tert-butyl 3-(4-amino-3-propionylphenoxy)propylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】49954

【品名】tert-butyl 3-(4-amino-3-propionylphenoxy)propylcarbamate

【CA登记号】

【分子式】C₁₇H₂₆N₂O₄

【分子量】322.40452

【元素组成】C 63.33% H 8.13% N 8.69% O 19.85%

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：(XXVII)

The precursor aminopropiophenone (XXVII) was synthesized as follows: 3-Amino-1-propanol (XX) was converted to the N-Boc derivative (XXI) and subsequently sulfonylated with p-toluenesulfonyl chloride to afford tosylate (XXII). Addition of vinylmagnesium bromide to 5-hydroxy-2-nitrobenzaldehyde (XXIII) provided the allyl alcohol (XXIV). The phenolic hydroxyl of (XXIV) was then alkylated with tosylate (XXII), yielding ether (XXV). The oxidation of the OH group of (XXV) with MnO2 gave the unsaturated ketone (XXVI). Catalytic hydrogenation of the olefin and nitro groups of (XXVI) provided the aminopropiophenone (XXVII).

参考文献中间体

合成目标

【1】 Tsujihara, K.; Kawaguchi, T.; Okuno, S.; Yano, T. (Tanabe Seiyaku Co., Ltd.); Camptothecin derivs.. CA 2182244; EP 0757049; JP 1998072467; US 5837673 .
【2】 Nomura, S.; Tsujihara, K.; Kawaguchi, T. (Tanabe Seiyaku Co., Ltd.); S type 2-substd. hydroxy-2-indolidinylbutyric ester cpds. and process for preparation thereof. US 6277992 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XX)	18522	3-amino-1-propanol	156-87-6	C₃H₉NO	详情	详情
(XXI)	10260	tert-butyl N-(3-hydroxypropyl)carbamate	58885-58-8	C₈H₁₇NO₃	详情	详情
(XXII)	49950	3-[(tert-butoxycarbonyl)amino]propyl 4-methylbenzenesulfonate		C₁₅H₂₃NO₅S	详情	详情
(XXIII)	14942	5-hydroxy-2-nitrobenzaldehyde	42454-06-8	C₇H₅NO₄	详情	详情
(XXIV)	49951	3-(1-hydroxy-2-propenyl)-4-nitrophenol		C₉H₉NO₄	详情	详情
(XXV)	49952	tert-butyl 3-[3-(1-hydroxy-2-propenyl)-4-nitrophenoxy]propylcarbamate		C₁₇H₂₄N₂O₆	详情	详情
(XXVI)	49953	tert-butyl 3-(3-acryloyl-4-nitrophenoxy)propylcarbamate		C₁₇H₂₂N₂O₆	详情	详情
(XXVII)	49954	tert-butyl 3-(4-amino-3-propionylphenoxy)propylcarbamate		C₁₇H₂₆N₂O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXVII)

The title compound was prepared from aminopropiophenone (XXVII) by several procedures. Aldol condensation of (XXVII) with the intermediate pyranoindolizinetrione (XVII) with concomitant Friedlander quinoline synthesis under acidic conditions furnished the camptothecin derivative (XXVIII). Optionally, (XXVIII) was also obtained by condensation of (XXVII) with intermediate ketone (XIX), followed by basic hydrolysis of the resultant lactone-ester (XXIX) and subsequent relactonization under acidic conditions. Finally, acid cleavage of the N-Boc group of (XXVII) yielded the title compound.

参考文献中间体

合成目标

【1】 Tsujihara, K.; Kawaguchi, T.; Okuno, S.; Yano, T. (Tanabe Seiyaku Co., Ltd.); Camptothecin derivs.. CA 2182244; EP 0757049; JP 1998072467; US 5837673 .
【2】 Nomura, S.; Tsujihara, K.; Kawaguchi, T. (Tanabe Seiyaku Co., Ltd.); S type 2-substd. hydroxy-2-indolidinylbutyric ester cpds. and process for preparation thereof. US 6277992 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XVII)	10841	(4S)-4-Ethyl-4-hydroxy-7,8-dihydro-1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione	C₁₃H₁₃NO₅	详情	详情
(XIX)	49949	(4S)-4-ethyl-3,6,10-trioxo-3,4,6,7,8,10-hexahydro-1H-pyrano[3,4-f]indolizin-4-yl acetate	C₁₅H₁₅NO₆	详情	详情
(XXVII)	49954	tert-butyl 3-(4-amino-3-propionylphenoxy)propylcarbamate	C₁₇H₂₆N₂O₄	详情	详情
(XXVIII)	49955	tert-butyl 3-[[(4S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl]oxy]propylcarbamate	C₃₀H₃₅N₃O₇	详情	详情
(XXIX)	49956	(4S)-9-[3-[(tert-butoxycarbonyl)amino]propoxy]-4,11-diethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4-yl acetate	C₃₂H₃₇N₃O₈	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XXVII)

In an alternative procedure, condensation of aminopropiophenone (XXVII) with the intermediate pyranoindolizinetrione (XIV) under acidic conditions gave rise to camptothecin derivative (XXX). Basic hydrolysis of the chiral auxiliary ester and lactone groups of (XXX) followed by acidic relactonization then gave the precursor (XXVIII), which was finally subjected to Boc group cleavage as indicated above.

参考文献中间体

合成目标

【1】 Nomura, S.; Tsujihara, K.; Kawaguchi, T. (Tanabe Seiyaku Co., Ltd.); S type 2-substd. hydroxy-2-indolidinylbutyric ester cpds. and process for preparation thereof. US 6277992 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XIV)	49945	(4S)-4-ethyl-3,6,10-trioxo-3,4,6,7,8,10-hexahydro-1H-pyrano[3,4-f]indolizin-4-yl (3R)-2-([1,1'-biphenyl]-4-ylsulfonyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylate	C₃₅H₃₀N₂O₈S	详情	详情
(XXVII)	49954	tert-butyl 3-(4-amino-3-propionylphenoxy)propylcarbamate	C₁₇H₂₆N₂O₄	详情	详情
(XXVIII)	49955	tert-butyl 3-[[(4S)-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl]oxy]propylcarbamate	C₃₀H₃₅N₃O₇	详情	详情
(XXX)	49957	(4S)-9-[3-[(tert-butoxycarbonyl)amino]propoxy]-4,11-diethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4-yl (3R)-2-([1,1'-biphenyl]-4-ylsulfonyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylate	C₅₂H₅₂N₄O₁₀S	详情	详情

Extended Information