Structure of 132715-69-6
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
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 |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.39 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.24 |
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 |
2.29 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.95 |
Solubility | 0.248 mg/ml ; 0.00113 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.66 |
Solubility | 0.48 mg/ml ; 0.00219 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 |
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 |
-6.05 cm/s |
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 |
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) |
1.37 |
* 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.
Yield | Reaction Conditions | Operation 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: |
Yield | Reaction Conditions | Operation 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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