(2R,3S)-4-(4-azido-2-butynyl)-2-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-3-(4-fluorophenyl)morpholine; (2R,3S)-4-(4-azido-2-butynyl)-3-(4-fluorophenyl)morpholinyl (1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl ether -Drug Synthesis Database

【结构式】

【分子编号】53303

【品名】(2R,3S)-4-(4-azido-2-butynyl)-2-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-3-(4-fluorophenyl)morpholine; (2R,3S)-4-(4-azido-2-butynyl)-3-(4-fluorophenyl)morpholinyl (1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl ether

【CA登记号】n/a

【分子式】C₂₄H₂₁F₇N₄O₂

【分子量】530.4453224

【元素组成】C 54.34% H 3.99% F 25.07% N 10.56% O 6.03%

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：(XXXVII)

Alternatively, morpholine (XVIII) was alkylated with 1,4-dichloro-2-butyne (XXXV) in the presence of K2CO3 to afford the propargyl chloride (XXXVI). Displacement of the chloride of (XXXVI) with sodium azide in DMSO gave the propargylic azide (XXXVII). The title triazole was then produced via isomerization and cyclization of azide (XXXVII) upon heating with dimethylamine in a sealed tube.

参考文献中间体

合成目标

【1】 Harrison, T.; Owens, A.P.; Williams, B.J.; et al.; An orally active, water-soluble neurokinin-1 receptor antagonist suitable for both intravenous and oral clinical administration. J Med Chem 2001, 44, 24, 4296.
【2】 Baker, R.; Harrison, T.; Mcleod, A.M.; Owens, A.P.; Seward, E.M.; Swain, C.J.; Teall, M.R. (Merck Sharp & Dohme Ltd.); Substd. morpholine derivs. and their use as therapeutic agents. EP 0737192; EP 1099702; JP 1997507484; JP 2000219629; US 5612337; WO 9518124 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XVIII)	18293	(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl (2R,3S)-3-(4-fluorophenyl)morpholinyl ether; (2R,3S)-2-([(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]oxy)-3-(4-fluorophenyl)morpholine	171482-05-6	C₂₀H₁₈F₇NO₂	详情	详情
(XXXV)	50923	1,4-Dichloro-2-butyne	821-10-3	C₄H₄Cl₂	详情	详情
(XXXVI)	53302	(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl (2R,3S)-4-(4-chloro-2-butynyl)-3-(4-fluorophenyl)morpholinyl ether; (2R,3S)-2-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-(4-chloro-2-butynyl)-3-(4-fluorophenyl)morpholine	n/a	C₂₄H₂₁ClF₇NO₂	详情	详情
(XXXVII)	53303	(2R,3S)-4-(4-azido-2-butynyl)-2-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-3-(4-fluorophenyl)morpholine; (2R,3S)-4-(4-azido-2-butynyl)-3-(4-fluorophenyl)morpholinyl (1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl ether	n/a	C₂₄H₂₁F₇N₄O₂	详情	详情

Extended Information