N-{[(1,1-dimethylethyl)oxy]carbonyl}-1-methylhistidine -Drug Synthesis Database

【结构式】

【分子编号】63382

【品名】N-{[(1,1-dimethylethyl)oxy]carbonyl}-1-methylhistidine

【CA登记号】

【分子式】C₁₂H₁₉N₃O₄

【分子量】269.30068

【元素组成】C 53.52% H 7.11% N 15.6% O 23.76%

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：(I)

The title compound has been synthesized by two related methods. Coupling of N-Boc-L-methylhistidine (I) with D-4-methoxyphenylalanine methyl ester (II) employing EDC/HOBt affords the protected dipeptide (III). Subsequent saponification of the methyl ester (III) leads to carboxylic acid (IV). This is then coupled to 4-butyryl-4-phenylpiperidine (V) to furnish amide (VI). Finally, acidic cleavage of the N-Boc protecting group of (VI) provides the title compound.

参考文献中间体

合成目标

【1】 Poindexter, G.S.; Ruediger, E.H.; Ruel, R.; Lawrence, R.M.; Yu, G.; Macor, J.; Morton, G.C.; Thibault, C.; Herpin, T. (Bristol-Myers Squibb Co.); Cpds. useful as modulators of melanocortin receptors and pharmaceutical compsns. comprising same. EP 1363631; EP 1363898; WO 0270511; WO 0279146 .
【2】 Macor, J.E.; Carlson, K.E. (Bristol-Myers Squibb Co.); Co-administration of melanocortin receptor agonists and phosphodiesterase inhibitor for treatment of cyclic-AMP associated disorders. WO 0269905 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	63382	N-{[(1,1-dimethylethyl)oxy]carbonyl}-1-methylhistidine	C₁₂H₁₉N₃O₄	详情	详情
(II)	32454	methyl (2S)-2-amino-3-(4-methoxyphenyl)propanoate	C₁₁H₁₅NO₃	详情	详情
(III)	63383	methyl 2-{[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-3-(1-methyl-1H-imidazol-5-yl)propanoyl]amino}-3-[4-(methyloxy)phenyl]propanoate	C₂₃H₃₂N₄O₆	详情	详情
(IV)	63384	N-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-3-(1-methyl-1H-imidazol-5-yl)propanoyl]-4-(methyloxy)phenylalanine	C₂₂H₃₀N₄O₆	详情	详情
(V)	63385	1-(4-phenyl-4-piperidinyl)-1-butanone	C₁₅H₂₁NO	详情	详情
(VI)	63386	1,1-dimethylethyl 2-[(2-(4-butanoyl-4-phenyl-1-piperidinyl)-1-{[4-(methyloxy)phenyl]methyl}-2-oxoethyl)amino]-1-[(1-methyl-1H-imidazol-5-yl)methyl]-2-oxoethylcarbamate	C₃₇H₄₉N₅O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Similarly, N-Boc-D-4-methoxyphenylalanine (I) is coupled to 4-butyryl-4-phenylpiperidine (II), yielding amide (III). After acidic Boc group cleavage in (III), the resultant amine (IV) is acylated by N-Boc-L-methylhistidine (V) to provide the dipeptide amide (VI). The N-Boc protecting group of (VI) is finally removed employing trifluoroacetic acid.

参考文献中间体

合成目标

【1】 Herpin, T.F.; Yu, G.; Carlson, K.E.; Morton, G.C.; Wu, X.; Kang, L.; Tuerdi, H.; Khanna, A.; Tokarski, J.S.; Lawrence, R.M.; Macor, J.E.; Discovery of tyrosine-based potent and selective melanocortin-1 receptor small-molecule agonists with anti-inflammatory properties. J Med Chem 2003, 46, 7, 1123.

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)	16875	(2S)-2-[(tert-Butoxycarbonyl)amino]-3-(4-methoxyphenyl)propionic acid; N-t-BOC-O-Methyl-L-tyrosine	53267-93-9	C₁₅H₂₁NO₅	详情	详情
(II)	63385	1-(4-phenyl-4-piperidinyl)-1-butanone		C₁₅H₂₁NO	详情	详情
(III)	63387	1,1-dimethylethyl 2-(4-butanoyl-4-phenyl-1-piperidinyl)-1-{[4-(methyloxy)phenyl]methyl}-2-oxoethylcarbamate		C₃₀H₄₀N₂O₅	详情	详情
(IV)	63388	1-(1-{2-amino-3-[4-(methyloxy)phenyl]propanoyl}-4-phenyl-4-piperidinyl)-1-butanone		C₂₅H₃₂N₂O₃	详情	详情
(V)	63382	N-{[(1,1-dimethylethyl)oxy]carbonyl}-1-methylhistidine		C₁₂H₁₉N₃O₄	详情	详情
(VI)	63386	1,1-dimethylethyl 2-[(2-(4-butanoyl-4-phenyl-1-piperidinyl)-1-{[4-(methyloxy)phenyl]methyl}-2-oxoethyl)amino]-1-[(1-methyl-1H-imidazol-5-yl)methyl]-2-oxoethylcarbamate		C₃₇H₄₉N₅O₆	详情	详情

Extended Information