-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】N1-[3-[2-Amino-1(S)-(biphenyl-4-ylmethyl)-2-oxoethylamino]-1(S)-benzyl-2(S)-hydroxypropyl]-N2-(pyridin-2-ylcarbonyl)-L-valinamide

【CA登记号】

【分子式】C₃₆H₄₁N₅O₄

【分子量】607.75927

【开发单位】Medivir (Originator), Uppsala University (Originator)

【药理作用】ANTIINFECTIVE THERAPY, Antimalarials, Treatment of Protozoal Diseases, Plasmepsin I Inhibitors, Plasmepsin II Inhibitors

合成路线1 合成路线2

合成路线1

Coupling between epoxide (I) and amine (II) affords amino alcohol (III). The amino group of (III) is then protected with benzyl chloroformate to provide carbamate (IV). Removal of the N-Boc group of (IV) with trifluoroacetic acid yields amine (V), which is subsequently coupled with N-Boc-L-valine (VI) by means of TBTU to furnish amide (VII). After acidic Boc group cleavage in (VII), the resultant amine (VIII) is acylated by picolinic acid (IX) producing amide (X).

参考文献中间体

【1】 Noteberg, D.; et al.; New antimalarials: Design and synthesis of protease inhibitors with effect in cultured parasite-infected human erythrocytes. Drugs Fut 2002, 27, Suppl. A.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	23444	tert-butyl (1S)-1-[(2R)oxiranyl]-2-phenylethylcarbamate	C₁₅H₂₁NO₃	详情	详情
(II)	58402	(2S)-2-amino-3-(4-bromophenyl)propanamide	C₉H₁₁BrN₂O	详情	详情
(III)	58396	tert-butyl (1S,2S)-3-{[(1S)-2-amino-1-(4-bromobenzyl)-2-oxoethyl]amino}-1-benzyl-2-hydroxypropylcarbamate	C₂₄H₃₂BrN₃O₄	详情	详情
(IV)	58397	benzyl (1S)-2-amino-1-(4-bromobenzyl)-2-oxoethyl{(2S,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-4-phenylbutyl}carbamate	C₃₂H₃₈BrN₃O₆	详情	详情
(V)	58398	benzyl (1S)-2-amino-1-(4-bromobenzyl)-2-oxoethyl[(2S,3S)-3-amino-2-hydroxy-4-phenylbutyl]carbamate	C₂₇H₃₀BrN₃O₄	详情	详情
(VI)	19733	(2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid	C₁₀H₁₉NO₄	详情	详情
(VII)	58399	benzyl (1S)-2-amino-1-(4-bromobenzyl)-2-oxoethyl[(2S,3S)-3-({(2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutanoyl}amino)-2-hydroxy-4-phenylbutyl]carbamate	C₃₇H₄₇BrN₄O₇	详情	详情
(VIII)	58400	benzyl (1S)-2-amino-1-(4-bromobenzyl)-2-oxoethyl((2S,3S)-3-{[(2S)-2-amino-3-methylbutanoyl]amino}-2-hydroxy-4-phenylbutyl)carbamate	C₃₂H₃₉BrN₄O₅	详情	详情
(IX)	59950	(chloromethyl)(dimethyl)silyl isopropyl ether; (chloromethyl)(isopropoxy)dimethylsilane	C₆H₁₅ClOSi	详情	详情
(X)	58401	benzyl (1S)-2-amino-1-(4-bromobenzyl)-2-oxoethyl[(2S,3S)-2-hydroxy-3-({(2S)-3-methyl-2-[(2-pyridinylcarbonyl)amino]butanoyl}amino)-4-phenylbutyl]carbamate	C₃₈H₄₂BrN₅O₆	详情	详情

合成路线2

The N-carbobenzoxy group of (X) is then removed by treatment with triflic acid, yielding (XI). Finally, Suzuki coupling of the aryl bromide (XI) with phenylboronic acid leads to the title biphenyl derivative.

参考文献中间体

【1】 Noteberg, D.; et al.; New antimalarials: Design and synthesis of protease inhibitors with effect in cultured parasite-infected human erythrocytes. Drugs Fut 2002, 27, Suppl. A.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	58401	benzyl (1S)-2-amino-1-(4-bromobenzyl)-2-oxoethyl[(2S,3S)-2-hydroxy-3-({(2S)-3-methyl-2-[(2-pyridinylcarbonyl)amino]butanoyl}amino)-4-phenylbutyl]carbamate		C₃₈H₄₂BrN₅O₆	详情	详情
(XI)	58403	N-((1S)-1-{[((1S,2S)-3-{[(1S)-2-amino-1-(4-bromobenzyl)-2-oxoethyl]amino}-1-benzyl-2-hydroxypropyl)amino]carbonyl}-2-methylpropyl)-2-pyridinecarboxamide		C₃₀H₃₆BrN₅O₄	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)