 1H), 6.55-6.80 (m, 1H), 6.58 (m, 1H), 3.82 (s, 3H).
88% With 5%-palladium/activated carbon; hydrogen In water at 20℃; for 6 h; Methyl 3-amino-2-bromo-5-fluorobenzoate (2.48 g, 10 mmol) was dissolved in methanol (80 mL) and palladium on carbon (0.5 g, 5percent, 50percent water) added. The mixture was stirred for 6 hours at room temperature under a standard atmosphere of hydrogen. The reaction mixture was filtered through celite, washed with methanol (10ml) and the filtrate was concentrated. Recrystallization from methanol (2.5mL) gave methyl 3-amino-5-fluorobenzoate (1.48g, 88percent) as a brown solid.
References: [1] Patent: WO2013/97226, 2013, A1, . Location in patent: Page/Page column 46; 47.
[2] Patent: US2015/18356, 2015, A1, . Location in patent: Paragraph 0276.
[3] Patent: TWI588144, 2017, B, . Location in patent: Paragraph 0227; 0231.
  • 2
  • [ 67-56-1 ]
  • [ 884497-46-5 ]
YieldReaction ConditionsOperation in experiment
100% at 0℃; for 12 h; Reflux Example 1347-Fluoro-3 ,3 -dimethyl-2- (3 -morpholin-4-yl-phenyl) - 1 ,2,3 ,4-tetrahydro-quinoline-5- carboxylic acid To a stirred solution of 3-amino-5-fiuoro-benzoic acid (25 g, 161 mmol) in methanol (300 mL) was added thionyl chloride (30 mL, 403 mmol) dropewise at 0 °C . Then the mixture solution was refluxed for 12 hours before cooling to room temperature. Then the reaction mixture was concentrated in vacuo and the residue was dissolved in ethyl acetate (500 mL), washed with saturated aqueous sodium bicarbonate solution (3 x 100 mL), dried over anhydrous sodium sulfate and concentrated in vacuo to afford 3-amino-5-fiuoro- benzoic acid methyl ester (27.5 g, quant.) as a pale-white solid: LC/MS m/e calcd for C8H8FN02 (M+H)+: 170.16, observed: 169.9.
100% at 0℃; for 12 h; Reflux To a stirred solution of 3-amino-5-fluoro-benzoic acid (25 g, 161 mmol) in methanol (300 mL) was added thionyl chloride (30 mL, 403 mmol) dropewise at 0° C. Then the mixture solution was refluxed for 12 hours before cooling to room temperature. Then the reaction mixture was concentrated in vacuo and the residue was dissolved in ethyl acetate (500 mL), washed with saturated aqueous sodium bicarbonate solution (3.x.100 mL), dried over anhydrous sodium sulfate and concentrated in vacuo to afford 3-amino-5-fluoro-benzoic acid methyl ester (27.5 g, quant.) as a pale-white solid: LC/MS m/e calcd for C8H8FNO2 (M+H)+: 170.16, observed: 169.9.
References: [1] Patent: WO2011/128251, 2011, A1, . Location in patent: Page/Page column 226-227.
[2] Patent: US2011/257151, 2011, A1, . Location in patent: Page/Page column 83; 84.
[3] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 15, p. 4436 - 4440.
  • 3
  • [ 883987-72-2 ]
  • [ 884497-46-5 ]
References: [1] Patent: US2013/190249, 2013, A1, . Location in patent: Page/Page column.
[2] Patent: US2015/31627, 2015, A1, . Location in patent: Page/Page column.
[3] Patent: WO2013/107291, 2013, A1, . Location in patent: Page/Page column 68.
[4] Patent: WO2015/10626, 2015, A1, . Location in patent: Page/Page column 69.
[5] Patent: US9242996, 2016, B2, . Location in patent: Page/Page column 280; 282.
  • 4
  • [ 14027-75-9 ]
  • [ 884497-46-5 ]
References: [1] Patent: US2013/190249, 2013, A1, .
[2] Patent: WO2013/107291, 2013, A1, .
[3] Patent: WO2015/10626, 2015, A1, .
[4] Patent: US2015/31627, 2015, A1, .
[5] Patent: WO2015/10297, 2015, A1, .
[6] Patent: US9242996, 2016, B2, .
  • 5
  • [ 394-28-5 ]
  • [ 884497-46-5 ]
References: [1] Patent: WO2013/97226, 2013, A1, .
[2] Patent: US2015/18356, 2015, A1, .
[3] Patent: TWI588144, 2017, B, .
  • 6
  • [ 1055331-73-1 ]
  • [ 884497-46-5 ]
References: [1] Patent: WO2013/97226, 2013, A1, .
[2] Patent: US2015/18356, 2015, A1, .
[3] Patent: TWI588144, 2017, B, .
  • 7
  • [ 328547-12-2 ]
  • [ 884497-46-5 ]
References: [1] Patent: WO2013/97226, 2013, A1, .
[2] Patent: US2015/18356, 2015, A1, .
[3] Patent: TWI588144, 2017, B, .
 

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 884497-46-5 ]

Fluorinated Building Blocks

Chemical Structure| 2475-81-2

A173129 [2475-81-2]

Methyl 2-amino-4-fluorobenzoate

Similarity: 0.95

Chemical Structure| 369-26-6

A238386 [369-26-6]

Methyl 3-amino-4-fluorobenzoate

Similarity: 0.93

Chemical Structure| 153774-39-1

A197000 [153774-39-1]

Allyl 3-amino-4-fluorobenzoate

Similarity: 0.92

Chemical Structure| 319-24-4

A130738 [319-24-4]

Methyl 2-amino-5-fluorobenzoate

Similarity: 0.92

Chemical Structure| 185629-32-7

A142432 [185629-32-7]

Methyl 4-amino-3-fluorobenzoate

Similarity: 0.92

Aryls

Chemical Structure| 2475-81-2

A173129 [2475-81-2]

Methyl 2-amino-4-fluorobenzoate

Similarity: 0.95

Chemical Structure| 369-26-6

A238386 [369-26-6]

Methyl 3-amino-4-fluorobenzoate

Similarity: 0.93

Chemical Structure| 153774-39-1

A197000 [153774-39-1]

Allyl 3-amino-4-fluorobenzoate

Similarity: 0.92

Chemical Structure| 319-24-4

A130738 [319-24-4]

Methyl 2-amino-5-fluorobenzoate

Similarity: 0.92

Chemical Structure| 185629-32-7

A142432 [185629-32-7]

Methyl 4-amino-3-fluorobenzoate

Similarity: 0.92

Esters

Chemical Structure| 2475-81-2

A173129 [2475-81-2]

Methyl 2-amino-4-fluorobenzoate

Similarity: 0.95

Chemical Structure| 369-26-6

A238386 [369-26-6]

Methyl 3-amino-4-fluorobenzoate

Similarity: 0.93

Chemical Structure| 153774-39-1

A197000 [153774-39-1]

Allyl 3-amino-4-fluorobenzoate

Similarity: 0.92

Chemical Structure| 319-24-4

A130738 [319-24-4]

Methyl 2-amino-5-fluorobenzoate

Similarity: 0.92

Chemical Structure| 185629-32-7

A142432 [185629-32-7]

Methyl 4-amino-3-fluorobenzoate

Similarity: 0.92

Amines

Chemical Structure| 2475-81-2

A173129 [2475-81-2]

Methyl 2-amino-4-fluorobenzoate

Similarity: 0.95

Chemical Structure| 369-26-6

A238386 [369-26-6]

Methyl 3-amino-4-fluorobenzoate

Similarity: 0.93

Chemical Structure| 153774-39-1

A197000 [153774-39-1]

Allyl 3-amino-4-fluorobenzoate

Similarity: 0.92

Chemical Structure| 319-24-4

A130738 [319-24-4]

Methyl 2-amino-5-fluorobenzoate

Similarity: 0.92

Chemical Structure| 185629-32-7

A142432 [185629-32-7]

Methyl 4-amino-3-fluorobenzoate

Similarity: 0.92