Search

A novel and concise synthesis towards DP2 receptor antagonist Fevipiprant (NVS-QAW039) was developed. The initial research route was suffering from lengthy access to the functionalized 7-aza-indole core followed by a low selective N(1)-alkylation with the benzyl side chain. These limitations were overcome by introducing the side chain early via reductive amination between the functionalized aldehyde and 2-amino-3-bromopyridine. Sonogashira coupling with prop-2-yn-1-ol introduces the 3 missing carbon atoms to build the 7-aza-indole core and sets the stage for the innovative Johnson-Claisen key step. Reaction of the advanced propargylic alcohol derivative with trimethyl orthoacetate leads to a reactive allene intermediate that spontaneously and selectively cyclizes to the 7-aza-indole QAW039-methly ester. QAW039 is isolated after ester saponification. Selectivity, yield, and ecological footprint of the new synthesis were significantly improved, and scalability was demonstrated.

3-Aminoimidazo[1,2-a]pyrazine is an important scaffold that is found in many drugs. This scaffold is rapidly accessible through a Groebke–Blackburn–Bienayme cyclisation starting from an aminopyrazine, an aldehyde and an isocyanide. A scale-up process of this multicomponent reaction has been achieved in high yield and with excellent purity. The scope and limitations of this process leading to various 3-aminoimidazo[1,2-a]pyrazines are disclosed.

The preparation of various 2-(7-azaindolyl)carboxylic esters by Pd-catalyzed coupling of Reformatsky reagents with TBDMS-protected 3-bromo-7-azaindoles leading to a wide range of arylated ester derivatives is reported. After removal of the protecting group, the corresponding free 2-(7-azaindolyl)carboxylic esters are obtained in satisfactory yields.

During the bending of tubes, specific geometric deviations from the desired shape geometry occur. These deformations comprise cross-sectional deformation, wall-thinning of the outer arc and wall-thickening of the inner arc. During the bending of parts with small bend factors, geometric deviations on the inner arc in form of waves and wrinkles may arise as other typical quality criteria. A quantitative evaluation of those deviations has yet to be defined. Currently, only an instruction for measuring the height of the wrinkles at the inner arc according to DIN EN 13480-4 is known. In this standard, only the two highest wrinkles and the valley in between are included. The characteristics of the wrinkle, especially the flank angle and the rise of deformation are disregarded, although they are responsible for the failure of the bent part. Tool damages can also occur. A development of an evaluation factor to assess deformations in the bow area for bent parts is presented in this paper. In addition, it will be possible to quantify geometric deviations in the bow area. By using the newly developed evaluation factor for geometrical deformations in the bow area, the determination of the quality of the bent part should become more reproducible.

The preparation of various 2-(7-azaindolyl)carboxylic esters by Pd-catalyzed coupling of Reformatsky reagents with TBDMS-protected 3-bromo-7-azaindoles leading to a wide range of arylated ester derivatives is reported. After removal of the protecting group, the corresponding free 2-(7-azaindolyl)carboxylic esters are obtained in satisfactory yields.

Sterically hindered molybdenum(III) amido complexes of the general type [Mo{(tBu)(Ar)N} 3 ] (1), upon treatment with CH 2 Cl 2 or other halogen donors, have been converted into highly effective catalysts for all kinds of alkyne metathesis reactions. Although the actual nature of the propagating species formed in situ is still elusive, halogen transfer to the Mo center of 1 plays a decisive role in the activation of such precatalysts. It was possible to isolate and characterize by X-ray crystallography some of the resulting molybdenum halide derivatives such as 15, 16 and 20 which themselves were shown to be catalytically active. Numerous applications illustrate the performance of the catalytic system 1/CH 2 Cl 2 which operates under mild conditions and tolerates an array of polar functional groups. The wide scope allows the method to be implemented into the total synthesis of sensitive and polyfunctional natural products. Most notable among them is a concise entry into the potent anticancer agents epothilone A (86) and C (88). The macrolide core of these targets is forged by ring closing alkyne metathesis (RCAM) of diyne 113, followed by Lindlar hydrogenation of cycloalkyne 114 thus formed. Since this strategy opens a stereoselective entry into (Z)-alkene 115, the approach is inherently more efficient than previous syntheses based on conventional RCM.

The suitably functionalized cyclopentanone derivatives 12, 13, 19, and 37 serve as common precursors for the synthesis of various prostaglandins, prostaglandin-1,15-lactones, and unnatural analogues thereof. All of them contain a 2-butynyl entity which is elaborated into the intact α side chain of the targets either via a sequence comprising ring closing alkyne metathesis/Lindlar reduction or via alkyne cross metathesis (ACM)/Lindlar reduction. These novel approaches are distinguished by (i) the ready accessibility of the required cyclopentenone substrates via a three-component coupling reaction, (ii) the inherent flexibility which allows one to make a series of analogues starting from these common platforms, (iii) a small number of steps, and (iv) an excellent overall yield. The key alkyne metathesis reactions are efficiently catalyzed either by the tungsten alkylidyne complex (t-BuO)3W⋮CCMe3 or, preferentially, by a catalyst formed in situ from Mo[N(t-Bu)(Ar)]3 and CH2Cl2, the reactivity of which can be...

The rotary draw bending process finds special use in the bending of parts with small bending radii. Due to the support of the forming zone during the bending process, semi-finished products with small wall thicknesses can be bent. One typical quality characteristic is the emergence of corrugations and wrinkles at the inside arc. Presently, the standard for the evaluation of wrinkles is insufficient. The wrinkles’ distribution along the longitudinal axis of the tube results in an average value [1]. An evaluation of the wrinkles is not carried out. Due to the lack of an adequate basis of assessment, coordination problems between customers and suppliers occur. They result from an imprecision caused by the lack of quantitative evaluability of the geometric deviations at the inside arc. The benchmark factor for the inside arc presented in this article is an approach to holistically evaluate the geometric deviations at the inside arc. The classification of geometric deviations is carried out according to the area of the geometric characteristics and the respective flank angles.

A ring closing alkyne metathesis reaction catalyzed by the molybdenum complex 26 followed by a Lindlar reduction of the resulting cycloalkyne product opens an efficient and stereoselective entry into epothilone A and C.

Europas Wirtschaft befindet sich durch die Globalisierung in einem sehr dynamischen Strukturwandel. Die Produktlebenszyklen werden zunehmend kurzer und der Druck auf die Unternehmen, in immer kurzeren Abstanden neue Produkte auf den Markt zu bringen, wird immer groser. Die damit einhergehende Dynamik stellt vor allem fur Neugrundungen eine grose Chance dar, da diese Unternehmen schneller technologische Neuerungen oder Innovation aufgreifen und im Unternehmen integrieren, oder ihr Geschaftskonzept auf diese neuen Chancen aufbauen konnen. „Universitare Ausgrundungen“ oder Spin Offs besitzen zudem durch die Nahe zur „Alma Mater“ in der Regel einen direkteren Zugang zu hoch qualifizierten Arbeitskraften, zur universitaren Infrastruktur, zur Forschungsleistung der Hochschulen, zu IPRs und wissenschaftlichen Netzwerken, die ihnen eine hohere Erfolgswahrscheinlichkeit sichern.