佐米曲坦置于水,Sodium Carbonate,盐酸,Sodium Hydroxide体系中,用 水 用作溶剂,化学反应 5.5H,以77%的收率获得佐米曲普坦 参考文献:Process For Preparing Optically Pure Zolmitriptan 标题:Process For Preparing Optically Pure Zolmitriptan 摘要:一种制备唑米替普坦的方法,通过中间体乙基-3-[2-(1,3-二氧杂环庚-2,3-二酮基)乙基]-5-[(4S)-2-氧代-1,3-噁唑-4-基甲基]-1H-2-吲哚羧酸酯进行.
专利号:US-8822702-B2 优先权日:2002-12-20 标 题 :Synthesis of amines and intermediates for the synthesis thereof 发明人:BERENS ULRICH; DOSENBACH OLIVER; SPRENGER DANIEL 权利人:BERENS ULRICH; DOSENBACH OLIVER; SPRENGER DANIEL; BASF SE 摘要:The invention relates in a first embodiment to a method for the manufacture of esters of the formula I, n nor especially of amides of the formula II,n n nwherein the symbols have the meanings given in the specification, as well as other intermediates and compounds useful in the synthesis of tryptamines and other substances mentioned in the title. The synthesis methods and intermediates are useful in the synthesis of pharmaceuticals.
专利号:US-2025188502-A1 优先权日:2022-03-10 标 题 :Biocatalyst and method for the synthesis of ubrogepant intermediates 发明人:CHEN HAIBIN; HU HU; CAI BAOQIN; XU JUNPENG; LIU SITONG; JIN LUPING; WU XINWEI; CUI QINYAN; ZHANG CHENGXIAO; ZHU KAILONG 权利人:ENZYMASTER NINGBO BIO ENG CO LTD 摘要:This application provides engineered transaminase polypeptides for the synthesis of Ubrogepant intermediates with high stereoselectivity, high catalytic activity and good stability. This application also provides a reaction process for the asymmetric synthesis of Ubrogepant intermediates using the transaminase polypeptide.
专利号:US-7786156-B2 优先权日:2004-01-28 标 题 :Synthesis methods and intermediates for the manufacture of Rizatriptan 发明人:MARTIN PIERRE; BERENS ULRICH; BOUDIER ANDREAS; DOSENBACH OLIVER 权利人:RATIOPHARM GMBH 摘要:The invention relates to a process for the manufacture of an 1,2,4-triazol-1-yl compound of the formula [A], n nor a salt thereof, wherein each of R3 and R4 is hydrogen or lower alkyl, said process comprising reacting a hydrazine compound of the formula [B]n n nwherein R is hydrogen or acyl, R2 is hydrogen or a protecting group, are hydrogen or lower alkyl, and R6 is hydrogen or COOR7, or a salt thereof, with a 1,2,4-triazolyl forming reagent.n n In addition, novel intermediates for the synthesis of the anti-migraine agent Rizatriptan and methods for their synthesis are presented.
专利号:US-7563904-B2 优先权日:2002-08-07 标题:Synthesis intermediates useful for preparing zolmitriptan 发明人:DALMASES BARJOAN PERE; ARMENGOL ASPARO MONTSERRAT 权利人:INKE SA 摘要:In particular, this invention relates to the synthesis intermediates (IV), (V), (VI) and (VIII) useful for preparing zolmitriptanzohnitriptan or a pharmaceutically acceptable salt thereof, which includes a) Ppreparation of the diazonium salt of the aniline hydrochloride (II); followed by reduction and acidification to give hydrazine (III); b) In situ Reaction of the hydrazine hydrochloride (III) with α-keto-δ-valerolactone, to give the hydrazone (IV); c) Fischer indole synthesis of the hydrazone (IV), to give the pyranoindolone of formula (V); d) Ttransesterification of the pyranoindolone (V) to provide the compound (VI), in which R means a straight or branched C1-C4 alkyl; e) Conversion of the hydroxyl group of the compound (VI) into dimethylamino to give the indolecarboxylate (VII), in which R means a straight or branched C1-C4 alkyl; f) Ssaponification of the 2-carboalkoxy group of the compound (VII), to provide indolecarboxylic acid (VIII); g) Ddecarboxylation of the indolecarboxylic acid (VIII), to provide zolmitriptan and, eventually, to provide a pharmaceutically acceptable salt thereof.
专利号:WO-03101931-A3 优先权日:2002-05-31 标题:Preparation of 4-(n, n-disubstitutedamino) butyraldehyde acetals 发明人:PULLA REDDY MUDDASANI; VENKAIAH CHOWDARY NANNAPANENI 权利人:NATCO PHARMA LTD; PULLA REDDY MUDDASANI; VENKAIAH CHOWDARY NANNAPANENI 摘要:The invention disclosed in this application relates to an improved process for the preparation of compounds of formula (I): R1R2NCH2CH2CH2CH(OR3)2; wherein, R1 = R2 = C1-C16 alkyl; C3-C7 cycloalkyl; R1 = C1-C16 alkyl; R2 = C3-C7 cycloalkyl; NR1R2 = pyrrolidino, piperidino, morpholino, thiomorpholino, R1 = C1-C6 alkyl; R2 = ArCH2; Ar =4-R4-C6H4-, R4 = MeO, EtO, Me, Et, NMe2, NEt2, SMe, SEt, etc; R3=C1-C6 alkyl; C3-C7 cycloalkyl which comprises: (i) Reacting 3-(N, N-disubstitutedamino)propyl halide of formula (XXI): R1R2NCH2CH2CH2X; wherein, R1, R2 = as defined above, X = C1 or Br, with magnesium in the presence of a solvent to get the Grrgnard reagent 3-(N, N-disubstitutedamino)-propylmagnesium halide; (ii) Reacting the resulting 3-(N, N-disubstitutedamino) propylmagnesium halide (Grignard reagent) with the trisubstituted orthoformate of formula (XVII): HC(OR5)(OR3)2; wherein, R3 and R5 is same or different and represent C1 to C6 alkyl, C3 to C7 cycloalkyl OR R3 is as defined above and R5 represents phenyl radical; (iii) Filtering off the resultant reaction mixture and distilling the filtrate to isolate the compound of the formula (I). These substituted butyraldehyde derivatives of the formula (I) are very important building blocks for the synthesis of various tryptamine derivatives. In particular 4-(N, N-dimethylamino)butyraldehyde dimethyl or diethyl acetals are crucial intermediates for the synthesis of commercially available anti-migraine drugs, like sumatriptan, zolmitriptan, and rizatriptan.
专利号:US-6303791-B1 优先权日:1995-08-07 标题 :One pot synthesis of 2-oxazolidinone derivatives 发明人:PATEL RAJNIKANT 权利人:ZENECA LTD 摘要:The invention provides an improved process for preparing compounds of formula (I
1: Bird S, Derry S, Moore RA. Zolmitriptan for acute migraine attacks in adults. Cochrane Database Syst Rev. 2014 May 21;5:CD008616. doi: 10.1002/14651858.CD008616.pub2. Review. doi: 10.1111/head.12181. Review. Review. Review. 5: Goadsby PJ, Yates R. Zolmitriptan intranasal: a review of the pharmacokinetics and clinical efficacy. Headache. 2006 Jan;46(1):138-49. Review. Review. Review. Review. Review. Review. Review. Review. French. Review. Review. Spanish. Review. Spanish. Review. Spanish. Review. Review. Cephalalgia. 1997 Oct;17 Suppl 18:4-14. Review. Review.
合成参考文献
参考文献:10.1016/j.ajem.2009.05.021 摘要:Acikel S, Dogan M, Sari M, Kilic H, Akdemir R. Prinzmetal-variant angina in a patient using zolmitriptan and citalopram. The American Journal of Emergency Medicine. 2010 Feb;28(2):257.e3–6. doi: 10.1016/j.ajem.2009.05.021. 参考文献:10.2165/11590370-000000000-00000 摘要:Källén B, Nilsson E, Otterblad Olausson P. Delivery outcome after maternal use of drugs for migraine: a register study in Sweden. Drug Saf. 2011 Aug 01;34(8):691–703. doi: 10.2165/11590370-000000000-00000.