(2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphoryl]oxy]phenyl)propionic acid -Drug Synthesis Database

【结构式】

【分子编号】26161

【品名】(2S)-2-(acetamido)-3-(4-[[bis(benzyloxy)phosphoryl]oxy]phenyl)propionic acid

【CA登记号】

【分子式】C₂₅H₂₆NO₇P

【分子量】483.457742

【元素组成】C 62.11% H 5.42% N 2.9% O 23.17% P 6.41%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(III)

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).

参考文献中间体

合成目标

【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：(X)

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.

参考文献中间体

合成目标

【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