Structure of 3,4-Difluorobenzaldehyde
CAS No.: 34036-07-2
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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. : | 34036-07-2 |
| Formula : | C7H4F2O |
| M.W : | 142.10 |
| SMILES Code : | C1=C(C=CC(=C1F)F)C=O |
| MDL No. : | MFCD00010328 |
| InChI Key : | JPHKMYXKNKLNDF-UHFFFAOYSA-N |
| Pubchem ID : | 588088 |
| GHS Pictogram: |
|
| Signal Word: | Warning |
| Hazard Statements: | H227-H315-H319-H335 |
| Precautionary Statements: | P210-P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P370+P378-P362+P364-P403+P233-P501 |
| Num. heavy atoms | 10 |
| Num. arom. heavy atoms | 6 |
| Fraction Csp3 | 0.0 |
| Num. rotatable bonds | 1 |
| Num. H-bond acceptors | 3.0 |
| Num. H-bond donors | 0.0 |
| Molar Refractivity | 31.75 |
| TPSA ? Topological Polar Surface Area: Calculated from |
17.07 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.41 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.88 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.62 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.32 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.82 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.21 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-2.28 |
| Solubility | 0.74 mg/ml ; 0.00521 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-1.86 |
| Solubility | 1.96 mg/ml ; 0.0138 mol/l |
| Class? Solubility class: Log S scale |
Very soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.88 |
| Solubility | 0.188 mg/ml ; 0.00132 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 |
-5.83 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 |
2.0 |
| 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) |
1.03 |
* 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 |
|---|---|---|
| In nitrobenzene; at 160℃; for 26h; | 1.00 g 2,3-diamino-5-nitro-pyridine and 0.95 g 3,4-difluorobenzaldehyde were stirred in 60 ml nitrobenzene at 160 C for 26 hrs. The solvent was removed under vacuum and the residue dissolved in 40 ml pyridine at 60 C. The solution was cooled in an ice bath. Precipitated product was isolated by filtration and dried to yield 0.5 g of the title product. | |
| In nitrobenzene; at 160℃; for 26h; | Example 10-1 [2-(3,4-Difluoro-phenyl)-3H-imidazo[4,5-b]pyridin-6-yl]-carbamic acid isopropyl ester a) 2-(3,4-Difluoro-phenyl)-6-nitro-3H-imidazo[4,5-b]pyridine; 1.00 g 2,3-diamino-5-nitro-pyridine and 0.95 g 3,4-difluorobenzaldehyde were stirred in 60 ml nitrobenzene at 160 C. for 26 hrs. The solvent was removed under vacuum and the residue dissolved in 40 ml pyridine at 60 C. The solution was cooled in an ice bath. Precipitated product was isolated by filtration and dried to yield 0.5 g of the title product. |

[ 28785-06-0 ]
[ 34036-07-2 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With sodium hydrogencarbonate; triethylamine; In ethanol; dichloromethane; | (Example 4) Synthesis of 1-(3,4-difluorobenzylidene)-2-(4-propylbenzylidene)hydrazine (Compound No. 7 set forth in Table 1) To 40 g of a monohydrate of hydrazine was added a solution of 10 g of <strong>[28785-06-0]4-propylbenzaldehyde</strong> in 50 m of ethanol. The mixture was stirred at room temperature for 30 minutes. To the mixture was then added 150 m of saturated aqueous solution of sodium bicarbonate. To the mixture was then added 100 m of dichloromethane. The mixture was then washed with 150 m of saturated aqueous solution of sodium bicarbonate twice. To the resulting organic phase was then added 5 m of triethylamine. The mixture was then dehydrated and dried over anhydrous sodium sulfate. The solvent was then distilled off under reduced pressure. To the residue was then added 5 m of triethylamine. To the mixture were then added 50 m of ethanol and 8.5 g of 3,4-difluorobenzaldehyde. The mixture was then stirred at room temperature for 6.5 hours. To the mixture was then added 150 m of saturated aqueous solution of sodium bicarbonate. To the mixture was then added 100 m of dichloromethane. The mixture was then washed with 150 m of saturated aqueous solution of sodium bicarbonate twice. The solvent was then distilled off under reduced pressure. The residue was purified through alumina (basic) column chromatography (dichloromethane), and then recrystallized from methanol to obtain 5.7 g of 1-(3,4-difluorobenzylidene)-2-(4-propylbenzylidene)hydrazine. The compound thus obtained had a melting point of 50°C and exhibited nematic phase up to 59.5°C. The foregoing procedure was followed except that 4-methylbenzaldehyde, 4-ethylbenzaldehyde, 4-butylbenzaldehyde, 4-pentylbenzaldehyde, 4-heptylbenzaldehyde or 4-methoxybenzaldehyde was used instead of <strong>[28785-06-0]4-propylbenzaldehyde</strong>. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Example 274 3-(3,4-Difluoro-benzylamino)-4-methoxy-N-phenyl-benzamide The title compound has been made using the procedure of Example 50, but using 3-amino-4-methoxy-N-phenyl benzamide and 3,4-difluorobenzaldehyde as starting materials, which can be purchased from Aldrich; m.p. 150-152 C. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Methyltriphenylphosphonium bromide (251.31 g, 0.7037 mol), l,8-diazabicyclo[5.4.0]undec- 7-ene (117.84 g, 0.7741 mol) and toluene (250 ml) were taken into a clean and dry reaction assembly. The resulting mixture was heated at 40-45C, followed by stirring for 30 minutes. 3,4-Difluorobenzaldehyde (50 g, 0.3518 mol) was slowly added to the hot solution and the reaction mixture was heated at reflux temperature, followed by maintaining for 5 hours at reflux. After completion of the reaction, the mass was cooled to 25-30C, followed by washing with water (2 x 250 ml). The resulting mass was distilled under reduced pressure while maintaining the temperature at below 50C to give 3,4-difiuorostyrene. | ||
| Example 1 Preparation of 3,4-Difluorostyrene Methyltriphenylphosphonium bromide (71 g, 0.2111 mol), 1,8-diazabicyclo[5.4.0]undec-7-ene (35.37 g, 0.2311 mol) and toluene (75 ml) were taken into a clean and dry reaction assembly. The resulting mixture was heated at 40-45 C., followed by stirring for 30 minutes. 3,4-Difluorobenzaldehyde (15 g, 0.1055 mol) was slowly added to the above hot solution and the reaction mixture was heated at reflux temperature, followed by maintaining for 6 hours at reflux. After completion of the reaction, the mass was cooled to 25-30 C., followed by washing with water (2*250 ml). The resulting mass was distilled under reduced pressure while maintaining the temperature at below 50 C. to give 3,4-difluorostyrene. | ||
| General procedure: To a stirred suspension of methyltriphenylphosphonium bromide (1.61 g, 4.51 mmol, 1.5 equiv.)in 10 mL dry THF at -78 C under argon atmosphere, n-butyllithium (2.8 mL, 4.51 mmol, 1.6 Msolution in THF, 1.5 equiv.) was added dropwise. The yellow solution was allowed to stir for 15min. before addition of the 3,4 dimethoxybenzadehyde 5a (0.5 g, 3 mmol, 1 equiv.) in 5 mL dryTHF, upon which, the mixture turned white or pale yellow. After 2 h (or observed completion ofthe reaction by TLC), saturated ammonium chloride was added and the mixture extracted withCH2Cl2. The combined organic extracts were then dried (Na2SO4), and concentrated in vacuo. Evaporation of the solvent under reduced pressure gave the crude product. Purification by flashcolumn chromatography (Silica gel 230-400 mesh, 1-10% ethyl acetate/ petroleum ether)afforded the desired styrene 6a as a colorless liquid. |
[ 40800-65-5 ]
[ 34036-07-2 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 83% | In ethanol; for 18h;Reflux; | Step 1. Synthesis of ethyl 4-[(3,4-difluorophenyl)methylidene]amino}-3-methylbenzoate A solution of <strong>[40800-65-5]ethyl 4-amino-3-methylbenzoate</strong> (0.706 g, 3.94 mmol) and 3,4-difluorobenzaldehye (1.00 mL, 9.08 mmol) in ethanol (10 mL) was stirred at reflux for 18 h and cooled to room temperature. The crude was washed with diethyl ether/n-hexane (1:20) to give ethyl 4-[(3,4-difluorophenyl)methylidene]amino}-3-methylbenzoate (0.986 g, 83%) as an orange solid. 1H NMR (CDCl3, 400 MHz) delta 8.28 (s, 1H), 7.91-7.81 (m, 3H), 7.62-7.59 (m, 1H), 7.31-7.27 (m, 1H), 6.91 (d, 1H), 4.38 (q, 2H), 2.36 (s, 3H), 1.40 (t, 3H). |
[ 34036-07-2 ]
[ 1986-47-6 ]
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 37% | General procedure: Trans-2-phenylcyclopropylamine hydrochloride (1.0 eq.), acetic acid (1.0eq.) and the appropriate aldehyde (0.9 eq.) were dissolved in around bottom flask in 10 mL dry DCE. The reaction mixture was stirred gently at room temperature for 2 h before sodium triacetoxyborohydride (3.0 eq.) was added in small portions to the reaction vessel. The reaction was monitored by TLC and quenched using 10 mL of an aqueous (5%) NaHCO3 solution. The organic layer was separated and the aqueous layer extracted three times with10 mL of DCE. All organic layers were combined, dried over anhydrous Na2SO4, concentrated in vacuo and purified using flash chromatography (silica gel; cyclohexane/ethyl acetate) to give the desired compound. |

[274693-55-9]
2-(((3aR,4S,6R,6aS)-6-Amino-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)oxy)ethanol