(2S)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-piperidinecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】25357

【品名】(2S)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-piperidinecarboxylic acid

【CA登记号】

【分子式】C₂₁H₂₁NO₄

【分子量】351.40208

【元素组成】C 71.78% H 6.02% N 3.99% O 18.21%

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：(XVIII)

In an alternative procedure, the intermediate alcohol (VIII) was coupled with N-Fmoc-(S)-pipecolic acid (XVIII) using DCC and DMAP to give ester (XIX). Subsequent deprotection of the Fmoc group of (XIX) by means of pyrrolidine provided amine (XX). This was further coupled to racemic 2-(3,4,5-trimethoxyphenyl)butyric acid (X), and the resulting diastereomeric mixture of amides (XXI) was separated by column chromatography. Then, TFA-promoted cleavage of the tert-butyl ester from the desired (S,S)-diastereoisomer provided carboxylic acid (XXII), which was finally coupled to ethylenediamine in the same way as before.

参考文献中间体

合成目标

【1】 Clackson, T.; Yang, W.; Rozamus, L.W.; Hatada, M.; Amara, J.F.; Rollins, C.T.; Stevenson, L.F.; Magari, S.R.; Wood, S.A.; Courage, N.L.; Lu, X.; Cerasoli, F. Jr; Gilman, M.; Holt, D.A.; Redesigning an FKBP-ligand interface to generate chemical dimerizers with novel specificity. Proc Natl Acad Sci USA 1998, 95, 18, 10437.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VIII)	25348	tert-butyl 2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-hydroxypropyl]phenoxy]acetate	C₂₃H₃₀O₆	详情	详情
(X)	25350	2-(3,4,5-trimethoxyphenyl)butyric acid	C₁₃H₁₈O₅	详情	详情
(XVIII)	25357	(2S)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-piperidinecarboxylic acid	C₂₁H₂₁NO₄	详情	详情
(XIX)	25358	2-[(1R)-1-[3-[2-(tert-butoxy)-2-oxoethoxy]phenyl]-3-(3,4-dimethoxyphenyl)propyl] 1-(9H-fluoren-9-ylmethyl) (2S)-1,2-piperidinedicarboxylate	C₄₄H₄₉NO₉	详情	详情
(XX)	25359	(1R)-1-[3-[2-(tert-butoxy)-2-oxoethoxy]phenyl]-3-(3,4-dimethoxyphenyl)propyl (2S)-2-piperidinecarboxylate	C₂₉H₃₉NO₇	详情	详情
(XXI)	25360	(1R)-1-[3-[2-(tert-butoxy)-2-oxoethoxy]phenyl]-3-(3,4-dimethoxyphenyl)propyl (2S)-1-[2-(3,4,5-trimethoxyphenyl)butanoyl]-2-piperidinecarboxylate	C₄₂H₅₅NO₁₁	详情	详情
(XXII)	25361	2-(3-[(1R)-3-(3,4-dimethoxyphenyl)-1-[([(2S)-1-[(2S)-2-(3,4,5-trimethoxyphenyl)butanoyl]piperidinyl]carbonyl)oxy]propyl]phenoxy)acetic acid	C₃₈H₄₇NO₁₁	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

(S)-Pipecolinic acid (I) was protected as the Fmoc-derivative (II) using 9-fluorenylmethyl chloroformate and Na2CO3. Subsequent coupling of (II) with O-(tert-butyldiphenylsilyl)hydroxylamine (III) by means of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) provided the silyl hydroxamate (IV). Removal of the Fmoc group of (IV) was then achieved by treatment with diethylamine in THF to provide (V). Treatment of N-(2-pyridyl)piperazine (VI) with chlorosulfonic acid and then with phosphorus pentachloride afforded the sulfamyl chloride (VII). This was coupled with piperidine (V) in the presence of Et3N to yield the sulfamide derivative (VIII). Finally, removal of the silyl protecting group of (VIII) was carried out with tetrabutylammonium fluoride in CH2Cl2.

参考文献中间体

合成目标

【1】 Mitchell, L.J. Jr.; Burke, B.; Dagostino, E.; et al.; Novel sulfamides and sulfonamide inhibitors of matrix metalloproteases. 218th ACS Natl Meet (Aug 22 1999, New Orleans) 1999, Abst MEDI 76.

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)	17380	(2S)hexahydro-2-pyridinecarboxylic acid; (S)-pipecolic acid	3105-95-1	C₆H₁₁NO₂	详情	详情
(II)	25357	(2S)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-2-piperidinecarboxylic acid		C₂₁H₂₁NO₄	详情	详情
(III)	33013	O-[tert-butyl(diphenyl)silyl]hydroxylamine; (aminooxy)(tert-butyl)diphenylsilane		C₁₆H₂₁NOSi	详情	详情
(IV)	33009	9H-fluoren-9-ylmethyl (2R)-2-[([[tert-butyl(diphenyl)silyl]oxy]amino)carbonyl]-1-piperidinecarboxylate		C₃₇H₄₀N₂O₄Si	详情	详情
(V)	33010	(2R)-N-[[tert-butyl(diphenyl)silyl]oxy]-2-piperidinecarboxamide		C₂₂H₃₀N₂O₂Si	详情	详情
(VI)	24399	1-(2-pyridinyl)piperazine	34803-66-2	C₉H₁₃N₃	详情	详情
(VII)	33011	4-(2-pyridinyl)-1-piperazinesulfonyl chloride		C₉H₁₂ClN₃O₂S	详情	详情
(VIII)	33012	(2R)-N-[[tert-butyl(diphenyl)silyl]oxy]-1-[[4-(2-pyridinyl)-1-piperazinyl]sulfonyl]-2-piperidinecarboxamide		C₃₁H₄₁N₅O₄SSi	详情	详情

Extended Information