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【结 构 式】

【分子编号】51944

【品名】N-(trichloromethyl)-3-butenamide

【CA登记号】

【 分 子 式 】C5H6Cl3NO

【 分 子 量 】202.46688

【元素组成】C 29.66% H 2.99% Cl 52.53% N 6.92% O 7.9%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XVIII)

Alternatively, compound (XV) can also be obtained as follows: Reduction of (S)-maleate (XVI) with BMS-NaBH4 in THF, followed by O-protection with TBDPS-Cl and imidazole, yields alcohol (XVII), which is first allylated with allyl trichloroacetimidate (XVIII) catalyzed by triflic acid in cyclohexanes and then reduced with DIBAL in THF to provide compound (XIX). Ozonolysis of (XIX) in MeOH, followed by reductive quench with NaBH4, gives diol (XX), which is then converted into bismesylate (XXI) by treatment with MsCl and Et3N in ether. Compound (XXI) is subjected to a double Finkelstein reaction with NaI in acetone in the presence of NaHCO3 to yield bisiodide (XXII) (1), which is then coupled with 3-bis(1H-indol-3-yl)-N-methylmaleimide (XI) by means of Cs2CO3 in DMF to give intermediate (XV).

1 Engel, G.L.; Farid, N.A.; Faul, M.M.; Jirousek, M.R.; Richardson, L.A.; Winneroski, L.L. Jr. (Eli Lilly and Company); Protein kinase C inhibitor. EP 0776895; JP 1999500149; US 5710145; WO 9718809 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XI) 41012 3,4-di(1H-indol-3-yl)-1-methyl-1H-pyrrole-2,5-dione 113963-68-1 C21H15N3O2 详情 详情
(XV) 41016 (18S)-4-methyl-18-[(trityloxy)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1(7,14).0(2,6).0(8,13).0(22,27)]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione C46H39N3O4 详情 详情
(XVI) 11806 dimethyl (2S)-2-hydroxybutanedioate 617-55-0 C6H10O5 详情 详情
(XVII) 41019 methyl (3S)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-hydroxybutanoate C21H28O4Si 详情 详情
(XVIII) 51944 N-(trichloromethyl)-3-butenamide C5H6Cl3NO 详情 详情
(XIX) 41021 (3S)-3-(allyloxy)-4-[[tert-butyl(diphenyl)silyl]oxy]-1-butanol C23H32O3Si 详情 详情
(XX) 41023 (3S)-4-[[tert-butyl(diphenyl)silyl]oxy]-3-(2-hydroxyethoxy)-1-butanol C22H32O4Si 详情 详情
(XXI) 51948 (7S)-2,11,11-trimethyl-7-(2-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]ethyl)-2-methylene-10,10-diphenyl-3,6,9-trioxa-2lambda(6)-thia-10-sila-1-dodecene; tert-butyl(diphenyl)silyl (2S)-4-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-2-(2-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]ethoxy)butyl ether C28H44O4S2Si 详情 详情
(XXII) 41025 tert-butyl(diphenyl)silyl (2S)-4-iodo-2-(2-iodoethoxy)butyl ether; tert-butyl[[(2S)-4-iodo-2-(2-iodoethoxy)butyl]oxy]diphenylsilane C22H30I2O2Si 详情 详情
Extended Information