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【结 构 式】

【分子编号】26160

【品名】tert-butyl(dimethyl)silyl (2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphino]oxy]phenyl)propanoate

【CA登记号】

【 分 子 式 】C31H40NO6PSi

【 分 子 量 】581.721002

【元素组成】C 64.01% H 6.93% N 2.41% O 16.5% P 5.32% Si 4.83%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(II)

Reaction of N-acetyl-L-tyrosine (I) with tert-butyldimethylsilyl chloride and N-methylmorpholine (NMM), followed by phosphitylation with dibenzyldiisopropylamine phosphoramidite produced the intermediate phosphite ester (II), which was oxidized to phosphate (III) using tert-butyl hydroperoxide. Subsequent coupling of (III) with protected glutamic acid (IV) in the presence of DCC and HOBt afforded dipeptide (V). Deprotection of the allyl ester of (V) by means of Pd(PPh3)4 and pyrrolidine provided acid (VI). After conversion of (VI) to the corresponding mixed anhydride with isobutyl chloroformate, condensation with 4-methoxybenzyl amine (VII) yielded amide (VIII). Finally, the benzyl ester groups were eliminated by catalytic hydrogenation over Pd/C (1).

1 Llinas-Brunet, M.; et al.; Phosphotyrosine-containing dipeptides as high-affinity ligands for the p56lck SH2 domain. J Med Chem 1999, 42, 4, 722.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
40669   C17H22NO2P 详情 详情
(I) 26159 N-Acetyl-L-tyrosine; (2S)-2-(acetamido)-3-(4-hydroxyphenyl)propionic acid 537-55-3 C11H13NO4 详情 详情
(II) 26160 tert-butyl(dimethyl)silyl (2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphino]oxy]phenyl)propanoate C31H40NO6PSi 详情 详情
(III) 26161 (2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphoryl]oxy]phenyl)propionic acid C25H26NO7P 详情 详情
(IV) 26162 1-allyl 5-benzyl (2S)-2-aminopentanedioate C15H19NO4 详情 详情
(V) 26163 1-allyl 5-benzyl (2S)-2-[[(2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphoryl]oxy]phenyl)propanoyl]amino]pentanedioate C40H43N2O10P 详情 详情
(VI) 26164 (2S)-2-[[(2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphoryl]oxy]phenyl)propanoyl]amino]-5-(benzyloxy)-5-oxopentanoic acid C37H39N2O10P 详情 详情
(VII) 15098 4-Methoxybenzylamine; (4-Methoxyphenyl)methanamine 2393-23-9 C8H11NO 详情 详情
(VIII) 26165 benzyl (4S)-4-[[(2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphoryl]oxy]phenyl)propanoyl]amino]-5-[(4-methoxybenzyl)amino]-5-oxopentanoate C45H48N3O10P 详情 详情

合成路线2

该中间体在本合成路线中的序号:(IX)

Reaction of N-acetyl-L-tyrosine (VIII) with tert-butyldimethylsilyl chloride and N-methylmorpholine (NMM), followed by phosphitylation with dibenzyldiisopropylamine phosphoramidite produced the intermediate phosphite ester (IX), which was oxidized to phosphate (X) using tert-butyl hydroperoxide. Subsequent coupling of (X) with protected leucine (XI) in the presence of DCC and HOBt afforded dipeptide (XII). Deprotection of the allyl ester of (XII) by means of Pd(PPh3)4 and pyrrolidine provided acid (XIII). After conversion of (XIII) to the corresponding mixed anhydride with isobutyl chloroformate, condensation with the chiral amine (VII) yielded amide (XIV). Finally, the benzyl ester groups of (XIV) were eliminated by catalytic hydrogenation over Pd/C.

1 Llinas-Brunet, M.; et al.; Phosphotyrosine-containing dipeptides as high-affinity ligands for the p56lck SH2 domain. J Med Chem 1999, 42, 4, 722.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
40669   C17H22NO2P 详情 详情
(VII) 26171 (1S)-1-(4-isopropylphenyl)ethylamine; (1S)-1-(4-isopropylphenyl)-1-ethanamine C11H17N 详情 详情
(VIII) 26159 N-Acetyl-L-tyrosine; (2S)-2-(acetamido)-3-(4-hydroxyphenyl)propionic acid 537-55-3 C11H13NO4 详情 详情
(IX) 26160 tert-butyl(dimethyl)silyl (2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphino]oxy]phenyl)propanoate C31H40NO6PSi 详情 详情
(X) 26161 (2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphoryl]oxy]phenyl)propionic acid C25H26NO7P 详情 详情
(XI) 26172 allyl (2S)-2-amino-4-methylpentanoate C9H17NO2 详情 详情
(XII) 26173 allyl (2S)-2-[[(2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphoryl]oxy]phenyl)propanoyl]amino]-4-methylpentanoate C34H41N2O8P 详情 详情
(XIII) 26174 (2S)-2-[[(2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphoryl]oxy]phenyl)propanoyl]amino]-4-methylpentanoic acid C31H37N2O8P 详情 详情
(XIV) 26175 4-((2S)-2-(acetamido)-3-[[(1S)-1-([[(1S)-1-(4-isopropylphenyl)ethyl]amino]carbonyl)-3-methylbutyl]amino]-3-oxopropyl)phenyl dibenzyl phosphate C42H52N3O7P 详情 详情
Extended Information