(2R)-2-pyrrolidinecarboxamide -Drug Synthesis Database

【结构式】

【分子编号】37077

【品名】(2R)-2-pyrrolidinecarboxamide

【CA登记号】

【分子式】C₅H₁₀N₂O

【分子量】114.14728

【元素组成】C 52.61% H 8.83% N 24.54% O 14.02%

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：(II)

The reduction of N-benzyloxycarbonylprolinamide (I) with H2 over Pd/c in methanol gives prolinamide (II), which is condensed with N-benzyloxycarbonylhistidyl hydrazide (III) by means of NaNO2 - HCl in ethyl acetate yielding N-benzyloxycarbonylhistidylprolinamide (IV), The hydrolysis of (IV) with HBr in acetic acid affords histidylprolinamide (V), which is finally condensed with gamma-carboxy-gamma-butyrolactone (VI) by means of pentachlorophenol and dicyclohexylcarbodiimide in DMF. Compound (VI) is prepared by reaction of alpha-aminoglutaric acid (VII) with NaNO2 and 2N H2SO4 in water.

参考文献中间体

合成目标

【1】 Fujino, M.; Nishimura, P.; Nagawa, Y.; Fukuda, N.; US 4100152 .
【2】 Bauce, L.G.; Goren, H.J.; Synthesis of a series of residue 1-(pyroglutamic acid) analogs of thyrotropin releasing hormone. Intl J Pept Protein Res 1979, 14, 3, 216-226.
【3】 Larsen, S.D.; Stephenson, G.A.; Bunnell, C.A.; Reutzel, S.M.; Nichols, J.R. (Eli Lilly and Company); Intermediates and process for preparing olanzapine. US 6020487 .

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)	37076	benzyl (2R)-2-(aminocarbonyl)-1-pyrrolidinecarboxylate		C₁₃H₁₆N₂O₃	详情	详情
(II)	37077	(2R)-2-pyrrolidinecarboxamide		C₅H₁₀N₂O	详情	详情
(III)	36138	benzyl (1S)-2-hydrazino-1-(1H-imidazol-5-ylmethyl)-2-oxoethylcarbamate	49706-31-2	C₁₄H₁₇N₅O₃	详情	详情
(IV)	36139	benzyl (1S)-2-[(2S)-2-(aminocarbonyl)pyrrolidinyl]-1-(1H-imidazol-5-ylmethyl)-2-oxoethylcarbamate		C₁₉H₂₃N₅O₄	详情	详情
(V)	31253	(2S)-1-[(2S)-2-amino-3-(1H-imidazol-5-yl)propanoyl]-2-pyrrolidinecarboxamide		C₁₁H₁₇N₅O₂	详情	详情
(VI)	37075	5-oxotetrahydro-2-furancarboxylic acid		C₅H₆O₄	详情	详情
(VII)	28752	DL-2-Amino propane dicarboxylic acid; DL-2-Aminopentanoic acid; glutamic acid; DL-glutamic acid; (+/-)-2-Aminoglutaric acid	617-65-2	C₅H₉NO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The title compound was prepared by solid-phase peptide synthesis starting from N-Fmoc-D-proline linked to Rink resin (I). Deprotection of the Fmoc group by means of piperidine in DMA afforded proline-resin (II). Coupling of N-alpha-Fmoc-NG-Pmc-D-arginine (III) to proline-resin (II) using diisopropyl carbodiimide (DIC) and HOBt, followed by Fmoc deprotection with piperidine in DMA, furnished dipeptide-resin (IV). Further coupling and deprotection cycles incorporating the amino acid N2-Fmoc-N6-Boc-D-lysine (V) (twice) and the peptoid residue N-Fmoc-N-[3-(3-Pmc-guanidino)propyl]glycine (VIII) yielded the peptide resins (VI), (VII) and (IX), respectively.

参考文献中间体

合成目标

【1】 Hamy, F.; et al.; An inhibitor of the Tat/TAR RNA interaction that effectively suppresses HIV-1 replication. Proceedings of the National Academy of Sciences of the United States of America 1997, 94, 8, 3548.
【2】 Felder, E.; Hamy, F.; Heizmann, G.; Klimkait, T.; Lazdins, J.K. (Novartis AG); Antiviral peptoid cpds.. EP 0832110; WO 9640759 .

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)	42841	9H-fluoren-9-ylmethyl (2R)-2-(aminocarbonyl)-1-pyrrolidinecarboxylate		C₂₀H₂₀N₂O₃	详情	详情
(II)	37077	(2R)-2-pyrrolidinecarboxamide		C₅H₁₀N₂O	详情	详情
(III)	19035	(2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-5-[(imino[[(2,2,5,7,8-pentamethyl-3,4-dihydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]pentanoic acid	119831-72-0	C₃₅H₄₂N₄O₇S	详情	详情
(IV)	42842	(2R)-1-[(2R)-2-amino-5-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]pentanoyl]-2-pyrrolidinecarboxamide		C₂₅H₄₂N₆O₅S	详情	详情
(V)	42847	(2R)-6-[(tert-butoxycarbonyl)amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]hexanoic acid		C₂₆H₃₂N₂O₆	详情	详情
(VI)	42843	tert-butyl (5R)-5-amino-6-([(1R)-1-[[(2R)-2-(aminocarbonyl)pyrrolidinyl]carbonyl]-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyl]amino)-6-oxohexylcarbamate		C₃₆H₆₂N₈O₈S	详情	详情
(VII)	42844	tert-butyl (5R)-5-amino-6-([(1R)-1-[([(1R)-1-[[(2R)-2-(aminocarbonyl)pyrrolidinyl]carbonyl]-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyl]amino)carbonyl]-5-[(tert-butoxycarbonyl)amino]pentyl		C₄₇H₈₂N₁₀O₁₁S	详情	详情
(VIII)	42845	2-([(9H-fluoren-9-ylmethoxy)carbonyl][3-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]propyl]amino)acetic acid		C₃₅H₄₄N₄O₇S	详情	详情
(IX)	42846	tert-butyl (5R,8R)-5-[([(1R)-1-[[(2R)-2-(aminocarbonyl)pyrrolidinyl]carbonyl]-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyl]amino)carbonyl]-8-[4-[(tert-butoxycarbonyl)amino]butyl]-17-imino-7		C₆₇H₁₁₄N₁₄O₁₅S₂	详情	详情

Extended Information