(2S)-3-[4-(benzyloxy)phenyl]-2-[(tert-butoxycarbonyl)amino]propionic acid -Drug Synthesis Database

【结构式】

【分子编号】30396

【品名】(2S)-3-[4-(benzyloxy)phenyl]-2-[(tert-butoxycarbonyl)amino]propionic acid

【CA登记号】54784-43-9

【分子式】C₂₁H₂₅NO₅

【分子量】371.43324

【元素组成】C 67.91% H 6.78% N 3.77% O 21.54%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(I)

Coupling of N-Boc-O-benzyl-L-tyrosine (I) with tert-butylamine by means of O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU) afforded amide (II). Subsequent acid cleavage of the Boc group of (II) gave O-benzyltyrosine tert-butyl amide (III).

参考文献中间体

合成目标

【1】 Ryder, T.R.; et al.; Multiple parallel synthesis of N,N-dialkyldipeptidylamines as N-type calcium channel blockers. Bioorg Med Chem Lett 1999, 9, 13, 1813.
【2】 Szoke, B.G.; Rafferty, M.F.; Silva, D.F.; Song, Y.; Malone, T.C.; Hu, L.-Y.; Urge, L.; Nadasdi, L.; Ryder, T.R. (Neurex Corp.; Pfizer Inc.); Substd. peptidylamine calcium channel blockers. WO 9854123 .

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)	30396	(2S)-3-[4-(benzyloxy)phenyl]-2-[(tert-butoxycarbonyl)amino]propionic acid	54784-43-9	C₂₁H₂₅NO₅	详情	详情
(II)	30797	tert-butyl (1S)-1-[4-(benzyloxy)benzyl]-2-(tert-butylamino)-2-oxoethylcarbamate		C₂₅H₃₄N₂O₄	详情	详情
(III)	30798	(2S)-2-amino-3-[4-(benzyloxy)phenyl]-N-(tert-butyl)propanamide		C₂₀H₂₆N₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

The precursor amino acid derivatives were obtained as follows: The condensation of N-Boc-O-benzyltyrosine (I) with tert-butylamine using O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU) gave amide (II). Subsequent deprotection of the Boc group of (II) by means of trifluoroacetic acid provided O-benzyltyrosine tert-butyl amide (III). N-Methyl leucine benzyl ester (IV) was alkylated with 3-bromocyclohexene (V), yielding the cyclohexenyl amine (VI). Hydrogenation of the olefinic double bond of (VI) with concomitant benzyl ester hydrogenolysis in the presence of Pd/C furnished N-cyclohexyl-N-methylleucine (VII). The title dipeptide was finally obtained by HBTU-promoted coupling of amino acids (III) and (VII).

参考文献中间体

合成目标

【1】 Ryder, T.R.; Hu, L.-Y.; Rafferty, M.F.; et al.; N,N-dialkyl-dipeptidylamines as novel N-type calcium channel blockers. Bioorg Med Chem Lett 1999, 9, 6, 907.
【2】 Szoke, B.G.; Rafferty, M.F.; Silva, D.F.; Song, Y.; Malone, T.C.; Hu, L.-Y.; Urge, L.; Nadasdi, L.; Ryder, T.R. (Neurex Corp.; Pfizer Inc.); Substd. peptidylamine calcium channel blockers. WO 9854123 .

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)	30396	(2S)-3-[4-(benzyloxy)phenyl]-2-[(tert-butoxycarbonyl)amino]propionic acid	54784-43-9	C₂₁H₂₅NO₅	详情	详情
(II)	30797	tert-butyl (1S)-1-[4-(benzyloxy)benzyl]-2-(tert-butylamino)-2-oxoethylcarbamate		C₂₅H₃₄N₂O₄	详情	详情
(III)	30798	(2S)-2-amino-3-[4-(benzyloxy)phenyl]-N-(tert-butyl)propanamide		C₂₀H₂₆N₂O₂	详情	详情
(IV)	30799	benzyl (2S)-4-methyl-2-(methylamino)pentanoate		C₁₄H₂₁NO₂	详情	详情
(V)	30800	3-bromo-1-cyclohexene	1521-51-3	C₆H₉Br	详情	详情
(VI)	30801	benzyl (2S)-2-[2-cyclohexen-1-yl(methyl)amino]-4-methylpentanoate		C₂₀H₂₉NO₂	详情	详情
(VII)	30802	(2S)-2-[cyclohexyl(methyl)amino]-4-methylpentanoic acid		C₁₃H₂₅NO₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Coupling of N-Boc-O-benzyltyrosine (I) with 4-fluoro-1,2-phenylenediamine (II) by means of EDC afforded amide (III), which was converted into thioamide (IV) upon treatment with phosphorus pentasulfide and Na2CO3. Then, ring closure of (IV) with phosgene afforded the benzimidazolone derivative (V).

参考文献中间体

合成目标

【1】 Zackarie, B.; et al.; Thioamides: Synthesis, stability, and immunological activities of thioanalogues of imreg. Preparation Of new thioacylating agents using fluorobenzimidazolone derivatives. J Med Chem 1999, 42, 11, 2046.

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)	30396	(2S)-3-[4-(benzyloxy)phenyl]-2-[(tert-butoxycarbonyl)amino]propionic acid	54784-43-9	C₂₁H₂₅NO₅	详情	详情
(II)	30397	2-amino-4-fluorophenylamine; 4-fluoro-1,2-benzenediamine	367-31-7	C₆H₇FN₂	详情	详情
(III)	30398	tert-butyl (1S)-2-(2-amino-5-fluoroanilino)-1-[4-(benzyloxy)benzyl]-2-oxoethylcarbamate		C₂₇H₃₀FN₃O₄	详情	详情
(IV)	30399	tert-butyl (1S)-2-(2-amino-5-fluoroanilino)-1-[4-(benzyloxy)benzyl]-2-thioxoethylcarbamate		C₂₇H₃₀FN₃O₃S	详情	详情
(V)	30400	tert-butyl (1S)-1-[4-(benzyloxy)benzyl]-2-(6-fluoro-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-2-thioxoethylcarbamate		C₂₈H₂₈FN₃O₄S	详情	详情

合成路线4

该中间体在本合成路线中的序号：(I)

N-Boc-O-benzyltyrosine (I) was converted to the aminoalcohol derivative (III) via conversion to the mixed anhydride (II) with isobutyl chloroformate and subsequent reduction with NaBH4. Acid cleavage of the N-Boc protecting group of (III) gave the free amine (IV), which was acylated with oleoyl chloride (V) to afford amide (VI). Phosphitylation of (VI) with N,N-diisopropyl di-tert-butyl phosphoroamidite in the presence of tetrazole, followed by oxidation of the intermediate phosphite with hydrogen peroxide, furnished the phosphate (VII). The tert-butyl phosphate ester groups of (VII) were finally cleaved by treatment with trifluoroacetic acid.

参考文献中间体

合成目标

【1】 Santos, W.L.; et al.; Structure-activity relationships of lysophosphatidic acid: Synthesis and analysis of EDG receptor agonists and antagonists. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 272.

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)	30396	(2S)-3-[4-(benzyloxy)phenyl]-2-[(tert-butoxycarbonyl)amino]propionic acid	54784-43-9	C₂₁H₂₅NO₅	详情	详情
(II)	51294			C₂₆H₃₃NO₇	详情	详情
(III)	21589	ethyl 3-cyano-3-[3-(cyclopentyloxy)-4-methoxyphenyl]propanoate		C₁₈H₂₃NO₄	详情	详情
(IV)	51290	(2S)-2-amino-3-[4-(benzyloxy)phenyl]-1-propanol		C₁₆H₁₉NO₂	详情	详情
(V)	51291	(Z)-9-hexadecenoyl chloride		C₁₆H₂₉ClO	详情	详情
(VI)	51292	(Z)-N-[(1S)-1-[4-(benzyloxy)benzyl]-2-hydroxyethyl]-9-hexadecenamide		C₃₂H₄₇NO₃	详情	详情
(VII)	51293	(2S)-3-[4-(benzyloxy)phenyl]-2-[(Z)-9-hexadecenoylamino]propyl di(tert-butyl) phosphate		C₄₀H₆₄NO₆P	详情	详情

Extended Information