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    • 6. 发明申请
    • HYDROFORMYLATION PROCESS FOR PHARMACEUTICAL INTERMEDIATE
    • 药物中间体的水解过程
    • WO2005110986A1
    • 2005-11-24
    • PCT/US2005/014349
    • 2005-04-26
    • DOW GLOBAL TECHNOLOGIES INC.DAUGS, Edward, D.PENG, Wei-JunRAND, Cynthia, L.
    • DAUGS, Edward, D.PENG, Wei-JunRAND, Cynthia, L.
    • C07D209/48
    • C07D401/06C07D209/48C07D471/04
    • The invention relates to an improved process for the preparation of an advanced synthetic intermediate of ACE inhibitors. In one aspect, the present invention is based on a novel process for the preparation of an aldehyde of formula (I), wherein (N) PrG is a protected amino group, R is an alkyl or aralkyl group and X 1-4 are each independently H or a non-reacting substituent, which comprises hydroformylation of an α-olefin of formula (II), by reaction with syngas (CO/H 2 ) in the presence of, as catalyst, a group VIII transition metal complex of a phosphorus-containing ligand. Aldehyde (I), the product of linear hydroformylation, is formed in preference to aldehyde (III). In another aspect of the invention, α-olefin (II) is a novel composition. The process to convert (II) to (I) enables an efficient manufacturing route to MDL 28,726 and analogues.
    • 本发明涉及用于制备ACE抑制剂的高级合成中间体的改进方法。 一方面,本发明是基于制备式(I)的醛的新方法,其中(N)PrG是被保护的氨基,R是烷基或芳烷基,X <1-4> 各自独立地是H或非反应性取代基,其包括式(II)的α-烯烃的羰基化,通过在作为催化剂的催化剂存在下与合成气(CO / H 2)反应的第VIII族过渡金属络合物 含磷配体。 醛(I)是线性加氢甲酰化的产物,优选醛(III)。 在本发明的另一方面,α-烯烃(II)是一种新的组合物。 将(II)转化为(I)的过程能够实现MDL 28,726和类似物的有效制造路线。
    • 7. 发明申请
    • PROCESS FOR MAKING AMINO ACIDS
    • 制备氨基酸的方法
    • WO2007084545A1
    • 2007-07-26
    • PCT/US2007/001207
    • 2007-01-17
    • DOW GLOBAL TECHNOLOGIES INC.LLOYD, Michael, C.DAUGS, Edward, D.RAND, Cynthia, L.PENG, Wei-jun
    • LLOYD, Michael, C.DAUGS, Edward, D.RAND, Cynthia, L.PENG, Wei-jun
    • C07C227/32C07D317/30C12P41/00
    • C07C227/32C07D317/30C12P13/04C12P41/006
    • A process for making an amino acid by the steps of: (a) contacting a compound of formula I with a hydroformylation catalyst and synthesis gas to produce a mixture of aldehyde compounds comprising the formulas IIa, IIb and IIc; (b) reacting the mixture of aldehyde compounds from step (a) to produce a mixture of derivative compounds comprising a masked amino acid derivative which may be selected from the group consisting of amino nitrile, N-acyl amino acid, amino amide, hydantoin and amino ester; (c) contacting the mixture of derivative compounds from step (b) with an enantioselective hydrolase enzyme in the presence of water to produce an L-amino acid having the formula IV; (d) isolating the amino acid having the formula IV in substantially pure form, wherein in formulas I, IIa, IIb, IIc, IIIa, IIIb, IIIc and IV, R is H, alkyl or aryl and R 1 and R 2 are the same or different alkyl groups and wherein R 1 and R 2 may be fused.
    • 通过以下步骤制备氨基酸的方法:(a)使式I化合物与加氢甲酰化催化剂和合成气接触以产生包含式IIa,IIb和IIc的醛化合物的混合物; (b)使来自步骤(a)的醛化合物的混合物反应以产生包含可以选自氨基腈,N-酰基氨基酸,氨基酰胺,乙内酰脲和 氨基酯; (c)在水存在下将来自步骤(b)的衍生化合物的混合物与对映选择性水解酶接触以产生具有式IV的L-氨基酸; (d)以基本上纯的形式分离具有式IV的氨基酸,其中在式I,IIa,IIb,IIc,IIIa,IIIb,IIIc和IV中,R是H,烷基或芳基,R 1, SO 2和R 2是相同或不同的烷基,其中R 1和R 2和R 2可以是稠合的。