Cinacalcet hydrochloride, KRN-1493, AMG-073.HCl, Sensipar, -Drug Synthesis Database

【结构式】

【药物名称】Cinacalcet hydrochloride, KRN-1493, AMG-073.HCl, Sensipar

【化学名称】N-[1(R)-(1-Naphthyl)ethyl]-N-[3-[3-(trifluoromethyl)phenyl]propyl]amine hydrochloride

【CA登记号】364782-34-3, 226256-56-0 (free base)

【分子式】C₂₂H₂₃ClF₃N

【分子量】393.88351

【开发单位】Amgen (Orphan Drug), NPS Allelix (Originator), Amgen (Licensee), Kirin Brewery (Licensee)

【药理作用】Bone Diseases, Treatment of, ENDOCRINE DRUGS, METABOLIC DRUGS, Renal Failure, Agents for, RENAL-UROLOGIC DRUGS, Thyroid Disease Therapy, Treatment of Hypercalcemia, Treatment of Hyperparathyroidism, Treatment of Renal Diseases

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

参考文献中间体

【1】 Van Wagenen BC,Moe ST,et al.2001.Prepantion of l-arylethylamines as calcium receptor ligands US 6211244
【2】 Wang X,ChenY,et aL 2004.Synthesis of cirutcalcet congeners Tetrahedron Lett, 45: 8355-8358

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
（V）	11413	1-(2-Naphthyl)-1-ethanone; Methyl 2-naphthyl ketone	93-08-3	C₁₂H₁₀O	详情	详情
(I)	66196	2-Propenoyl chloride,3-[3-(trifluoromethyl)phenyl]-, (2E)-;2-Propenoylchloride, 3-[3-(trifluoromethyl)phenyl]-, (E)-;(E)-3-Trifluoromethylcinnamoylchloride;trans-3-(Trifluoromethyl)cinnamic acid chloride;trans-3-(Trifluoromethyl)cinnamoyl chloride;trans-3-[3-(Trifluoromethyl)phenyl]-2-propenoyl chloride	64379-91-5	C₁₀H₆ClF₃O	详情	详情
(II)	66197	2-Propenamide,3-[3-(trifluoromethyl)phenyl]-, (2E)-;2-Propenamide,3-[3-(trifluoromethyl)phenyl]-, (E)-	64380-24-1	C₁₀H₈F₃NO	详情	详情
(III)	66198	3-(3-(trifluoromethyl)phenyl)propanamide		C₁₀H₁₀F₃NO	详情	详情
(IV)	66199	3-(3-(trifluoromethyl)phenyl)propan-1-amine		C₁₀H₁₂F₃N	详情	详情
(VI)	66200	(E)-N-(1-(naphthalen-1-yl)ethylidene)-3-(3-(trifluoromethyl)phenyl)propan-1-amine		C₂₂H₂₀F₃N	详情	详情
(VII)	66201	(R)-N-(1-(naphthalen-1-yl)ethyl)-3-(3-(trifluoromethyl)phenyl)propan-1-amine		C₂₂H₂₂F₃N	详情	详情

合成路线2

参考文献中间体

【1】 Van Wagenen BC.Moe ST,et aL 2001.Pteparationof l-arldethyttunines as.calcium receptor ligands US 6211244

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
（I）	66202	3-(3-TRIFLUOROMETHYL-PHENYL)-PROPIONITRILE	95096-06-3	C₁₀H₈F₃N	详情	详情
(II)	66203	(E)-di-tert-butyl((3-(3-(trifluoromethyl)phenyl)propylidene)amino)aluminum		C₁₈H₂₇AlF₃N	详情	详情
(III)	17443	(1R)-1-(1-naphthyl)ethylamine; (1R)-1-(1-naphthyl)-1-ethanamine	3886-70-2	C₁₂H₁₃N	详情	详情
(IV)	55376	N-[(1R)-1-(1-naphthyl)ethyl]-N-{(E)-3-[3-(trifluoromethyl)phenyl]propylidene}amine; (1R)-1-(1-naphthyl)-N-{(E)-3-[3-(trifluoromethyl)phenyl]propylidene}-1-ethanamine		C₂₂H₂₀F₃N	详情	详情

合成路线3

参考文献中间体

【1】 Lifshitz Liron R． Eisenstadt A, et aL 2006. Process for preparing cinacalcet from 3-(3-trifluoromethylphenyl) propanol. W0 2006125026

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
（V）	66204	3-(3-(trifluoromethyl)phenyl)propan-1-ol		C₁₀H₁₁F₃O	详情	详情
(I)	26348	1-bromo-3-(trifluoromethyl)benzene; 3-Bromobenzotrifluoride	401-78-5	C₇H₄BrF₃	详情	详情
(II)	10164	ethyl acrylate	140-88-5	C₅H₈O₂	详情	详情
(III)	42936	ethyl (E)-3-[3-(trifluoromethyl)phenyl]-2-propenoate	113048-68-3	C₁₂H₁₁F₃O₂	详情	详情
(IV)	42937	(E)-3-[3-(trifluoromethyl)phenyl]-2-propen-1-ol		C₁₀H₉F₃O	详情	详情
(VI)	66205	3-(3-(trifluoromethyl)phenyl)propyl methanesulfonate		C₁₁H₁₃F₃O₃S	详情	详情
(VII)	17443	(1R)-1-(1-naphthyl)ethylamine; (1R)-1-(1-naphthyl)-1-ethanamine	3886-70-2	C₁₂H₁₃N	详情	详情

合成路线4

Reaction of 1(R)-(1-naphthyl)ethylamine (I) with 3-[3-(trifluoromethyl)phenyl]propionaldehyde (II) by means of titanium tetraisopropoxide gives the corresponding imine (III), which is finally reduced with NaBH3CN in ethanol.

参考文献中间体

【1】 Bayes, M.; Castaner, R.M.; Sorbera, L.A.; Cinacalcet Hydrochloride. Drugs Fut 2002, 27, 9, 831.
【2】 Moe, S.T.; Balandrin, M.F.; Van Wagenen, B.C.; Nemeth, E.F.; DelMar, E.G. (NPS Pharmaceuticals, Inc.); Calcium receptor-active cpds.. US 6211244 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	17443	(1R)-1-(1-naphthyl)ethylamine; (1R)-1-(1-naphthyl)-1-ethanamine	3886-70-2	C₁₂H₁₃N	详情	详情
(II)	55375	3-[3-(trifluoromethyl)phenyl]propanal		C₁₀H₉F₃O	详情	详情
(III)	55376	N-[(1R)-1-(1-naphthyl)ethyl]-N-{(E)-3-[3-(trifluoromethyl)phenyl]propylidene}amine; (1R)-1-(1-naphthyl)-N-{(E)-3-[3-(trifluoromethyl)phenyl]propylidene}-1-ethanamine		C₂₂H₂₀F₃N	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(2)