287930-73-8Relevant articles and documents
Preparation methods of aprepitant impurity
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Paragraph 0118-0119; 0127-0128, (2020/07/13)
The invention discloses preparation methods of an aprepitant impurity, which comprise isomer impurity synthesis method of six aprepitant key intermediates (2R, 3S)-2-[(1R)-1-[3, 5-bis (trifluoromethyl)-phenyl] ethoxy]-3-(4-fluorophenyl) morpholine, respectively, synthesis of four diastereomer impurities, synthesis of one enantiomer impurity and synthesis of one by-product impurity. The methods have the beneficial effects that the five synthesis methods are simple and feasible, the raw materials are easy to obtain, the conditions are mild, the cost is low, the production is facilitated, and meanwhile, the isomer impurities of the synthesized aprepitant key intermediate provide a new intermediate raw material for the preparation of aprepitant.
A kind of preparation method of dimethyl luck Sha Pitan cyclophosphadenosine
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Paragraph 0031-0033, (2017/04/07)
The invention relates to a method for preparing fosaprepitant. The fosaprepitant is shown as a formula (I). The method comprises steps 1, 2, 3 and 4, finally, a compound shown as the formula (I) is obtained through hydrogenation reduction; in the step 1, a compound in a formula (II) reacts with a Grignard reagent to generate a compound shown as a formula (III) in the presence of palladium carbon and ammonium formate. The method for preparing is simple in production step, has high reaction yield and less side products, is easy in control of the reaction conditions and is suitable for medical industrial production.
A process for the preparation of intermediates luck Sha Pitan
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Paragraph 0020; 0021; 0022, (2019/02/02)
The invention relates to a method for preparing a fosaprepitant intermediate which is a compound shown in a formula (I). The method includes the steps of reacting a compound in a formula (II) and glyoxylic acid to generate a compound in a formula (III), reacting the compound in the formula (III) and (R)-1-(3,5-bi(trifluoromethyl) phenyl) ethanol, and then separating and purifying. According to the method, preparation steps are simple, the reaction yield is high, and the fosaprepitant intermediate is suitable for large-scale production of medical industry.
Syntheses of morpholine-2,3-diones and 2-hydroxymorpholin-3-ones: Intermediates in the synthesis of aprepitant
Nelson, Todd D.,Rosen, Jonathan D.,Brands, Karel M.J.,Craig, Bridgette,Huffman, Mark A.,McNamara, James M.
, p. 8917 - 8920 (2007/10/03)
The preparation of morpholine-2,3-diones and 2-hydroxymorpholin-3-ones from N-substituted β-amino alcohols is reported. These were useful intermediates in the synthesis and development of aprepitant.
Efficient synthesis of NK1 receptor antagonist aprepitant using a crystallization-induced diastereoselective transformation
Brands, Karel M. J.,Payack, Joseph F.,Rosen, Jonathan D.,Nelson, Todd D.,Candelario, Alexander,Huffman, Mark A.,Zhao, Matthew M.,Li, Jing,Craig, Bridgette,Song, Zhiguo J.,Tschaen, David M.,Hansen, Karl,Devine, Paul N.,Pye, Philip J.,Rossen, Kai,Dormer, Peter G.,Reamer, Robert A.,Welch, Christopher J.,Mathre, David J.,Tsou, Nancy N.,McNamara, James M.,Reider, Paul J.
, p. 2129 - 2135 (2007/10/03)
An efficient stereoselective synthesis of the orally active NK1 receptor antagonist Aprepitant is described. A direct condensation of N-benzyl ethanolamine with glyoxylic acid yielded a 2-hydroxy-1,4-oxazin-3-one which was activated as the corresponding trifluoroacetate. A Lewis acid mediated coupling with enantiopure (R)-1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-ol afforded a 1:1 mixture of acetal diastereomers which was converted into a single isomer via a novel crystallization-induced asymmetric transformation. The resulting 1,4-oxazin-3-one was converted via a unique and highly stereoselective one-pot process to the desired α-(fluorophenyl)morpholine derivative. Interesting and unexpected [1,2]-Wittig and [1,3]-sigmatropic rearrangements were identified during the optimization of these key steps. In the final step, a triazolinone side chain was appended to the morpholine core. The targeted clinical candidate was thus obtained in 55% overall yield over the longest linear sequence.
