(2R)-N-[(1R)-1-benzyl-2-(methylamino)-2-oxoethyl]-N-methyl-2-(methylamino)-3-(2-naphthyl)propanamide -Drug Synthesis Database

【结构式】

【分子编号】27234

【品名】(2R)-N-[(1R)-1-benzyl-2-(methylamino)-2-oxoethyl]-N-methyl-2-(methylamino)-3-(2-naphthyl)propanamide

【CA登记号】

【分子式】C₂₅H₂₉N₃O₂

【分子量】403.52428

【元素组成】C 74.41% H 7.24% N 10.41% O 7.93%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XV)

Methylation of N-Boc-D-phenylalanine (VIII) with methyl iodide and NaH afforded the N-methyl amino acid (IX). After coupling with methylamine in the presence of EDC and HOBt, the Boc protecting group of the resulting amide (X) was removed by treatment with trifluoroacetic acid to give (XI). The N-methyl amino acid (XIII), prepared by methylation of N-Boc-naphthylalanine (XII), was then coupled to amine (XI) by means of EDC and HOAt to yield dipeptide amide (XIV). A further treatment of (XIV) with trifluoroacetic acid removed the Boc protecting group to yield (XV), which was then coupled with amino acid (VII) in the presence of EDC and HOAt yielding (XVI). Finally, deprotection of the Boc-tripeptide (XVI) with trifluoroacetic acid provided the title compound.

参考文献中间体

合成目标

【1】 Hansen, T.K.; Ankersen, M.; Hansen, B.S.; Raun, K.; Nielsen, K.K.; Lau, J.; Peschke, B.; Lundt, B.F.; Thogersen, H.; Johansen, N.L.; Madsen, K.; Andersen, P.H.; Novel orally active growth hormone secretagogues. J Med Chem 1998, 41, 19, 3705.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	22191	(E)-5-[(tert-butoxycarbonyl)amino]-5-methyl-2-hexenoic acid		C₁₂H₂₁NO₄	详情	详情
(VIII)	22184	(2R)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropionic acid		C₁₄H₁₉NO₄	详情	详情
(IX)	22185	(2R)-2-[(tert-butoxycarbonyl)(methyl)amino]-3-phenylpropionic acid	37553-65-4	C₁₅H₂₁NO₄	详情	详情
(X)	27231	tert-butyl (1R)-1-benzyl-2-(methylamino)-2-oxoethyl(methyl)carbamate		C₁₆H₂₄N₂O₃	详情	详情
(XI)	27232	(2R)-N-methyl-2-(methylamino)-3-phenylpropanamide		C₁₁H₁₆N₂O	详情	详情
(XII)	23498	(2R)-2-[(tert-butoxycarbonyl)amino]-3-(2-naphthyl)propionic acid		C₁₈H₂₁NO₄	详情	详情
(XIII)	22189	(2R)-2-[(tert-butoxycarbonyl)(methyl)amino]-3-(2-naphthyl)propionic acid	147577-61-5	C₁₉H₂₃NO₄	详情	详情
(XIV)	27233	tert-butyl (1R)-2-[[(1R)-1-benzyl-2-(methylamino)-2-oxoethyl](methyl)amino]-1-(2-naphthylmethyl)-2-oxoethyl(methyl)carbamate		C₃₀H₃₇N₃O₄	详情	详情
(XV)	27234	(2R)-N-[(1R)-1-benzyl-2-(methylamino)-2-oxoethyl]-N-methyl-2-(methylamino)-3-(2-naphthyl)propanamide		C₂₅H₂₉N₃O₂	详情	详情
(XVI)	27235	tert-butyl (E)-5-[[(1R)-2-[[(1R)-1-benzyl-2-(methylamino)-2-oxoethyl](methyl)amino]-1-(2-naphthylmethyl)-2-oxoethyl](methyl)amino]-1,1-dimethyl-5-oxo-3-pentenylcarbamate		C₃₇H₄₈N₄O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIII)

The condensation of N-Boc-N-methyl-D-phenylalanine (VIII) with methylamine by means of EDC and HOBt gave the corresponding amide (IX). After acid deprotection of the Boc group of (IX), the resulting amino compound (X) was coupled with N-Boc-N-methyl-D-naphthylalanine (XI) using EDC and HOAt to provide dipeptide (XII). The Boc protecting group of (XII) was further cleaved with trifluoroacetic acid to give (XIII).

参考文献中间体

合成目标

【1】 Hansen, T.K.; Peschke, B.; Lau, J.; Lundt, B.F.; Ankersen, M.; Watson, B.; Madsen, K. (Novo Nordisk A/S); Cpds. with growth hormone releasing properties. JP 1999209336; JP 1999501054; JP 2000143613; US 6127391; WO 9723508 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	11021	Methanamine; Methylamine	74-89-5	CH₅N	详情	详情
(VIII)	22185	(2R)-2-[(tert-butoxycarbonyl)(methyl)amino]-3-phenylpropionic acid	37553-65-4	C₁₅H₂₁NO₄	详情	详情
(IX)	27231	tert-butyl (1R)-1-benzyl-2-(methylamino)-2-oxoethyl(methyl)carbamate		C₁₆H₂₄N₂O₃	详情	详情
(X)	27232	(2R)-N-methyl-2-(methylamino)-3-phenylpropanamide		C₁₁H₁₆N₂O	详情	详情
(XI)	22189	(2R)-2-[(tert-butoxycarbonyl)(methyl)amino]-3-(2-naphthyl)propionic acid	147577-61-5	C₁₉H₂₃NO₄	详情	详情
(XII)	27233	tert-butyl (1R)-2-[[(1R)-1-benzyl-2-(methylamino)-2-oxoethyl](methyl)amino]-1-(2-naphthylmethyl)-2-oxoethyl(methyl)carbamate		C₃₀H₃₇N₃O₄	详情	详情
(XIII)	27234	(2R)-N-[(1R)-1-benzyl-2-(methylamino)-2-oxoethyl]-N-methyl-2-(methylamino)-3-(2-naphthyl)propanamide		C₂₅H₂₉N₃O₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XIII)

Coupling of amino acid (VII) with dipeptide (XIII) employing EDC and HOAt yielded tripeptide (XIV). The Boc group of (XIV) was then deprotected with trifluoroacetic acid to furnish the title compound.

参考文献中间体

合成目标

【1】 Madsen, K.; Kruse hansen, T.; Watson, B.; Peschke, B.; Langeland Johansen, N.; Sehested Hansen, B.; Lau, J.; Thogersen, H.; Ankersen, M.; Petersen, H.; Synthesis and in vitro characterization of new growth hormone secretagogues derived form ipamorelin with dipeptidomimetic N-terminals. Eur J Med Chem 1999, 34, 5, 363.
【2】 Hansen, T.K.; Peschke, B.; Lau, J.; Lundt, B.F.; Ankersen, M.; Watson, B.; Madsen, K. (Novo Nordisk A/S); Cpds. with growth hormone releasing properties. JP 1999209336; JP 1999501054; JP 2000143613; US 6127391; WO 9723508 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VII)	37820	(E)-5-[(tert-butoxycarbonyl)(methyl)amino]-5-methyl-2-hexenoic acid	C₁₃H₂₃NO₄	详情	详情
(XIII)	27234	(2R)-N-[(1R)-1-benzyl-2-(methylamino)-2-oxoethyl]-N-methyl-2-(methylamino)-3-(2-naphthyl)propanamide	C₂₅H₂₉N₃O₂	详情	详情
(XIV)	27821	(E)-3-(4-hydroxyphenyl)-2-propenamide	C₉H₉NO₂	详情	详情

Extended Information