tert-butyl (2S)-2-[[methoxy(methyl)amino]carbonyl]-1-pyrrolidinecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】46320

【品名】tert-butyl (2S)-2-[[methoxy(methyl)amino]carbonyl]-1-pyrrolidinecarboxylate

【CA登记号】

【分子式】C₁₂H₂₂N₂O₄

【分子量】258.31776

【元素组成】C 55.8% H 8.58% N 10.84% O 24.77%

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 reaction of N-Boc-L-proline (IX) with O-methylhydroxylamine (II) gives the corresponding amide (X), which is reduced with LiAlH4 to N-Boc-L-prolinal (XI). The condensation of (XI) with boronate (XII) yields the carbinol (XIII) as the greater isomer, and it is methylated with Me-I and NaH to afford the methyl ether (XIV). Finally, the terminal double bond of (XIV) is oxidated by means of RuO4 to furnish the desired intermediate, the amino acid (XV).

参考文献中间体

合成目标

【1】 Roux, F.; et al.; Synthesis of dolastatin-10 and [R-Doe]-dolastatin-10. Tetrahedron 1994, 50, 18, 5345.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	46320	tert-butyl (2S)-2-[[methoxy(methyl)amino]carbonyl]-1-pyrrolidinecarboxylate		C₁₂H₂₂N₂O₄	详情	详情
(IX)	16734	(2S)-1-(tert-butoxycarbonyl)tetrahydro-1H-pyrrole-2-carboxylic acid; N-alpha-t-BOC-L-proline; (2S)-1-(tert-butoxycarbonyl)-2-pyrrolidinecarboxylic acid		C₁₀H₁₇NO₄	详情	详情
(X)	13361	(Methoxyamino)methane; N,O-Dimethylhydroxylamine	1117-97-1	C₂H₇NO	详情	详情
(XI)	16724	tert-Butyl (2S)-2-formyltetrahydro-1H-pyrrole-1-carboxylate; tert-Butoxycarbonyl-L-prolinal	69610-41-9	C₁₀H₁₇NO₃	详情	详情
(XII)	54600	2-[(Z)-2-butenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane		C₁₀H₁₉BO₂	详情	详情
(XIII)	54601	tert-butyl (2S)-2-[(1R,2S)-1-hydroxy-2-methyl-3-butenyl]-1-pyrrolidinecarboxylate		C₁₄H₂₅NO₃	详情	详情
(XIV)	54602	tert-butyl (2S)-2-[(1R,2S)-1-methoxy-2-methyl-3-butenyl]-1-pyrrolidinecarboxylate		C₁₅H₂₇NO₃	详情	详情
(XV)	23520	(2R,3R)-3-[(2S)-1-(tert-butoxycarbonyl)pyrrolidinyl]-3-methoxy-2-methylpropionic acid		C₁₄H₂₅NO₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Condensation of the Weinreb amide of N-Boc-proline (I) with the lithium anion of benzothiazole (II) in THF at -78 C gave benzothiazolyl ketone (III), which was reduced with NaBH4 to afford the diastereomeric mixture of alcohols (IV). Deprotection of the Boc group of (IV) by means of HCl in EtOAc provided pyrrolidine (V). This was then coupled with Z-leucyl-glycine (VI) in the presence of PyBOP to give the peptidyl alcohol (VII). Finally, Swern oxidation of (VII) furnished the corresponding ketone.

参考文献中间体

合成目标

【1】 Santana, J.; Gullet, C.; Schrével, J.; Frappier, F.; Maoulida, C.; Grellier, P.; Joyeau, R.; Teixeira, A.R.L.; Synthesis and activity of pyrrolidinyl- and thiazolidinyl-dipeptide derivatives as inhibitors of the Tc80 prolyl oligopeptidase from Trypanosoma cruzi. Eur J Med Chem 2000, 35, 2, 257.

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)	46320	tert-butyl (2S)-2-[[methoxy(methyl)amino]carbonyl]-1-pyrrolidinecarboxylate		C₁₂H₂₂N₂O₄	详情	详情
(II)	36784	1,3-benzothiazole	95-16-9	C₇H₅NS	详情	详情
(III)	46321	tert-butyl (2S)-2-(1,3-benzothiazol-2-ylcarbonyl)-1-pyrrolidinecarboxylate		C₁₇H₂₀N₂O₃S	详情	详情
(IV)	46322	tert-butyl (2S)-2-[(R)-1,3-benzothiazol-2-yl(hydroxy)methyl]-1-pyrrolidinecarboxylate		C₁₇H₂₂N₂O₃S	详情	详情
(V)	46323	(R)-1,3-benzothiazol-2-yl[(2S)pyrrolidinyl]methanol		C₁₂H₁₄N₂OS	详情	详情
(VI)	46318	2-[((2S)-2-[[(benzyloxy)carbonyl]amino]-4-methylpentanoyl)amino]acetic acid		C₁₆H₂₂N₂O₅	详情	详情
(VII)	46324	benzyl (1S)-1-[[(2-[(2S)-2-[(R)-1,3-benzothiazol-2-yl(hydroxy)methyl]pyrrolidinyl]-2-oxoethyl)amino]carbonyl]-3-methylbutylcarbamate		C₂₈H₃₄N₄O₅S	详情	详情

Extended Information