An Efficient Synthesis of Selective Human NR2A Antagonist NVP-AAM077

A short and efficient synthesis of the selective human N-methyl-D-aspartate （NMDA） receptor 2A （NR2A） antagonist NVP-AAM077 is described. The target was achieved in 8 steps and in 54% overall yield from the commercially available chemical 3-methylbenzene-1,2-diamine. A NaIO4/DMF-based oxidation of the bromide to corresponding aldehyde and an addition of phosphinic acid ester to the aldimine successfully served as the key steps.     

The aza Arndt–Eistert reaction based on N-trifluoromethylsulfonylarenecarboximidoyl chlorides

The aza analogues of carboxylic acids chlorides containing the NSO₂CF₃ and NSO₂CH₃ groups instead of oxygen atom were used in the Arndt–Eistert reaction. It was found that N-trifluoromethylsulfonyl-(4-fluorophenyl)-carboximidoyl chloride 1 reacts with diazomethane vigorously even at ?70 °C with formation of 1-trifluoromethylsulfonylamino-2-(4-fluorophenyl)-2,3-dimorpholine-4-yl-propane 3, 2-trifluoromethylsulfonylamino-2-(4-fluorobenzyl)-7-oxa-4-azonia-spiro[3.5]nonane 4, 2-trifluoromethylsulfonylamino-2-(4-fluorobenzyl)-1,3-dimorpholine-4-yl-propane 5 and 1-trifluoromethylsulfonylamino-2-(4-fluorobenzyl)-2,3-dimorpholine-4-yl-propane 6. Reaction of N-methylsulfonylbenzcarboximidoyl chloride 8 with diazomethane proceeds at ?15 °C yielding 4-chloro-4-methylsulfonylaminomethyl-3-phenyl-4,5-dihydro-1H-pyrazoline 9.     

Thermal Arndt–Eistert Reactions of N‐Tosyl Cyclic α‐Amino Acids

Thermal Arndt–Eistert reactions of N‐tosyl cyclic α‐amino acids were studied to explore the preparation of α,β‐unsaturated esters bearing a terminal tosylamino group. For L‐N‐tosyl‐aziridine 2‐carboxylic acid and L‐N‐tosyl‐azetidine 2‐carboxylic acid, the corresponding (E)‐α,β‐unsaturated esters were obtained stereospecifically.     

Concise Synthesis of JN403, a Novel Nicotinic Acetylcholine Receptor α7 Selective Agonist

A three-step method for the synthesis of (S)-(1-aza-bicyclo[2.2.2]oct-3-yl)carbamic acid (S)-1-(2-fluorophenyl)ethyl ester HCl salt (12) was developed, starting from alcohol 3 and resulting in an overall yield of 50%. A key feature of the present study is the need to use a strong base such as n-butyllithium for neutralizing the HCl salt of 5 during the condensation of 4 with 5.     

Yuanhuacin A Is a Selective Antagonist of Phorbol Ester Receptor in Protein Kinase C

Protein kinase C with a molecular weight of 82 kD has been purified to electrophoresis homogenous from rat brain through a series of chromatography columns including DE-52, Sepharose G-200 and phenyl-Sepharose. The enzyme possessed autophosphorylation activity. Yuanhuacin A inhibited the ~3H-phorbol-12, 13-dibutyrate (~3H-PdBu) binding of PKC with an IC_(50) value of 1.48±0.28×10~(-8) mol/L when the concentration of ~3H-PdBu was 1.5×10~(-9) mol/L (K_i=1.2×10~(-8) mol/L). Yuanhuacin A inhibited the PdBu-stimulated PKC activity in the catalysis of the phosphorylation of Histone Ⅲ-S with an IC_(50) of 2.82±0.37×10~(-9) mol/L (PdBu=10~(-6) mol/L), while it had no effect on the basal and Ca~(2+)-stimulated PKC activity in the same assay system. This result suggests that Yuanhuacin A is a selective antagonist of the phorbol ester receptor in protein kinase C.     

Practical Synthesis of p‐Aminophenethylspiperone (NAPS), a High‐Affinity,Selective D2‐Dopamine Receptor Antagonist

Because attempts to scale up the published synthetic preparation of p‐aminophenethylspiperone (NAPS) by N‐alkylation of spiperone with 4‐nitrophenethyl bromide followed by reduction gave poor yields and difficulties during purification, an alternative synthetic approach has been developed. Use of 4‐(N‐tert‐butyloxycarbonyl) aminophenethyl bromide to alkylate spiperone followed by the Boc group deprotection gave NAPS in 56% yield. This procedure provides an improved and efficient synthesis of the important high‐affinity, selective D₂‐dopamine receptor antagonist NAPS.     

Stereoselective Synthesis of the Optical Isomers of a New Muscarinic Receptor Antagonist,HL‐031120

We present here a practical stereoselective synthetic method to produce enantiopure isomers of a new muscarinic receptor antagonist, HL‐031120 (3‐quinuclidinyl‐2′‐cyclopentyl‐2′‐hydroxy‐2′‐phenylacetate, I). Four optical isomers were effectively by stereoselective synthesized using pivaldehyde as steric hindrance agent from the chiral starting material, (S) or (R)‐mandelic acid. The isomers were obtained with 70–76% yields in 98–99% e.e.     

Efficient Synthesis of the Cl- C7 Fragment of Didemnaketal A

The stereoselective synthesis of the C1-C7 fragment (3R,4S,6R)-3,4-di[(tert-butyl-dimethylsilyl)oxy]-7-hydroxy-6-methylheptan-2-one, which is the crucial intermediate for synthesis of the HIV-1 protease inhibitive didemnaketals, was developed via 12 steps from the natural (+)-pulegone.     

Zinc Hydroxyapatite–Catalyzed Efficient Synthesis of 5‐Substituted 1H‐Tetrazoles

Zinc hydroxyapatite (ZnHAP) is an effective heterogeneous catalyst for the (2+3)‐cycloaddition of sodium azide with nitriles to afford 5‐substituted 1H‐tetrazoles in good yields. The catalyst is recovered and reused for several cycles with consistent activity.     

Efficient Synthesis of the C1-C7 Fragment of Didemnaketal A

The stereoselective synthesis of the CI-C7 fragment (3R,4S,6R)-3,4-di[(tert-butyldimethylsilyl)oxy]-7-hydroxy-6-methylheptan-2-one, which is the crucial intermediate for synthesis ofthe HIV-1 protease inhibitive didemnaketals, was developed via 12 steps from the natural ( )-pulegone.     

Synthesis of the Neurokinin 1 Receptor Antagonist (+)-L-733,060 by Jacobsen’s Hydrolytic Kinetic Resolution

Russian Journal of Organic Chemistry - Enantioselective synthesis of the neurokinin 1 receptor antagonist (+)-L-733,060 has been achieved using Jacobsen’s hydrolytic kinetic resolution...     

Efficient Continuous-Flow Synthesis and Evaluation of Anticancer Activity of Novel Quinoline–Pyrazoline Derivatives

Russian Journal of Organic Chemistry - An efficient and simple continuous-flow synthetic protocol for novel quinoline-tethered pyrazoline derivatives, which involves condensation of...     

Efficient Synthesis of a New Type of Baylis–Hillman Adducts and Their Stereoselective Bromination

A new type of Baylis–Hillman adducts derived from chlorovinyl aldehydes were prepared via Vilsmeier reaction of ketones with a bis(trichloromethyl) carbonate (BTC)/DMF system to construct chlorovinyl aldehydes, followed by sonochemical Baylis–Hillman reaction under solvent-free conditions. The stereoselective bromination of these new compounds with a Br₂-Ph₃P system has been achieved efficiently with good to excellent yields under mild conditions.     

Stannic Chloride–Iodine: An Efficient Reagent for Regioselective Synthesis of Furan–Fused Heterocycles

SnCl₄‐I₂‐mediated cyclization of ortho‐cyclohexenyl phenol and ortho‐cyclohexenyl enol derivatives of coumarin, uracil, dimedone, and pyrone at room temperature for 1 h give the linear cyclized products in 78–90% yield, which, on treatment with 10% Pd‐C at 250°C for 1–2 h, afford corresponding aromatized products in 80–84% yield.     

Highly Efficient Microwave‐Assisted Synthesis of Subphthalocyanines

A novel, highly efficient, single‐step synthesis of subphthalocyanines using microwave irradiation of phthalonitrile and boron trichloride in 1‐chloronaphthalene was accomplished for the first time. This provides a new preparative method for the synthesis of subphthalocyanines with reduced reaction times and improved yields.     

An Efficient Solid-State Synthesis of N-Aryl-2-phenyldiazenecarboxamides

The subject of organic solid-state synthesis is a fascinating one. It has many advantages such as high efficiency and selectivity, easy separation and purification, mild reaction conditions, and environmental acceptability1. In recent years, this method has been widely used in a variety of organic reactions including substitution2, condensation3, oxidation-reduction4, rearrangement5 and elimination6. However, the solid state reaction using K3Fe(CN)6/KOH to oxidize substituted semicarbazides…     

An Efficient Synthesis of (±)-Cycloillicinone

An efficient synthesis of (±)-cycloillicinone was accomplished in five steps from sesamol. The title compound was obtained via a biomimetic Diels–Alder cycloaddition between illicinone A and β-trans-ocimene as the key step.     

Efficient One-Pot Synthesis of β-Unsaturated Isoxazol-5-ones and Pyrazol-5-ones Under Ultrasonic Irradiation

4-Arylmethylidene-3-isopropylisoxazol-5-ones and 4-arylmethylidene-1-phenyl-3-isopropylpyrazol-5-ones have been prepared from the reactions of hydroxylamine and phenylhydrazine with methyl 4-methyl-3-oxovalerate and aromatic aldehydes in an aqueous medium at room temperature in the presence of pyridine under ultrasonic irradiation. The simple and facile method produced products in good yields.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

Highly Efficient Synthesis of 3,5-Diaryl-1,2,4-thiadiazoles in Water–Wet Paste Conditions

1,3-Dibromo-5,5-diphenylimidazolidine-2,4-dione (N,N’-dibromo phenytoin) was efficiently used for the rapid conversion of thiobenzamides to the corresponding 3,5-diaryl-1,2,4-thiadiazoles in water–wet paste conditions.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.