35739-70-9

Upstream product

• 917-54-4 methyllithium 
• 7550-45-0 titanium tetrachloride 
• 7440-32-6 titanium 
• 74-87-3 methylene chloride 
• 544-97-8 dimethyl zinc(II) 
• 19289-17-9 TiCl₄*1,2-DME 

Downstream Products

• 62469-66-3 4,4-dimethyl-4,5,6,7-tetrahydro-benzo[b]thiophene 
• 5980-96-1 1-isopropyl-2,4,6-trimethylbenzene 
• 33429-72-0 2-chloro-4,4-dimethylpentane 
• 40960-66-5 rac-(2R,3R)-3-phenylbutan-2-ol 
• 56907-39-2 rac-(2R,3S)-3-phenylbutan-2-ol 
• 106543-70-8 2,2,4,4,6,6,8,8-Octamethyl-3,7-dioxabicyclo<3.3.0>oct-1(5)-en 
• 54750-40-2 1-(1,2-dimethylcyclopent-2-en-1-yl)-4-methylbenzene 
• 16982-00-6 1-(1,2,2-trimethylcyclopentyl)-4-methylbenzene 
• 594-82-1 tetramethyl-2,2,3,3 butane 
• 590-66-9 1,1-dimethylcyclohexane 
• 590-67-0 1-Methylcyclohexanol 
• 20440-81-7 1-tert-butyladamantane 
• 4132-48-3 1-methoxy-4-(1-methylethyl)benzene 
• 75431-27-5 (4R,7R,7aR)-5,5-Dimethyl-octahydro-4,7-methano-indene 

Relevant academic research and scientific papers

Synthetic Utility of Organometallic Reagents Derived from. Group IV Metal Tetrachlorides and CH3Li. A Direct Synthesis of 2-(2-Keto-1-alkylidene)tetrahydropyrroles from 4-Alkynylamines and Acyl Cyanides

The non-Cp-bearing titanium alkyls (CH3)2TiCl2 · L2(1a) and (CH3)2Ti(OTFE)Cl · L2 (1b) and their Zr(IV) analogues have been shown to mediate efficient aminoalkyne cyclizations to provide azatitanium intermediates that undergo facial C-acylation in the presence of acyl cyanides.

Catalytic asymmetric formal total synthesis of (+)-dichroanone and (+)-taiwaniaquinone H

Catalytic asymmetric formal total synthesis of (+)-dichroanone and (+)-taiwaniaquinone H has been achieved. Key step involved construction of all-carbon quaternary carbon by palladium-catalyzed conjugate addition of arylboronic acid to 3-methyl cyclohexenone. Furthermore, a new approach to build [6-5-6] tricyclic backbone via formyl introduction and subsequent aldol-type condensation was also explored.

Titanium methyl tamed on silica: Synthesis of a well-defined pre-catalyst for hydrogenolysis of: N-alkane

Alkylation of Ti(CH3)2Cl21 by MeLi gives the homoleptic Ti(CH3)42 for the first time in the absence of any coordinating solvent. The reaction of 2 with silica pretreated at 700 °C (SiO2-700) gives two inequivalent silica-supported Ti-methyl species 3. Complex 3 was characterized by IR, microanalysis (ICP-OES, CHNS, and gas quantification), and advanced solid-state NMR spectroscopy (1H, 13C, DQ, TQ, and HETCOR). The catalytic activity of the pre-catalyst 3 is investigated in low-temperature hydrogenolysis of propane and n-butane with TONs of 419 and 578, respectively. This journal is

Titanium Catalysts with Linked Indenyl-Amido Ligands for Hydroamination and Hydroaminoalkylation Reactions

Titanium complexes containing a bridging indenylethylamido ligand have been synthesized and used as catalysts for hydroamination and hydroaminoalkylation reactions. All dichloro titanium complexes (η5:η1-Ind-C2H4-NR)TiCl2 (R = i-Pr (2a), t-Bu (2b), Cy (2c), Ph (2d)), which were prepared by reacting TiCl4(Et2O)2 with Li2[Ind-C2H4-NR], were fully characterized by single-crystal X-ray analysis. Reaction of 2a-c with methyllithium gave the thermally sensitive corresponding dimethyl titanium complexes [η5:η1-Ind-C2H4-N(alkyl)]TiMe2 (alkyl = i-Pr (3a), t-Bu (3b), Cy (3c)), while the N-aryl-substituted dimethyl titanium complexes [η5:η1-Ind-C2H4-N(aryl)]TiMe2 (aryl = Ph (3d), p-MeOC6H4 (3e)) were directly prepared by reacting Li2[Ind-C2H4-N(aryl)] with in situ generated Cl2TiMe2. In the case of complex 3d, the molecular structure could be determined by single-crystal X-ray analysis. All dimethyl titanium complexes (η5:η1-Ind-C2H4-NR)TiMe2 (R = i-Pr (3a), t-Bu (3b), Cy (3c), Ph (3d), p-MeOC6H4 (3e)) were finally used as precatalysts for the intermolecular hydroaminoalkylation of 1-octene (4), the intramolecular hydroamination and hydroaminoalkylation reactions of aminoalkenes, and the intermolecular hydroamination of 1-phenylpropyne (12). These experiments showed that the N substituent of the indenylethylamido ligand strongly influences the activity of the catalysts in the individual reactions.

Inhibition of hypoxia-induced gene transcription by substituted pyrazolyl oxadiazoles: Initial lead generation and structure-activity relationships

The transcription factors hypoxia-inducible factor-1 and -2 (HIF-1 and HIF-2) orchestrate a multitude of processes that allow tumor cells to survive under conditions of low oxygen and nutrients, and that lead to resistance to some apoptotic pathways and facilitate invasion and metastasis. Therefore, inhibition of transactivation by HIF has become an attractive target in cancer research. Herein we present the results of a cell-based screening approach that led to the discovery of substituted 1H-pyrazole-3-carboxamides. Chemical optimization of the hit class with respect to potency and metabolic stability is described; it resulted in novel 5-(1H-pyrazol-3-yl)-1,2,4-oxadiazoles that inhibit the hypoxia-induced accumulation of HIF-1α and HIF-2α. The HIF inhibitory potency in the screening cell system was improved from IC 50 190 to 0.7 nM, and significant parts of the SAR are disclosed. For a key compound, the ability to suppress the hypoxia-induced expression of HIF target genes was studied in A549 human lung adenocarcinoma cells. The same compound shows a favorable pharmacokinetic profile in rats after i.v. and p.o. administration. Suppressing HIF target genes: Substituted 5-(1H-pyrazol-3-yl)-1, 2,4-oxadiazoles are presented as a novel chemotype to specifically inhibit the hypoxia-induced transcription of target genes of the transcription factor hypoxia-inducible factor (HIF). The new chemotype was derived from 1H-pyrazole-3-carboxamides that had been discovered from a cell-based screen. We present the optimization of the potency and metabolic stability of the initial screening hit. Copyright

Substituted heterocyclylbenzylpyrazoles and use thereof

The present application relates to novel substituted 1-[3-(heterocyclyl)benzyl]-1H-pyrazole derivatives, to processes for preparation thereof, to use thereof for treatment and/or prevention of diseases and to use thereof for production of medicaments for treatment and/or prevention of diseases, more particularly for treatment and/or prevention of hyperproliferative and angiogenic diseases and those diseases which arise from metabolic adaptation to hypoxic states. Such treatments can be effected in the form of monotherapy or else in combination with other medicaments or further therapeutic measures.

HETEROAROMATIC COMPOUNDS FOR USE AS HIF INHIBITORS

The present application relates to novel substituted aryl compounds, processes for their preparation, their use for treatment and/or prevention of diseases and their use for the preparation of medicaments for treatment and/or prevention of diseases, in particular for treatment and/or prevention of hyperproliferative and angiogenic diseases and those diseases which arise from metabolic adaptation to hypoxic states. Such treatments can be carried out as monotherapy or also in combination with other medicaments or further therapeutic measures.

Formation of CH3TiX, CH2=TiHX, and (CH 3)2TiX2 by reaction of methyl chloride and bromide with laser-ablated titanium atoms: Photoreversible α-hydrogen migration

The simple methylidene (CH2=TiHX) and Grignard-type (CH 3TiX) complexes are produced by reaction of methyl chloride and bromide with laser-ablated Ti atoms and isolated in a solid Ar matrix, and they form a persistent photoreversible system via α-hydrogen migration between the carbon and titanium atoms. The Grignard-type product is transformed to the methylidene complex upon UV (240 nm 530 nm) irradiation. More stable dimethyl dihalide complexes [(CH3)2TiX2] are also identified, whose relative concentration increases upon annealing and at high methyl halide concentration. The reaction products are identified with three different groups of absorptions on the basis of the behaviors upon broadband photolysis and annealing, and the vibrational characteristics are in a good agreement with DFT computation results.

Molecular Structure of Dimethyldichlorotitanium(IV) by Gas-Phase Electron Diffraction, IR and NMR Spectroscopies, and Density Functional Theory Calculations. Unexpected Distortion from Tetrahedral Coordination Geometry

The molecular structure of (CH3)2TiCl2 has been determined by gas-phase electron diffraction. The bond distances are Ti-C = 205.8(4) pm and Ti-Cl = 219.6(3) pm, and the valence angles are Cl-Ti-Cl = 117.3(3)°, Cl-Ti-C = 108.9(2)°, and C-Ti-C = 102.8(9)°. The larger valence angles at Ti are thus those spanned by the more electronegative substituents. This is opposite to the trend observed in the main group analogues (CH3)2-ECl2, E = Si, Ge, or Sn. Density functional theory (DFT) calculations with a triple-ζ basis yield an optimal structure in good agreement with experiment. There is nothing in the gas-phase electron diffraction structure, DFT calculations, gas-phase IR spectra, or the NMR spectra of (CH2D)2TiCl2 hinting at unusual methyl group geometries or agostic Ti...H-C interactions.

Direct Geminal Dimethylation of Ketones and Exhaustive Methylation of Carboxylic Acid Chlorides Using Dichlorodimethyltitanium

The reaction of ketones with an excess of (CH3)2TiCl2 (6) leads to the replacement of the carbonyl oxygen atom by two methyl groups.This mild method of direct geminal dimethylation involves Grignard-type addition followed by formation of tertiary carbocations which are captured by methyltitanium species.Additional functional groups such as primary alkyl chlorides, thioethers, aromatics, ethers and esters are tolerated, but not thioketals.The procedure has been applied to the synthesis of (+/-)-cuparene (44).Similarly, carboxylic acid chlorides are converted to tert-butyl derivatives.