Structure of 5-Bromo-2-furaldehyde
CAS No.: 1899-24-7
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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. : | 1899-24-7 |
Formula : | C5H3BrO2 |
M.W : | 174.98 |
SMILES Code : | O=CC1=CC=C(Br)O1 |
MDL No. : | MFCD00159501 |
InChI Key : | WJTFHWXMITZNHS-UHFFFAOYSA-N |
Pubchem ID : | 600328 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302+H312+H332-H315-H319-H335 |
Precautionary Statements: | P261-P280-P305+P351+P338 |
Num. heavy atoms | 8 |
Num. arom. heavy atoms | 5 |
Fraction Csp3 | 0.0 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 31.8 |
TPSA ? Topological Polar Surface Area: Calculated from |
30.21 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.26 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.81 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.85 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.27 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.13 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
1.46 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.46 |
Solubility | 0.604 mg/ml ; 0.00345 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.06 |
Solubility | 1.51 mg/ml ; 0.00863 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.41 |
Solubility | 0.684 mg/ml ; 0.00391 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) |
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) |
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 |
-6.08 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 |
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<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.01 |
* 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 |
---|---|---|
95% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; at 70.0℃;Inert atmosphere; Sealed tube; | General procedure: A bromo-aldehyde (1 mmol), boronic acid (1.1e1.3 mmol), tetrakis(triphenylphosphine)palladium (0.05 mmol), potassium carbonate(3 mmol), water (3 ml), ethanol (4 ml) and toluene (4 ml)were added to a round-bottomed flask. The reaction mixture wasflushed with argon, sealed under septa and heated at 70 C overnight.After cooling to room temperature, water (50 ml) was added,and product was extracted with ethyl acetate (3 x 50 ml). Combinedextracts were washed with brine, dried with anhydrousmagnesium sulfate and evaporated under reduced pressure. Theproduct was purified by column chromatography on silica withchloroform or a mixture of methanol and chloroform (1:9). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; at 80℃; for 72h;Reflux; | General procedure for the Suzuki coupling. Method A To a solution of the halogen-substituted heteroaryl aldehyde (2.7 mmol) of formula (IV) and the corresponding boronic acid (3.2 mmol) of formula R2-B(OH)2 (R2 being as defined above) in THF (20.0 mL) a solution of sodium bicarbonate (8.0 mmol) in water (9.0 mL) was added. The reaction mixture was stirred at room temperature for 5 minutes, and a solution of Pd(PPh3)4 (0.2 mmol) in THF (5.0 mL) was added. The reaction mixture was refluxed at 80 C for three days, cooled to room temperature and diluted with ethyl acetate (150.0 mL) and water (50.0 mL). The aqueous layer was extracted with ethyl acetate (2 × 25.0 mL), and the combined organic layers were washed with brine, dried with anhydrous sulfate, filtered and concentrated under vacuum to afford the corresponding aldehyde of formula (II). Example 1. Synthesis of 5-(2,4-dimethoxy-phenyl)-furan-2-carbaldehyde [Show Image] Synthesized using method A. The compound did not need any further purification. 630.0 mg; 100% yield. MS (ES): M/z= 233 (M+H)+ 1H NMR (400 MHz, CDCl3, δ ppm): 9.59 (s, 1 H), 7.98 (d, J = 8.7 Hz, 1 H), 7.31 (d, J = 3.7 Hz, 1 H), 7.00 (d, J = 3.7 Hz, 1 H), 6.60 (dd, J = 8.7, 2.3 Hz, 1 H), 6.53 (d, J = 2.3 Hz, 1 H), 3.94 (s, 3H), 3.87 (s, 3H). |
100% | General procedure for the Suzuki coupling. Method A To a solution of the halogen-substituted heteroaryl aldehyde (2.7 mmol) of formula (IV) and the corresponding boronic acid (3.2 mmol) of formula R2-B(OH)2 (R2 being as defined above) in THF (20.0 ml.) a solution of sodium bicarbonate (8.0 mmol) in water (9.0 ml.) was added. The reaction mixture was stirred at room temperature for 5 minutes, and a solution of Pd(PPh3)4 (0.2 mmol) in THF (5.0 ml.) was added. The reaction mixture was refluxed at 80 C for three days, cooled to room temperature and diluted with ethyl acetate (150.0 ml.) and water (50.0 ml_). The aqueous layer was extracted with ethyl acetate (2 x 25.0 ml_), and the combined organic layers were washed with brine, dried with anhydrous sulfate, filtered and concentrated under vacuum to afford the corresponding aldehyde of formula (II).xample 1. Synthesis of 5-(2,4-dimethoxy-phenyl)-furan-2-carbaldehydeSynthesized using method A. The compound did not need any further purification. 630.0 mg; 100% yield.MS (ES): UIz= 233 (M+H)+1H NMR (400 MHz, CDCI3, d ppm): 9.59 (s, 1 H), 7.98 (d, J = 8.7 Hz, 1 H), 7.31 (d, J = 3.7 Hz, 1 H), 7.00 (d, J = 3.7 Hz, 1 H), 6.60 (dd, J = 8.7, 2.3 Hz, 1 H), 6.53 (d, J = 2.3 Hz, 1 H), 3.94 (s, 3H), 3.87 (s, 3H). | |
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; toluene; at 90℃; | General procedure: To a solution of substituted phenylboronic acid (3.87 mmol) in toluene/ethanol (50/50, 40 mL), 5-bromofuran-2-alsehyde (600 mg, 3.43 mmol), potassium carbonate (947.96 mg, 6.86 mmol) aq. solution (10.3 mL water), and tetrakis(triphenyphosphine)palladium(0) (35.78 mg, 0.03 mmol) were added slowly, after which the reaction mixture was stirred at 90 C. The mixture was acidified by 6 N hydrogen chloride solution, and extracted with dichloromethane. The organic layer was washed with brine, dried (MgSO4) and, filtered. The solvent was concentrated under reduced pressure to yield compound 10, 5(4-carboxaminophenyl)furan-2-aldehyde. Yield 60%; 1H NMR (300 MHz, DMSO-d6) δ: 9.65 (s, 1H), 8.11 (s, 1H), 8.02-7.94 (m, 4H), 7.69 (d, J = 3.7 Hz, 1H), 7.50 (s, 1H), 7.42 (d, J = 3.7 Hz, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With piperidine; In pyridine; for 3.0h;Inert atmosphere; Reflux; | General Procedure: Piperidine was added to a solution of the appropriate aldehyde (4.97 mmol), malonic acid (5.96 mmol) and pyridine (10.94 mmol) under nitrogen atmosphere. The reaction mixture was heated to reflux under vigorous stirring for 3 hours, after which according to TLC the reaction was completed. The reaction mixture was allowed to cool and EtOAc (20 mL) was added, acidified to pH 5 with 1 M HCl, and the organic layer was sequentially washed with water, dried over MgSO4 and concentrated in vacuo. The pure desired product was obtained after purification by column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In ethanol; water; at 70℃;Inert atmosphere; Sealed tube; | General procedure: A bromo-aldehyde (1 mmol), boronic acid (1.1e1.3 mmol), tetrakis(triphenylphosphine)palladium (0.05 mmol), potassium carbonate(3 mmol), water (3 ml), ethanol (4 ml) and toluene (4 ml)were added to a round-bottomed flask. The reaction mixture wasflushed with argon, sealed under septa and heated at 70 C overnight.After cooling to room temperature, water (50 ml) was added,and product was extracted with ethyl acetate (3 x 50 ml). Combinedextracts were washed with brine, dried with anhydrousmagnesium sulfate and evaporated under reduced pressure. Theproduct was purified by column chromatography on silica withchloroform or a mixture of methanol and chloroform (1:9). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With n-butyllithium; In tetrahydrofuran; hexane; at -78℃; for 0.166667h; | Step 1: (5-Bromo-2-furyI)(4-chIoropyrimidin-5-yl)methanol [00984] A solution of <strong>[63558-65-6]4-chloro-5-iodopyrimidine</strong> (3.60 g, 14.80 mmol) in THF (40.0 mLl) was cooled to -78 C, at which point 2.50 M of n-BuLi in hexane (7.0 mL, 17.50 mmol) was added dropwise via syringe. At the conclusion of the addition, a solution of 5-bromo-2-furaldehyde (2.0 g, 1 1.40 mmol) in THF (10.0 mL) was next added dropwise, via syringe and the reaction was stirred at -78 C for 10 min. The reaction was quenched via addition of a saturated NaHC03 solution (20 mL), and then allowed to warm to RT and extracted with EtOAc (3X). Layers were separated and the combined organic layers were washed with brine, dried over Na2S04, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (eluting with 0-50% EtOAc/Hex. over 25 mins) to give 2.5 g (75%) of product. NMR (400 MHz, Chloroform-d) delta 9.04 (s, 1 H), 8.95 (s, 1H), 6.28 (d, J = 3.2 Hz, 1 H), 6.19 (d, / = 3.2 Hz, 1H),6.08 (s, 1 H), 3.38 (s, 1H). |
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