Cat.NO.:A205155 Purity:97%
Product Details of [ 1006-41-3 ]
CAS No. : | 1006-41-3 |
Formula : |
C7H4BrFO2 |
M.W : |
219.01
|
SMILES Code : | O=C(O)C1=CC=C(F)C=C1Br |
MDL No. : | MFCD00055370 |
InChI Key : | RRKPMLZRLKTDQV-UHFFFAOYSA-N |
Pubchem ID : | 1268169 |
Safety of [ 1006-41-3 ]
GHS Pictogram: | ![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Computational Chemistry of [ 1006-41-3 ] 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 |
37.3 Ų |
Lipophilicity
Log Po/w (iLOGP)?
iLOGP: in-house physics-based method implemented from |
1.47 |
Log Po/w (XLOGP3)?
XLOGP3: Atomistic and knowledge-based method calculated by |
2.27 |
Log Po/w (WLOGP)?
WLOGP: Atomistic method implemented from |
2.71 |
Log Po/w (MLOGP)?
MLOGP: Topological method implemented from |
2.79 |
Log Po/w (SILICOS-IT)?
SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.32 |
Consensus Log Po/w?
Consensus Log Po/w: Average of all five predictions |
2.31 |
Water Solubility
Log S (ESOL):?
ESOL: Topological method implemented from |
-2.97 |
Solubility | 0.237 mg/ml ; 0.00108 mol/l |
Class?
Solubility class: Log S scale |
Soluble |
Log S (Ali)?
Ali: Topological method implemented from |
-2.69 |
Solubility | 0.447 mg/ml ; 0.00204 mol/l |
Class?
Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)?
SILICOS-IT: Fragmental method calculated by |
-2.91 |
Solubility | 0.269 mg/ml ; 0.00123 mol/l |
Class?
Solubility class: Log S scale |
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) |
No |
CYP1A2 inhibitor?
Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor?
Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor?
Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor?
Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor?
Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)?
Skin permeation: QSPR model implemented from |
-6.02 cm/s |
Druglikeness
Lipinski?
Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose?
Ghose filter: implemented from |
None |
Veber?
Veber (GSK) filter: implemented from |
0.0 |
Egan?
Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge?
Muegge (Bayer) filter: implemented from |
0.0 |
Bioavailability Score?
Abbott Bioavailability Score: Probability of F > 10% in rat |
0.56 |
Medicinal Chemistry
PAINS?
Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk?
Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness?
Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility?
Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.33 |
Application In Synthesis of [ 1006-41-3 ]
* 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 [ 1006-41-3 ]
[ 1006-41-3 ] Synthesis Path-Downstream 1~2
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; potassium nitrate; at 0 – 20℃; for 3.16667h; | Potassium nitrate (11.54 g, 114 mmol) was added portionwise to a solution of 2-bromo-4-fluorobenzoic acid (25 g, 114 mmol) in sulfuric Acid (228 mL) <n=”138″/>at 0 0C over 10 min. The reaction mixture was stirred for 3 h at ambient temperature. The reaction mixture was poured onto ice. The resulting precipitate was washed with water and dried in vacuo to yield a mixture of 21A and 2-Br-4-F-6-nitrobenzoic acid (9: 1) as a white solid (19.5 g). 7 g of this solid was purified by prep HPLC (0.1% TFA, H2OMeOH, 35% to 60%) to yield 21A (5.6 g, 21.21 mmol) as a white solid. MS (ESI) m/z 262.1/264.1 (M-H)”. 1H NMR (400 MHz, CD3OD) delta ppm 7.91 (d, J=10.44 Hz, 1 H) 8.61 (d, J=8.25 Hz, 1 H).; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With sulfuric acid; nitric acid; In water; at 20℃; for 1h;Cooling with ice; | Fuming nitric acid (4 ml, 45.60 mmol) was added dropwise to a mixed solution of 2-bromo-4-fluorobenzoic acid (10 g, 45.66 mmol) and concentrated sulfuric acid (34 ml) under ice-cooling.The reaction system was dripped into ice water and stirred rapidly for 1 hour. The solid was collected by filtration, washed with ice water and dried to give 10.40 g of a white solid (10.4 g), which was washed with water and evaporated to dryness to give a white solid Solid, yield 86%. |
73% | With sulfuric acid; nitric acid; at 0 – 20℃; for 3h; | Fuming 113 nitric acid (8 mL) was added dropwise to a mixture of 114 2-bromo-4-fluorobenzoic acid (20 g, 91.2 mmol) in 115 concentrated sulfuric acid (68 mL) at 0 C. After stirring at room temperature for 3 h, the mixture was poured into ice water and stirred rapidly for 1 hour. The solid was collected by filtration, washed with water and dried to give 116 compound 16A (17.59 g, 73% yield) as a white solid: 1H NMR (400 MHz, CDCl3) delta 8.81 (d, J=8 Hz, 1H), 7.73 (d, J=10 Hz, 1H). |
52% | With sulfuric acid; potassium nitrate; at 0 – 20℃; for 3h; | To a solution of 183 (25 g, 114 mmol) in sulfuric acid (228 mL) is added potassium nitrate (11.5 g, 114 mmol) at 0 C over 10 minutes. After stirring at room temperature for 3 hours, the mixture is poured onto ice and the solid is collected by filtration, washed with water, dned,and purified by prep-HPLC (water/MeOH with 0.1% TFA, 35% to 60%) to give 184 as a white solid (5.6 g, 52% yield). (MS: [M+Hf 265.2) |
With sulfuric acid; potassium nitrate; at 0 – 20℃; for 3.16667h; | Intermediate 7: 6-amino-5-fluoroisoindolin-l-one; <n=”94″/>Intermediate 7A:; [00206] Potassium nitrate (11.54 g, 114 mmol) was added portionwise to a solution of 2-bromo-4-fluorobenzoic acid (25 g, 114 mmol) in sulfuric acid (228 mL) at 0 0C over 10 min. The reaction mixture was stirred for 3 h at ambient temperature. The reaction mixture was poured onto ice. The resulting precipitate was washed with water and dried in vacuo to yield a mixture of Intermediate 7 A and 2-Br-4-F-6- nitrobenzoic acid (9: 1) as a white solid (19.5 g). 7 g of this solid was purified by prep HPLC (0.1% TFA, H2OMeOH, 35% to 60%) to yield Intermediate 7A (5.6 g, 21.21 mmol) as a white solid. MS (ESI) m/z 262.1/264.1 (M-H)”. | |
With sulfuric acid; potassium nitrate; at 0 – 20℃; for 3h; | To a cooled solution of 2-bromo-4-fluorobenzoic acid (5.00 g, 22.83 mmol) in sulfuric acid (42.5 mL) at 0 C. was added potassium nitrate portionwise (2.31 g, 22.83 mmol) over 5 minutes with the resulting solution stirred at ambient temperature for 3 h. After this time the reaction mixture was poured onto ice and the resultant precipitate was filtered, washing with water and dried in vacuo for 60 h to afford a mixture of regioisomers favouring the title compound (4:1; 5.03 g, 70% yield) as an off-white solid. 1H NMR (250 MHz, DMSO-d6) delta [ppm] 8.51 (d, J=8.0 Hz, 1H), 8.17 (d, J=10.9 Hz, 1H). LCMS (Analytical Method A): Rt=0.91 min; MS (ESIPos) m/z=261.8/263.8 (M-H)-, Br isotope pattern. |
[2]Patent: US2018/291002,2018,A1 .Location in patent: Paragraph 0444; 0445.
[3]Patent: WO2017/176812,2017,A1 .Location in patent: Paragraph 0451.
[4]Patent: WO2008/79836,2008,A2 .Location in patent: Page/Page column 86-87.
[5]Patent: US2019/177279,2019,A1 .Location in patent: Paragraph 0861-0864.
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