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Chemical Structure| 456-48-4 Chemical Structure| 456-48-4

Structure of 3-Fluorobenzaldehyde
CAS No.: 456-48-4

Chemical Structure| 456-48-4

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Jooste, Joelien ; Legoabe, Lesetja J ; Ilbeigi, Kayhan ; Caljon, Guy ; Beteck, Richard M ;

Abstract: Geraniol, a primary component of several essential oils, has been associated with broad-spectrum antiprotozoal activities, although moderate to weak. This study primarily concentrated on the synthesis of hydrazinated geraniol derivatives aspotential antiprotozoal agents. The synthesised compounds were tested in vitro against different parasitic protozoans of clinical relevance, including Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania infantum. Compounds 6, 8, 13, 14 and 15 demonstrated low micromolar activity against the different parasites. Compounds 8, 13, 14 and 15 had the highest efficacy against Trypanosoma brucei rhodesiense, as indicated by their respective IC50 values of 0.74, 0.56, 1.26 and 1.00 μM. Compounds 6, 14 and 15 displayed the best activity against Trypanosoma brucei brucei, with IC50 values of 1.49, 1.48 and 1.85 μM, respectively. The activity of compounds 6, 14 and 15 also extended to intracellular Trypanosoma cruzi, with IC50 values of 5.14, 6.30 and 4.90 μM, respectively. Compound 6, with an IC50 value of 11.73 μM, and compound 14, with an IC50 value of 8.14 μM, demonstrated some modest antileishmanial activity.

Keywords: geraniol ; Leishmania infantum ; Trypanosoma brucei brucei ; Trypanosoma brucei rhodesiense ; Trypanosoma cruzi

Purchased from AmBeed: ; ; ; ;

Agarwal, Devesh S. ; Beteck, Richard M. ; Ilbeigi, Kayhan ; Caljon, Guy ; Legoabe, Lesetja J. ;

Abstract: A library of imidazo[1,2-a]pyridine-appended chalcones were synthesized and characterized using 1H NMR,13C NMR and HRMS. The synthesized analogs were screened for their antikinetoplastid activity against Trypanosoma cruzi, Trypanosoma brucei brucei, Trypanosoma brucei rhodesiense and Leishmania infantum. The analogs were also tested for their cytotoxicity activity against human lung fibroblasts and primary mouse macrophages. Among all screened derivatives, (E)-N-(4-(3-(2-chlorophenyl)acryloyl)phenyl)imidazo[1,2-a]pyridine-2-carboxamide was found to be the most active against T. cruzi and T. b. brucei exhibiting IC50 values of 8.5 and 1.35 μM, resp. Against T. b. rhodesiense, (E)-N-(4-(3-(4-bromophenyl)acryloyl)phenyl)imidazo[1,2-a]pyridine-2-carboxamide was found to be the most active with an IC50 value of 1.13 μM. All synthesized active analogs were found to be non-cytotoxic against MRC-5 and PMM with selectivity indexes of up to more than 50.

Keywords: antikinetoplastid ; ; drug likeliness properties ; ; neglected tropical diseases (NTDs) ; Trypanosoma brucei brucei ; Trypanosoma brucei rhodesiense

Purchased from AmBeed: ; ; ; ; ; ; ; ; ; ; ; ; ; ; 1113-59-3

Michael B. Dybek ;

Abstract: Memantine, an N-methyl-D-aspartate receptor (NMDAR) antagonist is FDA approved for the treatment of moderate to severe Alzheimer disease. The efficacy is believed to stem from its ability to block/mitigate excitotoxicity that stems from excessive glutamatergic activation/transmission and is thus neuroprotective. However, they display tolerability issues that hinder their ability to be utilized as neuroprotective agents. Previous studies from our lab suggest that the compounds that function as uncompetitive NMDAR antagonists and have moderate affinity to the NMDAR demonstrate the best tolerability. This observation has prompted investigations for novel neuroprotective NMDAR antagonists with improved efficacy and tolerability. Our lead compounds phencyclidine (PCP) and analogs have demonstrated the ability to protect hippocampal neurons from NMDA insult in vitro. Our studies explored synthesizing and evaluating both arylalkylamines and 1,2-diarylethylamines. A total of 76 target compounds were synthesized as part of this exploration. In vitro competitive radio-ligand binding assays were conducted for each compound to determine affinities to NMDAR in rat forebrain homogenate. Several of these compounds demonstrated binding affinities within a previously defined target range (400 nM – 2,100 nM). This range was previously determined to provide the highest tolerability for uncompetitive NMDAR antagonists. 34 compounds were further evaluated to obtain binding affinities on 44 other relevant central nervous system targets. This SAR investigation has uncovered several intriguing polypharmacological profiles have emerged, including potent affinities to NMDAR, dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT).

Purchased from AmBeed: ; ; ;

Dylan Hart ; Lesetja J. Legoabe ; Omobolanle J. Jesumoroti ; Audrey Jordaan ; Digby F. Warner ; Rebecca Steventon , et al.

Abstract: Herein we report the synthesis of novel compounds inspired by the antimicrobial activities of nitroazole and thiazolidin-4-one based compounds reported in the literature. Target compounds were investigated in vitro for antitubercular, antibacterial, antifungal, and overt cell toxicity properties. All compounds exhibited potent antitubercular activity. Most compounds exhibited low micromolar activity against S. aureus and C. albicans with no overt cell toxicity against HEK-293 cells nor haemolysis against human red blood cells. Notably, compound 3b exhibited low to sub-micromolar activities against Mtb, MRSA, and C. albicans. 3b showed superior activity (0.25 μg/ml) against MRSA compared to vancomycin (1 μg/ml).

Purchased from AmBeed: ; ; ; ; ; ; ; ; ; ; 591-31-1 ; ; ; ; ; 123-08-0 ; 100-52-7 ; ; 89-98-5

Alternative Products

Product Details of [ 456-48-4 ]

CAS No. :456-48-4
Formula : C7H5FO
M.W : 124.11
SMILES Code : O=CC1=CC=CC(F)=C1
MDL No. :MFCD00003348
InChI Key :PIKNVEVCWAAOMJ-UHFFFAOYSA-N
Pubchem ID :68009

Safety of [ 456-48-4 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H225-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338
Class:3
UN#:1989
Packing Group:

Computational Chemistry of [ 456-48-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 31.79
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

17.07 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.42
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

1.75
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.06
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

1.88
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

2.42
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.91

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.14
Solubility 0.901 mg/ml ; 0.00726 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.73
Solubility 2.33 mg/ml ; 0.0188 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-2.58
Solubility 0.326 mg/ml ; 0.00262 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

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)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.81 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

2.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.0

Application In Synthesis of [ 456-48-4 ]

* 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 [ 456-48-4 ]

[ 456-48-4 ] Synthesis Path-Downstream   1~34

  • 1
  • [ 57497-39-9 ]
  • [ 456-48-4 ]
  • [ 139607-30-0 ]
  • 2
  • [ 456-48-4 ]
  • [ 7292-74-2 ]
  • 3
  • [ 2612-28-4 ]
  • [ 456-48-4 ]
  • [ 202476-48-0 ]
YieldReaction ConditionsOperation in experiment
With PTS; In toluene; Step 1 : 2-Propyl-1,3-propanediol (138.0 g; 1.17 mol) and 3-fluorobenzaldehyde (138.0 g; 1.11 mol) were dissolved in toluene (1.5 liters), and PTS (7 g) was added. The mixture was refluxed for 3 hours while being dehydrated with a Dean-Stark's device. The resultant reaction mixture was washed sequentially with saturated sodium bicarbonate solution and saturated brine, and then dried over magnesium sulfate. Subsequently, the solvent was evaporated. The residue was recrystallized twice from heptane, to thereby obtain 81.2 g (362 mmol) of 5-propyl-2-(3-fluorophenyl)-1,3-dioxane. The yield of the compound from 3-fluorobenzaldehyde was 32.6%.
  • 4
  • [ 120-35-4 ]
  • [ 456-48-4 ]
  • 4-Methoxy-3-(3-fluoro-benzylamino)-N-phenyl-benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Example 214 4-Methoxy-3-(3-fluoro-benzylamino)-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-fluorobenzaldehyde as starting materials, which are commercially available from Aldrich; m.p. 137-140 C.
  • 5
  • [ 26215-14-5 ]
  • [ 456-48-4 ]
  • [ 1042317-53-2 ]
  • 6
  • [ 106518-84-7 ]
  • [ 17115-51-4 ]
  • [ 456-48-4 ]
  • [ 1265632-10-7 ]
YieldReaction ConditionsOperation in experiment
63% at 90℃; for 12h;Neat (no solvent); Aldehyde 1 (1 mmol), dihydrothiophen-3(2H)-one-1,1-dioxide 2 (0.134 g, 1 mmol), enaminone 3 (1 mmol) and were triturated together in an agate mortar for 5 minutes. Then the mixture was kept at 90 C for a certain time (monitored by TLC). The result mixture was washed with water and recrystallized from ethanol (95 %) to give pure product 4.
  • 7
  • [ 17115-51-4 ]
  • [ 18940-21-1 ]
  • [ 456-48-4 ]
  • [ 1265631-93-3 ]
YieldReaction ConditionsOperation in experiment
85% at 90℃; for 8h;Neat (no solvent); Aldehyde 1 (1 mmol), dihydrothiophen-3(2H)-one-1,1-dioxide 2 (0.134 g, 1 mmol), enaminone 3 (1 mmol) and were triturated together in an agate mortar for 5 minutes. Then the mixture was kept at 90 C for a certain time (monitored by TLC). The result mixture was washed with water and recrystallized from ethanol (95 %) to give pure product 4.
  • 8
  • [ 17115-51-4 ]
  • [ 24706-47-6 ]
  • [ 456-48-4 ]
  • [ 1265632-11-8 ]
YieldReaction ConditionsOperation in experiment
65% at 90℃; for 12h;Neat (no solvent); Aldehyde 1 (1 mmol), dihydrothiophen-3(2H)-one-1,1-dioxide 2 (0.134 g, 1 mmol), enaminone 3 (1 mmol) and were triturated together in an agate mortar for 5 minutes. Then the mixture was kept at 90 C for a certain time (monitored by TLC). The result mixture was washed with water and recrystallized from ethanol (95 %) to give pure product 4.
  • 9
  • [ 17115-51-4 ]
  • [ 36646-78-3 ]
  • [ 456-48-4 ]
  • [ 1265632-04-9 ]
YieldReaction ConditionsOperation in experiment
86% at 90℃; for 9h;Neat (no solvent); Aldehyde 1 (1 mmol), dihydrothiophen-3(2H)-one-1,1-dioxide 2 (0.134 g, 1 mmol), enaminone 3 (1 mmol) and were triturated together in an agate mortar for 5 minutes. Then the mixture was kept at 90 C for a certain time (monitored by TLC). The result mixture was washed with water and recrystallized from ethanol (95 %) to give pure product 4.
  • 10
  • [ 17115-51-4 ]
  • [ 105-56-6 ]
  • [ 456-48-4 ]
  • [ 1338580-14-5 ]
  • 11
  • [ 17115-51-4 ]
  • [ 109-77-3 ]
  • [ 456-48-4 ]
  • [ 1338579-98-8 ]
  • 12
  • [ 456-48-4 ]
  • [ 723284-79-5 ]
  • 13
  • [ 456-48-4 ]
  • [ 403-54-3 ]
  • [ 455-37-8 ]
  • 14
  • [ 456-48-4 ]
  • [ 97682-44-5 ]
  • 15
  • [ 5676-56-2 ]
  • [ 456-48-4 ]
  • C15H9BrFNO [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-benzyl-N,N,N-triethylammonium chloride; sodium hydroxide; In dichloromethane; water;Inert atmosphere; General procedure: The SBOs were prepared by the base-catalysed condensation of the appropriate 5-halogeno-2-methylbenzoxazole with the requisite aromatic aldehyde under phase transfer conditions. In a typical experiment, equimolar quantities (5 mmol) of the starting materials were dissolved in dichloromethane (20-50 ml) in the presence of benzyltriethylammonium chloride (3 mmol) and stirred magnetically under a nitrogen atmosphere as an aqueous solution of sodium hydroxide (50%, w/v, 5 ml) was added dropwise over a period of 10 min. After being stirred for 2-36 h until analytical thin layer chromatography indicated that the reaction was complete, the mixture was diluted with water (50 ml) and the SBO was extracted with dichloromethane (3×20 ml), dried (MgSO4), filtered, evaporated under reduced pressure and recrystallized from aqueous methanol or ethanol.
  • 16
  • [ 14447-15-5 ]
  • nitenpiram [ No CAS ]
  • [ 456-48-4 ]
  • [ 1443754-05-9 ]
  • 17
  • [ 14447-15-5 ]
  • [ 456-48-4 ]
  • C13H12FNO2 [ No CAS ]
  • 18
  • [ 14447-15-5 ]
  • [ 456-48-4 ]
  • C24H27ClFN5O4 [ No CAS ]
  • 19
  • [ 15862-94-9 ]
  • [ 456-48-4 ]
  • [ 1584706-35-3 ]
YieldReaction ConditionsOperation in experiment
85% General procedure: All materials were dried for one day at 120 C. Chloride and carbonyl derivatives were introduced into a Schlenk of 30 mL. Products were put in vacuo, then under nitrogen. An appropriate volume of anhydrous DMF was added after 10 min of nitrogen bubbling. The solution was vigorously stirred for 20 min at -20 C. TDAE was added slowly under inert atmosphere. The reaction was stirred for one hour. The second reaction phase was performed at rt or at temperature according to procedure of synthesis. The reaction was hydrolysed with distilled water after TLC analysis clearly showed that the chloride 1 had been totally consumed. The aqueous solution was extracted with dichloromethane and the combined organic layers washed with brine then dried on MgSO4.
  • 20
  • [ 456-48-4 ]
  • [ 455-37-8 ]
YieldReaction ConditionsOperation in experiment
21% General procedure: Under an argon atmosphere, liquid NH3 (25 mL) was condensedin a two-neck round-bottom flask immersed in a dry ice coolingbath and equipped with a dry ice reflux condenser. Aldehyde(7.34 mmol) was added, and the resulting solution (or suspension)was stirred for 1 h. KMnO4 (7.34 mmol, 1.16 g) was added,the cooling bath was removed, and the reaction mixture wasstirred for another hour with gentle reflux of NH3. Na2SO3 (22.0mmol, 2.78 g) was added, the reflux condenser was removed,and the NH3 was allowed to evaporate spontaneously. The darkbrownresidue was treated with 6 M HCl (30 mL), and theresulting precipitate was filtered, washed with H2O (100 mL)and sat. aq NaHCO3 (20 mL). All products were recrystallizedfrom EtOH.
21% General procedure: Under an argon atmosphere, liquid NH3 (25 mL) was condensedin a two-neck round-bottom flask immersed in a dry ice coolingbath and equipped with a dry ice reflux condenser. Aldehyde (7.34 mmol) was added, and the resulting solution (or suspension)was stirred for 1 h. KMnO4 (7.34 mmol, 1.16 g) was added,the cooling bath was removed, and the reaction mixture wasstirred for another hour with gentle reflux of NH3. Na2SO3 (22.0mmol, 2.78 g) was added, the reflux condenser was removed,and the NH3 was allowed to evaporate spontaneously. The darkbrownresidue was treated with 6 M HCl (30 mL), and theresulting precipitate was filtered, washed with H2O (100 mL)and sat. aq NaHCO3 (20 mL). All products were recrystallizedfrom EtOH.
  • 21
  • [ 57497-39-9 ]
  • [ 456-48-4 ]
  • [ 139607-30-0 ]
  • 22
  • [ 39549-79-6 ]
  • [ 456-48-4 ]
  • 2-(3-fluorophenyl)-7-methylquinazolin-4(3H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% With sodium hydrogensulfite; In N,N-dimethyl acetamide; at 150℃; General procedure: Sodium hydrogen sulfite (4 mmol) was added to a solution of anthranilamide 1 (2 mmol) and benzaldehyde 2 (2 mmol) in N,N- dimethylacetamide (5 mL). The mixture was heated under continuous stirring at 150 o C for 2-3 h and poured into ice water. The precipitate was then filtered, washed with water followed byethanol, and dried to yield the 2-arylquinazolinones 3-31.#10;#10;
  • 23
  • [ 347174-05-4 ]
  • [ 456-48-4 ]
  • ethyl 4-(cyclohexylamino)-3-(3-fluorobenzylamino)benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: SI, Figure 4. General procedure of the reductive amination reactions: synthesis of AA9-AA24 compounds (Tables 1 and 2). The <strong>[347174-05-4]ethyl 3-amino-4-(cyclohexylamino)benzoate</strong> (AA1) and derivatives (1 equiv.)and benzaldehyde (1 equiv) were heated in DCE for 1h at 80 oC in the presence of molecular sieves (4 A), then the mixture was cooled down to room temperature before addition of the NaBH(OAc)3 (1.6 equiv.) in small portions over 3h. The reaction mixture was stirred at room temperature under a nitrogen atmosphere for 17h. The reaction mixture was quenched with aqueous saturated NaHCO3, and the product was extracted with EtOAc. The EtOAc extract was dried (MgSO4), and the solvent was evaporated. The residue was purified by flash-column chromatography on silica gel, using a mixture of solvent of DCM: MeOH (50:1), to provide the desired AA9-AA24 compounds (Tables 1-2).
  • 24
  • [ 141-82-2 ]
  • [ 456-48-4 ]
  • [ 19883-77-3 ]
  • 25
  • [ 456-48-4 ]
  • [ 19883-77-3 ]
  • 26
  • [ 456-48-4 ]
  • (R)-3-amino-3-(3-fluoro-phenyl)-propionic acid [ No CAS ]
  • [ 20595-30-6 ]
  • [ 19883-77-3 ]
  • 27
  • [ 456-48-4 ]
  • (R)-3-amino-3-(3-fluoro-phenyl)-propionic acid [ No CAS ]
  • [ 723284-79-5 ]
  • [ 20595-30-6 ]
  • [ 19883-77-3 ]
  • 28
  • [ 54396-44-0 ]
  • [ 868-85-9 ]
  • [ 456-48-4 ]
  • dimethyl (3-fluorophenyl)(2-methyl-3-(trifluoromethyl)phenylamino)methylphosphonate [ No CAS ]
YieldReaction ConditionsOperation in experiment
97% With chitosan; In neat (no solvent); at 75℃; for 0.0833333h;Microwave irradiation; Green chemistry; General procedure: An equimolar mixture of <strong>[54396-44-0]2-methyl-3-(trifluoromethyl)aniline</strong> (0.351 g, 0.002 mol), corresponding aldehyde (0.002 mol), dimethyl phosphite (0.18 ml, 0.002 mol) and chitosan catalyst (10 molpercent) were taken in a reaction glass tube, degassed for 10 min and microwave irradiated at 180 W for 2 min at 60 °C. The progress of the reaction was monitored by TLC using petroleum ether and ethyl acetate (3:7) as solvent. After completion of the reaction, the mixture was diluted with ethyl acetate, washed with water (2 x 15 ml) followed by brine (1 x 10 ml), dried over Na2SO4 and evaporated to dryness. The crude mass was purified by column chromatography on silicagel (100-200 mesh) by using a 7:3 mixture of ethyl acetate in hexane to afford the pure alpha-aminophosphonates.
  • 29
  • [ 1986-47-6 ]
  • [ 456-48-4 ]
  • (1S*,2R*)-N-(3-fluorobenzyl)-2-phenylcyclopropan-1-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
39% 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.
  • 30
  • [ 13338-63-1 ]
  • [ 456-48-4 ]
  • (Z)-2-(3,4,5-trimethoxyphenyl)-3-(3-fluorophenyl)acrylonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
40.4% With sodium methylate; In methanol; at 60℃; Using the method of synthesizing an intermediate similar to that of Example 1,Take <strong>[13338-63-1]3,4,5-trimethoxyphenylacetonitrile</strong> (5) 0.01 mol, 0.01 mol of 3-fluorobenzaldehyde and 20 mL of methanol into a 50 mL three-necked flask.Stirring to 60 C, adding 0.005 mol of sodium methoxide, constant temperature reaction 4-6 h,TLC scanning and detection, after the reaction is completed, it is cooled to room temperature, filtered, washed with water, dried, and recrystallized from methanol to obtain a pale yellow solid.Yield: 40.4%,
  • 31
  • [ 456-48-4 ]
  • [ 703-67-3 ]
  • 32
  • [ 1004-38-2 ]
  • [ 20356-45-0 ]
  • [ 456-48-4 ]
  • 2,4-diamino-5-(3-fluorophenyl)-7-(1H-indol-3-yl)-5,8-dihydropyrido[2,3-d]pyrimidine-6-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With indium(III) chloride; In ethanol; at 120℃; for 0.166667h;Microwave irradiation; General procedure: A mixture of <strong>[1004-38-2]2,4,6-triaminopyrimidine</strong> 1 (1.0 mmol), 3-(2-cyanoacetyl)indole 2 (1.0 mmol), appropriate aromatic aldehyde (1.0 mmol) and indium chloride (0.05 mmol) in ethanol (5.0 mL) were subjected to microwave irradiation for 10 min at 120 C. After completion of the reaction (monitored by TLC using a dichloromethane-ethanol (9:1) mixture as the mobile phase), the reaction mixture was cooled and filtered. The solid product obtained was initially washed with ethanol, and finally recrystallized from ethanol.
  • 33
  • [ 28710-97-6 ]
  • [ 456-48-4 ]
  • (3aR*,4S*,8aR*,9S*)-4,9,11-tris(3-fluorophenyl)-2,7-diphenyl-5,7,9,10-tetrahydro-3a,8a-methanodipyrazolo[3,4-b:3',4'-f][1,5]diazocine-3,8(2H,4H)-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With toluene-4-sulfonic acid; In methanol; for 4.0h;Reflux; General procedure: p-Toluenesulfonic acid (PTSA) (0.1mmol, 10mol%) was added to a mixture of aminopyrazolone 1 (1mmol) and benzaldehyde 2a (2.5mmol) in methanol (5mL) and the mixture was stirred at reflux for 4h. Upon reaction completion (TLC), the solvent was removed under reduced pressure and the residue purified by silica gel column chromatography (n-hexane/EtOAc, 3:1). (3aR*,4S*,8aR*,9S*)-2,4,7,9,11-Pentaphenyl-5,7,9,10-tetrahydro-3a,8a-methanodipyrazolo[3,4-b:3?,4?-f][1,5]diazocine-3,8(2H,4H)-dione (3a).
  • 34
  • [ 405939-39-1 ]
  • [ 456-48-4 ]
  • tert-butyl 4-bromo-5-((3-fluorophenyl)(hydroxy)methyl)thiazol-2-ylcarbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% To a solution of lithium diisopropylamide (16.5 ml_, 33 mmol) in tetrahydrofuran (20 ml_) at 0 C was added ferf-butyl 5-bromothiazol-2-ylcarbamate (2.8 g, 10.0 mmol) slowly under argon. The reaction mixture was stirred at 0 C for 30 minutes before a solution of 3-fluorobenzaldehyde (4.1 g, 33.0 mmol) in tetrahydrofuran (1 0 ml_) was added. The reaction solution was warmed to room temperature and stirred for 20 h. The reaction mixture was diluted with water (30 ml_) and extracted with ethyl acetate (150 ml_ x 3). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography (silica gel, petroleum ether/ethyl acetate = 4/1 ) to give ferf-butyl 4-bromo-5-((3-fluorophenyl)(hydroxy)methyl)thiazol-2-ylcarbamate as a yellow solid (2.5 g, 6.2 mmol, 62%). LCMS (ESI) m/z: 346.9 [M-56+H]+.
 

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