Maraviroc, UK-427857, Selzentry, Celsentri, -Drug Synthesis Database

【结构式】

【药物名称】Maraviroc, UK-427857, Selzentry, Celsentri

【化学名称】4,4-Difluoro-N-[3-[(1R,3exo,5S)-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]oct-8-yl]-1(S)-phenylpropyl] cyclohexanecarboxamide

【CA登记号】376348-65-1

【分子式】C₂₉H₄₁F₂N₅O

【分子量】513.6729

【开发单位】Pfizer, Inc. (US).

【药理作用】Anti-HIV Agent, Viral Entry Inhibitor, Chemokine CCR5 Antagonist

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】 Haycock-Lewandowski SJ, Wilder A, Ahman J. 2008. Development of a bulk enabling route to maraviroc (UK-427, 857), a CCR-5 receptor antagonist. Organic Process Research & Development, 12(6): 1094～1103.
【2】 Tung R. 2008. Preparation of deuterated triazolyl tropane derivatives as CCR5 receptor inhibitors. WO 2008063600.

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)	67255	(S)-methyl 3-amino-3-phenylpropanoate (2R,3S)-2,3-dihydroxysuccinate		C₁₄H₁₉NO₈	详情	详情
(I)	67247	8-benzyl-8-azabicyclo[3.2.1]octan-3-one	28957-72-4	C₁₄H₁₇NO	详情	详情
(II)	67248	8-benzyl-8-azabicyclo[3.2.1]octan-3-one oxime	76272-34-9	C₁₄H₁₈N₂O	详情	详情
(III)	67249	8-benzyl-8-azabicyclo[3.2.1]octan-3-amine		C₁₄H₂₀N₂	详情	详情
(IV)	67251	N-(8-benzyl-8-azabicyclo[3.2.1]octan-3-yl)isobutyramide	376348-67-3	C₁₈H₂₆N₂O	详情	详情
(V)	67252	8-benzyl-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane		C₂₀H₂₈N₄	详情	详情
(VI)	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(VII)	67253	3-(2-isopropyl-5-methyl-1H-pyrrol-1-yl)-8-azabicyclo[3.2.1]octane		C₁₅H₂₄N₂	详情	详情
(VIII)	12963	Malonic acid	141-82-2	C₃H₄O₄	详情	详情
(IX)	59224	3-(3-Aminophenyl)propionic acid; beta-Aminohydrocinnamic acid; DL-3-Amino-3-phenylpropionic acid; 3-Amino-3-phenylpropionic acid	614-19-7	C₉H₁₁NO₂	详情	详情
(X)	67254	methyl 3-amino-3-phenylpropanoate		C₁₀H₁₃NO₂	详情	详情
(XII)	67256	(S)-methyl 3-(((benzyloxy)carbonyl)amino)-3-phenylpropanoate		C₁₈H₁₉NO₄	详情	详情
(XIII)	67257	(S)-3-(((benzyloxy)carbonyl)amino)-3-phenylpropanoic acid		C₁₇H₁₇NO₄	详情	详情
(XIV)	67258	(S)-benzyl (3-hydroxy-1-phenylpropyl)carbamate		C₁₇H₁₉NO₃	详情	详情
(XV)	67259	(S)-benzyl (3-oxo-1-phenylpropyl)carbamate		C₁₇H₁₇NO₃	详情	详情
(XVI)	67260	benzyl ((1S)-3-(3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropyl)carbamate		C₃₀H₃₉N₅O₂	详情	详情
(XVII)	67261	(1S)-3-(3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropan-1-amine		C₂₂H₃₃N₅	详情	详情
(XVIII)	67262	4,4-difluorocyclohexanecarbonyl chloride		C₇H₉ClF₂O	详情	详情
(XX)	67250	8-benzyl-8-azabicyclo[3.2.1]octan-3-amine		C₁₄H₂₀N₂	详情	详情

合成路线2

参考文献中间体

【1】 Ahman J, Birch M, Haycock-Lewandowski, et al. 2008. Process research and scale-up of a commercializable route to maraviroc(UK-427, 857), a CCR-5 receptor antagonist. Organic Process Research & Development, 12(6): 1104～1113.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(II)	67263	3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane 4-methylbenzenesulfonate	C₇H₈O₃S.C₁₃H₂₂N₄	详情	详情
(IV)	67262	4,4-difluorocyclohexanecarbonyl chloride	C₇H₉ClF₂O	详情	详情
(V)	67264	methyl 3-(4,4-difluorocyclohexanecarboxamido)-3-phenylpropanoate	C₁₇H₂₁F₂NO₃	详情	详情
(I)	67252	8-benzyl-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane	C₂₀H₂₈N₄	详情	详情
(III)	67254	methyl 3-amino-3-phenylpropanoate	C₁₀H₁₃NO₂	详情	详情
(VI)	67265	4,4-difluoro-N-(3-hydroxy-1-phenylpropyl)cyclohexanecarboxamide	C₁₆H₂₁F₂NO₂	详情	详情
(VII)	67266	4,4-difluoro-N-(3-oxo-1-phenylpropyl)cyclohexanecarboxamide	C₁₆H₁₉F₂NO₂	详情	详情

合成路线3

参考文献中间体

【1】 Price DA, Gayton S, Selby MD, et al. 2005. Initial synthesis of UK-427, 857(maraviroc). Tetrahedron Letters, 46(30): 5005～5007.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	67269	(S)-tert-butyl (3-oxo-1-phenylpropyl)carbamate	135865-78-0	C₁₄H₁₉NO₃	详情	详情
(VI)	67261	(1S)-3-(3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropan-1-amine		C₂₂H₃₃N₅	详情	详情
(I)	67267	methyl 3-amino-3-phenylpropanoate		C₁₀H₁₃NO₂	详情	详情
(II)	67268	(S)-methyl 3-((tert-butoxycarbonyl)amino)-3-phenylpropanoate		C₁₅H₂₁NO₄	详情	详情
(IV)	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(V)	67270	tert-butyl ((1S)-3-(3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropyl)carbamate		C₂₇H₄₁N₅O₂	详情	详情
(VII)	67271	4,4-difluorocyclohexanecarboxylic acid	122665-97-8	C₇H₁₀F₂O₂	详情	详情

合成路线4

参考文献中间体

【1】 Lou S, Moquist PN, Schaus SE. 2007. Asymmetric allylboration of acyl imines catalyzed by chiral diols. Journal of the American Chemical Society, 129(49): 15398～15404.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	10507	Trimethyl-N-[(E)-benzylidene]silanamine; N-[(E)-Benzylidene]-N-(trimethylsilyl)amine	17599-61-0	C₁₀H₁₅NSi	详情	详情
(I)	67271	4,4-difluorocyclohexanecarboxylic acid	122665-97-8	C₇H₁₀F₂O₂	详情	详情
(II)	29841	Oxalyl chloride; 2-Chloro-2-oxoacetyl chloride	79-37-8	C₂Cl₂O₂	详情	详情
(IV)	67272	(E)-N-benzylidene-4,4-difluorocyclohexanecarboxamide		C₁₄H₁₅F₂NO	详情	详情
(V)	67273	diisopropyl allylboronate	51851-79-7	C₉H₁₉BO₂	详情	详情
(VI)	67274	3,3'-diphenyl-[1,1'-binaphthalene]-2,2'-diol		C₃₂H₂₂O₂	详情	详情
(VII)	67275	(E)-4,4-difluoro-N-(1-phenylbut-3-en-1-ylidene)cyclohexanecarboxamide		C₁₇H₁₉F₂NO	详情	详情
(VIII)	67276	(E)-4,4-difluoro-N-(3-oxo-1-phenylpropylidene)cyclohexanecarboxamide		C₁₆H₁₇F₂NO₂	详情	详情
(IX)	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(2)