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【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

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).

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.

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
(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.

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 CAS号 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