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【结 构 式】

【分子编号】38266

【品名】(2S)-N-[(1S,3S,4S)-1-benzyl-4-(dibenzylamino)-3-hydroxy-5-phenylpentyl]-3-methyl-2-[2-oxotetrahydro-1(2H)-pyrimidinyl]butanamide

【CA登记号】

【 分 子 式 】C41H50N4O3

【 分 子 量 】646.87316

【元素组成】C 76.13% H 7.79% N 8.66% O 7.42%

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:(X)

The reaction of L-phenylalanine (I) with benzyl bromide and K2CO3 in hot EtOH/H2O gives N,N,O-tribenzyl derivative (II), which is condensed with acetonitrile (III) by means of NaNH2 in THF yielding the pentanenitrile (IV). The reaction of nitrile (IV) with benzylmagnesium chloride (V) in THF affords the diphenylhexenone (VI), which is reduced with NaBH4 in THF to give the diphenylhexanol (VII) (slightly impurified (~10%) with other diastereomers that are not eliminated at this stage). The condensation of (VII) with acid chloride (VIII) (obtained by reaction of acid (IX) with SOCl2) in the presence of imidazole yields the amide (X), which is debenzylated with ammonium formate over Pd/C in methanol affording the amine (XI). At this stage the purification (elimination of the diastereomers) has been performed by crystallization of its salt with L-pyroglutamic acid (XII) in EtOH/DMF, pure salt (XIII) being obtained. Finally, this compound is condensed with the acid chloride (XIV) (obtained by reaction of acid (XV) with SOCl2) by means of NaHCO3 in ethyl acetate/water. The intermediates, the acids (IX) and (XV), have been obtained as indicated in schemes 24659001a and 24659001b (intermediates (XIII) and (X) of these schemes, respectively).

1 Stoner, E.J.; et al.; Synthesis of HIV protease inhibitor ABT-378 (lopinavir). Org Process Res Dev 2000, 4, 4, 264.
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) 13952 (S)-(-)-Phenylalanine; L-Phenylalanine 63-91-2 C9H11NO2 详情 详情
(II) 37670 benzyl (2S)-2-(dibenzylamino)-3-phenylpropanoate C30H29NO2 详情 详情
(III) 37210 acetonitrile 75-05-8 C2H3N 详情 详情
(IV) 38263 (4S)-4-(dibenzylamino)-3-oxo-5-phenylpentanenitrile C25H24N2O 详情 详情
(V) 18327 benzyl(chloro)magnesium 6921-34-2 C7H7ClMg 详情 详情
(VI) 37671 (2S,4E)-5-amino-2-(dibenzylamino)-1,6-diphenyl-4-hexen-3-one C32H32N2O 详情 详情
(VII) 37672 (2S,3S,5S)-5-amino-2-(dibenzylamino)-1,6-diphenyl-3-hexanol C32H36N2O 详情 详情
(VIII) 38265 (2S)-3-methyl-2-[2-oxotetrahydro-1(2H)-pyrimidinyl]butanoyl chloride C9H15ClN2O2 详情 详情
(IX) 38264 (2S)-3-methyl-2-[2-oxotetrahydro-1(2H)-pyrimidinyl]butyric acid C9H16N2O3 详情 详情
(X) 38266 (2S)-N-[(1S,3S,4S)-1-benzyl-4-(dibenzylamino)-3-hydroxy-5-phenylpentyl]-3-methyl-2-[2-oxotetrahydro-1(2H)-pyrimidinyl]butanamide C41H50N4O3 详情 详情
(XI) 38267 (2S)-N-[(1S,3S,4S)-4-amino-1-benzyl-3-hydroxy-5-phenylpentyl]-3-methyl-2-[2-oxotetrahydro-1(2H)-pyrimidinyl]butanamide C27H38N4O3 详情 详情
(XII) 32406 (2S)-5-oxo-2-pyrrolidinecarboxylic acid 98-79-3 C5H7NO3 详情 详情
(XIII) 38268 (2S,3S,5S)-3-hydroxy-5-([(2S)-3-methyl-2-[2-oxotetrahydro-1(2H)-pyrimidinyl]butanoyl]amino)-1,6-diphenyl-2-hexanaminium (2S)-5-oxo-2-pyrrolidinecarboxylate C32H45N5O6 详情 详情
(XIV) 38269 2-(2,6-dimethylphenoxy)acetyl chloride C10H11ClO2 详情 详情
(XV) 38270 2-(2,6-dimethylphenoxy)acetic acid C10H12O3 详情 详情
Extended Information