chloro[(1R,2R,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl][(1S,2S,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]borane -Drug Synthesis Database

【结构式】

【分子编号】45693

【品名】chloro[(1R,2R,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl][(1S,2S,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]borane

【CA登记号】

【分子式】C₂₀H₃₄BCl

【分子量】320.75366

【元素组成】C 74.89% H 10.68% B 3.37% Cl 11.05%

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：(VIII)

The chiral (R)-(+)-epoxide (X) was synthesized by asymmetric reduction of 3-bromotrifluoroacetone (VII) using (+)-B-chlorodiisopinocampheylborane (VIII), followed by intramolecular cyclization of the resulting (R)-bromohydrin (VIII) in aqueous NaOH. Finally, reaction of amine (IV) with the chiral epoxide (X) furnished the desired enantiomer.

参考文献中间体

合成目标

【1】 Durley, R.C.; et al.; Chiral N,N-disubstituted trifluoro-3-amino-2-propanols are potent inhibitors of cholesteryl ester transfer protein. J Med Chem 2002, 45, 18, 3891.
【2】 Grapperhaus, M.L.; Hickory, B.S.; Sikorski, J.A.; Wang, L.J.; Massa, M.A.; Mischke, D.A.; Honda, D.D.; New simple class of potent cholesteryl ester transfer protein inhibitors. 220th ACS Natl Meet (Aug 20 2000, Washington DC) 2000, Abst MEDI 283.
【3】 Durley, R.C.; et al.; Discovery of chiral N,N-disubstituted trifluoro-3-amino-2-propanols as potent inhibitors of cholesteryl ester transfer protein. J Med Chem 2000, 43, 24, 4575.
【4】 Vernier, W.F.; Wang, L.; Mischke, D.A.; Hamme, A.T.; Promo, M.A.; Sikorski, J.A.; Spangler, D.P.; Grapperhaus, M.L.; Massa, M.A.; Durley, R.C.; Reinhard, E.J.; Fobian, Y.M.; Hickory, B.S.; Tollefson, M.B.; Norton, M.B.; Rueppel, M.L. (Pharmacia Corp.); (R)-Chiral halogenated 1-substd.amino-(n+1)-alkanols useful for inhibiting cholesteryl ester transfer protein activity. WO 0018721; WO 0018724 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	45687	N-(3-phenoxyphenyl)-N-[3-(1,1,2,2-tetrafluoroethoxy)benzyl]amine; 3-phenoxy-N-[3-(1,1,2,2-tetrafluoroethoxy)benzyl]aniline		C₂₁H₁₇F₄NO₂	详情	详情
(VII)	39909	3-bromo-1,1,1-trifluoroacetone	431-35-6	C₃H₂BrF₃O	详情	详情
(VIII)	45693	chloro[(1R,2R,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl][(1S,2S,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]borane		C₂₀H₃₄BCl	详情	详情
(IX)	45694	(2S)-3-bromo-1,1,1-trifluoro-2-propanol	88378-50-1	C₃H₄BrF₃O	详情	详情
(X)	45689	(2R)-2-(trifluoromethyl)oxirane		C₃H₃F₃O	详情	详情

Extended Information