90609-94-2

Upstream product

• 77-78-1 dimethyl sulfate 
• 22013-33-8 6-amino-3,4-benzodioxane 
• 950824-98-3 (2,3-dihydro-benzo[1,4]dioxin-6-yl)-methyl-carbamic acid benzyl ester 
• 67-56-1 methanol 
• 16498-20-7 6-nitro-2,3-dihydrobenzo[b][1,4]dioxine 
• 50-00-0 formaldehyd 

Relevant academic research and scientific papers

Electronically tuneable orthometalated RuII–NHC complexes as efficient catalysts for C–C and C–N bond formations via borrowing hydrogen strategy

The catalytic activities of a series of simple and electronically tuneable cyclometalated RuII–NHC complexes (2a–d) were explored in various C–C/N bond formations following the borrowing hydrogen process. Slight modifications in the ligand backbone were noted to tune the activities of these complexes. Among them, the complex 2d featuring a 1,2,4-triazolylidene donor with a 4-NO2–phenyl substituent displayed the highest activity for the coupling of diverse secondary and primary alcohols with a low catalyst loading of 0.01 mol% and a sub-stoichiometric amount of inexpensive KOH base. The efficacy of this simple system was further showcased in the challenging one-pot unsymmetrical double alkylation of secondary alcohols using different primary alcohols. Moreover, the complex 2d also effectively catalyses the selective mono-N-methylation of various aromatic and aliphatic primary amines using methanol to deliver a range of N-methyl amines. Mechanistically, the β-alkylation reaction follows a borrowing hydrogen pathway which was established by the deuterium labelling experiment in combination with various control experiments. Intriguingly, in situ1H NMR and ESI-MS analyses evidently suggested the involvement of a Ru–H species in the catalytic cycle and further, the kinetic studies revealed a first order dependence of the reaction rate on the catalyst as well as the alcohol concentrations.

Simple RuCl3-catalyzed N-Methylation of Amines and Transfer Hydrogenation of Nitroarenes using Methanol

Methanol is a potential hydrogen source and C1 synthon, which finds interesting applications in both chemical synthesis and energy technologies. The effective utilization of this simple alcohol in organic synthesis is of central importance and attracts scientific interest. Herein, we report a clean and cost-competitive method with the use of methanol as both C1 synthon and H2 source for selective N-methylation of amines by employing relatively cheap RuCl3.xH2O as a ligand-free catalyst. This readily available catalyst tolerates various amines comprising electron-deficient and electron-donating groups and allows them to transform into corresponding N-methylated products in moderate to excellent yields. In addition, few marketed pharmaceutical agents (e. g., venlafaxine and imipramine) were also successfully synthesized via late-stage functionalization from readily available feedstock chemicals, highlighting synthetic value of this advanced N-methylation reaction. Using this platform, we also attempted tandem reactions with selected nitroarenes to convert them into corresponding N-methylated amines using MeOH under H2-free conditions including transfer hydrogenation of nitroarenes-to-anilines and prepared drug molecules (e. g., benzocaine and butamben) as well as key pharmaceutical intermediates. We further enable one-shot selective and green syntheses of 1-methylbenzimidazole using ortho-phenylenediamine (OPDA) and methanol as coupling partners.

Identification of 2-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)amino)-N-phenylpropanamides as a novel class of potent DprE1 inhibitors

The identification of a novel series of DprE1 inhibitors based on a 2-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)amino)-N-phenylpropanamide scaffold is described herein. SAR exploration around the HTS hit 1 led to the identification of multiple analogues with potent DprE1 inhibition and good whole-cell antimycobacterial activity.

Room temperature N-heterocyclic carbene manganese catalyzed selective N-alkylation of anilines with alcohols

The first example of room temperature non-noble metal homogeneous system catalyzed selective N-alkylation of anilines with alcohols by a bis-NHC manganese complex is presented. This system was applied to a large range of alcohols and anilines, including biologically relevant motifs and challenging methanol. Experimental and computational studies suggest an outer-sphere mechanism for this NHC-Mn system.

N-Methylation of amines and nitroarenes with methanol using heterogeneous platinum catalysts

We report herein the selective N-methylation of amines and nitroarenes with methanol under basic conditions using carbon-supported Pt nanoparticles (Pt/C) as a heterogeneous catalyst. This method is widely applicable to four types of N-methylation reactions: (1) N,N-dimethylation of aliphatic amines under N2, (2) N-monomethylation of aliphatic amines under 40 bar H2, (3) N-monomethylation of aromatic amines under N2, and (4) tandem synthesis of N-methyl anilines from nitroarenes and methanol under 2 bar H2. All these reactions under the same catalytic system showed high yields of the corresponding methylamines for a wide range of substrates, high turnover number (TON), and good catalyst reusability. Mechanistic studies suggested that the reaction proceeded via a borrowing hydrogen methodology. Kinetic results combined with density functional theory (DFT) calculations revealed that the high performance of Pt/C was ascribed to the moderate metal–hydrogen bond strength of Pt.

Commercial Pd/C-Catalyzed N-Methylation of Nitroarenes and Amines Using Methanol as Both C1 and H2 Source

Herein, we report commercially available carbon-supported-palladium (Pd/C)-catalyzed N-methylation of nitroarenes and amines using MeOH as both a C1 and a H2 source. This transformation proceeds with high atom-economy and in an environmentally friendly way via borrowing hydrogen mechanism. A total of >30 structurally diverse N-methylamines, including bioactive compounds, were selectively synthesized with isolated yields of up to 95%. Furthermore, selective N-methylation and deuteration of nimesulide, a nonsteroidal anti-inflammatory drug, were realized through the late-stage functionalization.

PYRAZOLE DERIVATIVES FOR THE TREATMENT OF CYSTIC FIBROSIS

The present invention relates to compounds of Formula (I) or pharmaceutically acceptable salts or solvates thereof. It further discloses a pharmaceutical composition comprising the compounds of Formula (I) and their uses, in particular to modulate CFTR protein or ABC protein activities.

Effects of the tumor-vasculature-disrupting agent verubulin and two heteroaryl analogues on cancer cells, endothelial cells, and blood vessels

Two analogues of the discontinued tumor vascular-disrupting agent verubulin (Azixa, MPC-6827, 1) featuring benzo-1,4-dioxan-6-yl (compound 5 a) and N-methylindol-5-yl (compound 10) residues instead of the para-anisyl group on the 4-(methylamino)-2-methylquinazoline pharmacophore, were prepared and found to exceed the antitumor efficacy of the lead compound. They were antiproliferative with single-digit nanomolar IC50 values against a panel of nine tumor cell lines, while not affecting nonmalignant fibroblasts. Indole 10 surpassed verubulin in seven tumor cell lines including colon, breast, ovarian, and germ cell cancer cell lines. In line with docking studies indicating that compound 10 may bind the colchicine binding site of tubulin more tightly (Ebind=-9.8 kcal mol-1) than verubulin (E bind=-8.3 kcal mol-1), 10 suppressed the formation of vessel-like tubes in endothelial cells and destroyed the blood vessels in the chorioallantoic membrane of fertilized chicken eggs at nanomolar concentrations. When applied to nude mice bearing a highly vascularized 1411HP germ cell xenograft tumor, compound 10 displayed pronounced vascular-disrupting effects that led to hemorrhages and extensive central necrosis in the tumor. Variations on a promising theme: Tumor blood vessels are a good therapeutic target because they are fundamentally different from normal vasculature. This study shows that vascular-disrupting agents derived from verubulin have enhanced selectivity for cancer cells and lower general in vivo toxicity, yet they retain the strong antivascular activity of the lead compound.

CYCLOHEXYL OR PIPERIDINYL CARBOXAMIDE ANTIBIOTIC DERIVATIVES

The invention relates to antibiotic cyclohexyl or piperidinyl carboximide derivatives of formula (I) wherein R1 represents hydrogen, halogen, (C1-C4)alkyl, (C1-C4)alkoxy, cyano or COOR2, R2 being (C1-C4)alkyl;one or two of U, V, W and X represent(s) N and the remaining represent each CH, or, in the case of X, may also represent CRX, RX being a halogen atom;either B represents N and A represents CH2CH2 or CH(OR3)CH2, or B represents CH or C(OR4) and A represents OCH2, CH2CH(OR5), CH(OR6)CH2, CH(OR7)CH(OR8), CH═CH or CH2CH2;each of R3, R4, R5, R6, R7, and R8 represents independently hydrogen, SO3H, PO3H2, CH2OPO3H2 or COR9, R9 being either CH2CH2COOH or such that R9—COOH is naturally occurring amino acid or dimethylaminoglycine;and to salts of such compounds of formula (I).

CYCLOHEXYL OR PIPERIDINYL CARBOXAMIDE ANTIBIOTIC DERIVATIVES

The invention relates to antibiotic cyclohexyl or piperidinyl carboxamide derivatives of formula (I) wherein R1 represents hydrogen, halogen, (C1-C4)alkyl, (C1-C4)alkoxy, cyano or COOR2, R2 being (C1-C4)alkyl; one or two of U, V, W and X represent(s) N and the remaining represent each CH, or, in the case of X, may also represent CRx, Rx being a halogen atom; either B represents N and A represents CH2CH2 or CH(OR3)CH2, or B represents CH or C(OR4) and A represents OCH2, CH2CH(OR5), CH(OR6)CH2, CH(OR7)CH(OR8), CH=CH or CH2CH2; each of R3, R4, R5, R6, R7 and R8 represents independently hydrogen, SO3H, PO3H2, CH2OPO3H2 or COR9, R9 being either CH2CH2COOH or such that R9-COOH is a naturally occurring amino acid or dimethylaminoglycine; and to salts of such compounds of formula (I).