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Structure of 4-Bromo-2-fluorobenzyl bromide
CAS No.: 76283-09-5
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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.
4.5
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Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
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CAS No. : | 76283-09-5 |
Formula : | C7H5Br2F |
M.W : | 267.92 |
SMILES Code : | FC1=CC(Br)=CC=C1CBr |
MDL No. : | MFCD00055467 |
InChI Key : | XMHNLZXYPAULDF-UHFFFAOYSA-N |
Pubchem ID : | 2733660 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H301-H314-H412 |
Precautionary Statements: | P280-P301+P310-P305+P351+P338-P310 |
Class: | 8(6.1) |
UN#: | 2923 |
Packing Group: | Ⅱ |
Num. heavy atoms | 10 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 1.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 46.94 |
TPSA ? Topological Polar Surface Area: Calculated from |
0.0 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.49 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
3.27 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
3.75 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.25 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.93 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.54 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.94 |
Solubility | 0.0308 mg/ml ; 0.000115 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.94 |
Solubility | 0.304 mg/ml ; 0.00114 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.79 |
Solubility | 0.00439 mg/ml ; 0.0000164 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
Low |
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) |
Yes |
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) |
Yes |
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 |
-5.61 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
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 |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.7 |
* 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 potassium carbonate; In N,N-dimethyl-formamide; chlorobenzene; | The starting material was obtained as follows: Anhydrous potassium carbonate (10.7 g.) and 7-trifluoromethyl indoline-2,3-dione (14.4 g.) were stirred in N,N-dimethylformamide (DMF) (100 ml.) for 30 minutes. A portion (78.9 ml.) of a 25percent w/v solution of 4-bromo-2-fluorobenzyl bromide in chlorobenzene was then added and the mixture was stirred at 75°-78° C. for 2 hours. The mixture was then cooled to ambient temperature and poured into water (400 ml.). Petrol 60-80 (200 ml.) was added to the aqueous mixture and the whole was stirred for 30 minutes. The solid which formed was separated by filtration to give 1-(4-bromo-2-fluorobenzyl)-7-trifluoromethyl indoline-2,3-dione (17.8 g.), m.p. 141°-143° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In acetonitrile; at 20℃; | Tert-butyl 2-oxospiro[indoline-3,3?-pyrrolidine]-1?-carboxylate (1 g, 3.4 mmol) was added to a round bottom flask containing a stir bar and dissolved in acetonitrile (15 mL). Potassium carbonate (940 mg, 6.8 mmol) was added, followed by 4-bromo-1-(bromomethyl)-2-fluorobenzene (929 mg, 3.4 mmol). The mixture was stirred at room temperature overnight, and then evaporated under reduced pressure. The resulting residue was partitioned between water and ethyl acetate. The organic layer was collected, and the water layer was extracted with an additional ethyl acetate (2×50 mL). The organic layers were combined, dried over magnesium sulfate, and evaporated to afford a colorless solid, which was used directly in the next step. To a microwave vial containing a stir bar was added tert-butyl 1-(4-bromo-2-fluorobenzyl)-2-oxospiro[indoline-3,3?-pyrrolidine]-1?-carboxylate (457 mg, 0.96 mmol), followed by 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (200 mg, 0.96 mmol), cesium carbonate (626 mg, 1.9 mmol), 1,1?-bis(diphenylphosphino)ferrocene]-dichloropalladium (II) dichloromethane adduct (78 mg, 0.096 mmol), and the mixture was suspended in THF/water (4 mL, 1:1). The vial was sealed, and the mixture was heated to 160 C. for 10 min. The organic layer was removed, filtered through celite and evaporated to afford an oil, which was re-dissolved in excess TFA. This solution was allowed to stir at room temperature for 2 h, and then TFA was evaporated under reduced pressure. The resulting oil was used directly in the next step. 1-(2-fluoro-4-(1-methyl-1H-pyrazol-4-yl)benzyl)spiro[indoline-3,3?-pyrrolidin]-2-one (75 mg, 0.2 mmol) was added to a vial containing a stir bar and dissolved in DMF (1 mL). Potassium carbonate (41 mg, 0.3 mmol) was added, followed by iodomethane (15 muL, 0.2 mmol). The vial was sealed, and the mixture was stirred at room temperature for 2 h. The suspension was filtered to remove solids, and then purified using an SCX cartridge to afford the title compound as a clear oil. LCMS: RT=0.59 min, >99% (at) 254 nm, >99% (at) 215 nm; m/z (M+1)+=391. 1H NMR (400 MHz, CDCl3, delta (ppm)): 7.7 (s, 1H), 7.6 (s, 1H), 7.5 (dd, J=7.4, 0.6 Hz, 1H), 7.3-7.1 (m, 4H), 7.1-7.0 (m, 1H), 6.8 (d, J=7.8 Hz, 1H), 5.0 (s, 2H), 4.0 (s, 3H), 3.1-3.0 (m, 1H), 3.0-2.9 (m, 2H), 2.8-2.7 (m, 1H), 2.5 (s, 3H), 2.5-2.4 (m, 1H), 2.1 (dt, J=12.8, 7.7 Hz, 1H), HRMS calculated for C23H24N4OF (M+H)+ m/z: 391.1934, measured: 391.1933. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: Compound 1 (10 mmol), anhydrous potassium carbonate (20 mmol, K2CO3) and DMF (20 mL) were added to a 100 mL-dry eggplant flask and stirred at room temperature for 30 min prior to addition of p-bromobenzyl bromide (12 mmol). The resulting mixture was maintained at 80 C for 3-8 h, and the reaction course was monitored using TLC. Upon the reaction completion, the mixture was cooled to room temperature before the addition of 100mL of water, and the system was extracted with ethyl acetate (30 mL 3). The organic phase was dried over anhydrous Na2SO4 and concentrated using rotary evaporator. The crude product 2 was used in the next step without further purification. |
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