tert-butyl (2S)-4-methyl-2-(methylamino)pentanoate -Drug Synthesis Database

【结构式】

【分子编号】26296

【品名】tert-butyl (2S)-4-methyl-2-(methylamino)pentanoate

【CA登记号】

【分子式】C₁₁H₂₃NO₂

【分子量】201.30916

【元素组成】C 65.63% H 11.52% N 6.96% O 15.9%

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：(XXXV)

Treatment of N-Boc-N-methyl-L-leucine (XXXIV) with isobutene and H2SO4 in CH2Cl2 generated tert-butyl ester (XXXV) with simultaneous removal of the Boc group. Subsequent coupling of (XXXV) with N-Boc-5-propyl-L-leucine (X) utilizing EDC and HOAt provided dipeptide (XXXVI). Selective removal of the N-Boc group of (XXXVI) was accomplished by treatment with formic acid at r.t. The resulting amine (XXXVII) was then coupled with hydroxyacid (XXXIII) to yield the target tripeptide (XXXVIII).

参考文献中间体

合成目标

【1】 Boger, D.L.; et al.; Total synthesis of HUN-7293. J Am Chem Soc 1999, 121, 26, 6197.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	26272	(2S,4R)-2-[(tert-butoxycarbonyl)amino]-4-methyloctanoic acid		C₁₄H₂₇NO₄	详情	详情
(XXXIII)	26294	(2S)-4-cyano-2-hydroxybutyric acid		C₅H₇NO₃	详情	详情
(XXXIV)	26295	(2S)-2-[(tert-butoxycarbonyl)(methyl)amino]-4-methylpentanoic acid	609-23-4	C₁₂H₂₃NO₄	详情	详情
(XXXV)	26296	tert-butyl (2S)-4-methyl-2-(methylamino)pentanoate		C₁₁H₂₃NO₂	详情	详情
(XXXVI)	26297	tert-butyl (2S)-2-[[(2S,4R)-2-[(tert-butoxycarbonyl)amino]-4-methyloctanoyl](methyl)amino]-4-methylpentanoate		C₂₅H₄₈N₂O₅	详情	详情
(XXXVII)	26298	tert-butyl (2S)-2-[[(2S,4R)-2-amino-4-methyloctanoyl](methyl)amino]-4-methylpentanoate		C₂₀H₄₀N₂O₃	详情	详情
(XXXVIII)	26299	tert-butyl (2S)-2-[((2S,4R)-2-[[(2S)-4-cyano-2-hydroxybutanoyl]amino]-4-methyloctanoyl)(methyl)amino]-4-methylpentanoate		C₂₅H₄₅N₃O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

N-Methyl-L-leucine (IV) was converted to tert-butyl ester (V) by treatment with isobutylene and H2SO4. Formation of the N,N-dialkyl derivative (VIII) was achieved by either alkylation of (V) with p-tert-butylbenzyl bromide (VI) or by reductive condensation of (V) with p-tert-butylbenzaldehyde (VII) and NaBH(OAc)3. Deprotection of the tert-butyl ester of (VIII) with trifluoroacetic acid gave amino acid (IX), which was activated as the mixed anhydride (X) upon treatment with isobutyl chloroformate and a polymer-supported morpholine base. Coupling of (X) with tyrosine amide (III) then afforded the title dipeptide amide. Unreacted starting materials were captured by the addition of polymer-supported polyamine and isocyanate resins.

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
(III)	30798	(2S)-2-amino-3-[4-(benzyloxy)phenyl]-N-(tert-butyl)propanamide		C₂₀H₂₆N₂O₂	详情	详情
(IV)	34642	(2S)-4-methyl-2-(methylamino)pentanoic acid		C₇H₁₅NO₂	详情	详情
(V)	26296	tert-butyl (2S)-4-methyl-2-(methylamino)pentanoate		C₁₁H₂₃NO₂	详情	详情
(VI)	20588	1-(bromomethyl)-4-(tert-butyl)benzene	18880-00-7	C₁₁H₁₅Br	详情	详情
(VII)	16638	4-(tert-butyl)benzaldehyde; 4-tert-Butyl-benzaldehyde	939-97-9	C₁₁H₁₄O	详情	详情
(VIII)	34643	tert-butyl (2S)-2-[[4-(tert-butyl)benzyl](methyl)amino]-4-methylpentanoate		C₂₂H₃₇NO₂	详情	详情
(IX)	34644	(2S)-2-[[4-(tert-butyl)benzyl](methyl)amino]-4-methylpentanoic acid		C₁₈H₂₉NO₂	详情	详情
(X)	34645			C₂₃H₃₇NO₄	详情	详情

Extended Information