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【结 构 式】

【分子编号】16255

【品名】tert-butyl (3S)-4-[(2S,4R)-5-amino-4-benzyl-2-hydroxy-5-oxopentyl]-3-[(tert-butylamino)carbonyl]tetrahydro-1(2H)-pyrazinecarboxylate

【CA登记号】

【 分 子 式 】C26H42N4O5

【 分 子 量 】490.64344

【元素组成】C 63.65% H 8.63% N 11.42% O 16.3%

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:(XVIII)

3) The alkylation of 5(S)-(tert-butyldimethylsilyloxymethyl)tetrahydrofuran-2-one (XII) by means of benzyl bromide (XIII) and lithium diisopropylamide (LDA) gives the corresponding 3(R)-benzyl derivative (XIV), which is deprotected with aqueous HF, yielding the hydroxymethyl compound (XV). The esterification of (XV) with trifluoromethanesulfonic anhydride affords the corresponding triflate (XVI), which is condensed with the chiral piperazine (VII) by means of diisopropylethylamine in isopropanol, giving the substituted furanone (XVII). Ring opening of the furanone (XVII) with LiOH, DME and imidazole yields the substituted hydroxypentanamide (XVIII), which is protected with tert-butyldimethylsilyl chloride to afford the protected amide (XIX). The trans-amidation of (XIX) with 2-hydroxyindan-1-amine (II) by means of 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) and 1-hydroxybenzotriazole (HOBt) in DMF gives the protected dihydroxy diamide (XX), which is deprotected with trimethylsilyl triflate, affording the dihydroxy diamide (VII), already obtained. This compound is then alkylated with 3-(chloromethyl)pyridine (IX) as before.

1 Mealy, N.; Castaner, J.; Indinavir Sulfate. Drugs Fut 1996, 21, 6, 600.
2 Vacca, J.P.; Holloway, M.K.; Dorsey, B.D.; Hungate, R.W.; Guare, J.P. (Merck & Co., Inc.); HIV protease inhibitors useful for the treatment of AIDS. EP 0541168; JP 1993279337; WO 9309096 .
3 Vacca, J.P.; Guare, J.P.; Dorsey, B.D.; Holloway, M.K.; Hungate, R.W. (Merck & Co., Inc.); HIV protease inhibitors in pharmaceutical combinations for the treatment of AIDS. EP 0617968; JP 1996508496; WO 9422480 .
4 Vacca, J.P.; Dorsey, B.D.; Guare, J.P.; Holloway, M.K.; Hungate, R.W.; Levin, R.B. (Merck & Co., Inc.); HIV protease inhibitors useful for the treatment of AIDS. EP 0696277; JP 1996509980; US 5413999; WO 9426717 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(II) 16239 (1S,2R)-1-amino-2,3-dihydro-1H-inden-2-ol; Cis-(1S)-1-amino-2,3-dihydro-1H-inden-2-ol 126456-43-7 C9H11NO 详情 详情
(VII) 16244 tert-butyl (3S)-3-[(tert-butylamino)carbonyl]tetrahydro-1(2H)-pyrazinecarboxylate 150323-35-6 C14H27N3O3 详情 详情
(VIII) 16245 (2S)-1-((2S,4R)-4-benzyl-2-hydroxy-5-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-5-oxopentyl)-N-(tert-butyl)-2-piperazinecarboxamide C30H42N4O4 详情 详情
(IX) 15793 3-(Chloromethyl)pyridine 3099-31-8 C6H6ClN 详情 详情
(XII) 16249 (5S)-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)dihydro-2(3H)-furanone C11H22O3Si 详情 详情
(XIII) 12912 1-(Bromomethyl)benzene; Alpha-bromotoluene 100-39-0 C7H7Br 详情 详情
(XIV) 16251 (3R,5S)-3-benzyl-5-([[tert-butyl(dimethyl)silyl]oxy]methyl)dihydro-2(3H)-furanone C18H28O3Si 详情 详情
(XV) 16252 (3R,5S)-3-benzyl-5-(hydroxymethyl)dihydro-2(3H)-furanone C12H14O3 详情 详情
(XVI) 16253 [(2S,4R)-4-benzyl-5-oxotetrahydro-2-furanyl]methyl trifluoromethanesulfonate C13H13F3O5S 详情 详情
(XVII) 16254 tert-butyl (3S)-4-[[(2S,4R)-4-benzyl-5-oxotetrahydro-2-furanyl]methyl]-3-[(tert-butylamino)carbonyl]tetrahydro-1(2H)-pyrazinecarboxylate C26H39N3O5 详情 详情
(XVIII) 16255 tert-butyl (3S)-4-[(2S,4R)-5-amino-4-benzyl-2-hydroxy-5-oxopentyl]-3-[(tert-butylamino)carbonyl]tetrahydro-1(2H)-pyrazinecarboxylate C26H42N4O5 详情 详情
(XIX) 16256 tert-butyl (3S)-4-((2S,4R)-5-amino-4-benzyl-2-[[tert-butyl(dimethyl)silyl]oxy]-5-oxopentyl)-3-[(tert-butylamino)carbonyl]-1-piperazinecarboxylate C32H56N4O5Si 详情 详情
(XX) 16257 tert-butyl (3S)-4-((2S,4R)-4-benzyl-2-[[tert-butyl(dimethyl)silyl]oxy]-5-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-5-oxopentyl)-3-[(tert-butylamino)carbonyl]-1-piperazinecarboxylate C41H64N4O6Si 详情 详情
(XXI) 16258 tert-butyl (3S)-4-((2S,4R)-4-benzyl-2-hydroxy-5-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-5-oxopentyl)-3-[(tert-butylamino)carbonyl]-1-piperazinecarboxylate C35H50N4O6 详情 详情
Extended Information