tert-butyl 2-[(3S)-3-amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl]acetate -Drug Synthesis Database

【结构式】

【分子编号】20717

【品名】tert-butyl 2-[(3S)-3-amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl]acetate

【CA登记号】

【分子式】C₁₆H₂₂N₂O₃

【分子量】290.36236

【元素组成】C 66.18% H 7.64% N 9.65% O 16.53%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(I)

1) The acylation of the chiral amine (I) with the chiral cyclopentanecarboxylic aid (II) by means of N-methylmorphline (NMM), hydroxybenzotriazole (HOBT) and N-(dimethylaminopropyl)-N'-ethylcarbodiimide (EDT) in dichloromethane gives the amide (III), which is then treated with trifluoroacetic acid to elimnate the tert-butyl ester groups.

参考文献中间体

合成目标

【1】 Waldeck, H.; Höltje, D.; Messinger, J.; Antel, J.; Wurl, M.; Thormählen, D. (Kali-Chemie AG); Benzazepin-, benzoxazepin- and benzothiazepin-N-acetic acid-derivs., their preparation and their pharmaceutical compsns.. CA 2172354; EP 0733642; JP 1996269011; US 5677297 .
【2】 Rozsa, S.; Gy Papp, J.; Thormahlen, D.; Waldeck, H. (Solvay SA); Drugs for increasing gastrointestinal blood supply. DE 19638020; EP 0830863; JP 1998101565 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	20717	tert-butyl 2-[(3S)-3-amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl]acetate	C₁₆H₂₂N₂O₃	详情	详情
(II)	20737	1-[(2R)-2-(tert-butoxycarbonyl)-4-phenylbutyl]cyclopentanecarboxylic acid	C₂₁H₃₀O₄	详情	详情
(III)	20738	tert-butyl (2R)-2-([1-[([(3S)-1-[2-(tert-butoxy)-2-oxoethyl]-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino)carbonyl]cyclopentyl]methyl)-4-phenylbutanoate	C₃₇H₅₀N₂O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

2) The chiral intermediates the amine (I) and the acid (II) have been obtained as follows: 2a) The bromination of 1-tetralone (IV) with Br2 in methanol gives the 2-bromotetralone (V), which is treated with hydroxylamine yielding the corresponding oximae (VI). The isomerization of (V) with polyphosphoric acid (PPA) at 80 C affords the benzazepinone (VII), which is treated with potassium phthalimide (VIII) in DMF to give the corresponding phthalimido derivative (IX). The reaction of (IX) with tert-butyl bromoacetate (X) by means of potassium tert-butoxide in DMF yields the benzazepinoacetic ester (XI), which is treated with hot ethanolamine to eliminate the phthalimido group yielding racemic (I). Finally, this racemate is submitted to optical resolution with L-(+)-tartaric acid to afford the chiral (S)-intermediate (I).

参考文献中间体

合成目标

【1】 Waldeck, H.; Höltje, D.; Messinger, J.; Antel, J.; Wurl, M.; Thormählen, D. (Kali-Chemie AG); Benzazepin-, benzoxazepin- and benzothiazepin-N-acetic acid-derivs., their preparation and their pharmaceutical compsns.. CA 2172354; EP 0733642; JP 1996269011; US 5677297 .
【2】 Rozsa, S.; Gy Papp, J.; Thormahlen, D.; Waldeck, H. (Solvay SA); Drugs for increasing gastrointestinal blood supply. DE 19638020; EP 0830863; JP 1998101565 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
rac-(I)	20728	tert-butyl 2-(3-amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)acetate		C₁₆H₂₂N₂O₃	详情	详情
(I)	20717	tert-butyl 2-[(3S)-3-amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl]acetate		C₁₆H₂₂N₂O₃	详情	详情
(IV)	20720	3,4-dihydro-1(2H)-naphthalenone	529-34-0	C₁₀H₁₀O	详情	详情
(V)	20721	2-bromo-3,4-dihydro-1(2H)-naphthalenone		C₁₀H₉BrO	详情	详情
(VI)	20722	2-bromo-3,4-dihydro-1(2H)-naphthalenone oxime		C₁₀H₁₀BrNO	详情	详情
(VII)	20723	3-bromo-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one		C₁₀H₁₀BrNO	详情	详情
(VIII)	10926	(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)potassium		C₈H₄KNO₂	详情	详情
(IX)	20725	2-(2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl)-1H-isoindole-1,3(2H)-dione		C₁₈H₁₄N₂O₃	详情	详情
(X)	17430	2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate	5292-43-3	C₆H₁₁BrO₂	详情	详情
(XI)	20727	tert-butyl 2-[3-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl]acetate		C₂₅H₂₆N₂O₅	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Leeson, P.A.; Castañer, J.; SLV-306. Drugs Fut 2002, 27, 1, 27.
【2】 Waldeck, H.; Höltje, D.; Messinger, J.; Antel, J.; Wurl, M.; Thormählen, D. (Kali-Chemie AG); Benzazepin-, benzoxazepin- and benzothiazepin-N-acetic acid-derivs., their preparation and their pharmaceutical compsns.. CA 2172354; EP 0733642; JP 1996269011; US 5677297 .
【3】 Rozsa, S.; Gy Papp, J.; Thormahlen, D.; Waldeck, H. (Solvay SA); Drugs for increasing gastrointestinal blood supply. DE 19638020; EP 0830863; JP 1998101565 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	20717	tert-butyl 2-[(3S)-3-amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl]acetate	C₁₆H₂₂N₂O₃	详情	详情
(II)	20718	1-[(2R)-2-(ethoxycarbonyl)-4-phenylbutyl]cyclopentanecarboxylic acid	C₁₉H₂₆O₄	详情	详情
(III)	20719	ethyl (2R)-2-([1-[([(3S)-1-[2-(tert-butoxy)-2-oxoethyl]-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl]amino)carbonyl]cyclopentyl]methyl)-4-phenylbutanoate	C₃₅H₄₆N₂O₆	详情	详情

合成路线4

该中间体在本合成路线中的序号：(I)

2a) The chiral intermediate amine (I) has been obtained as follows: The bromination of 1-tetralone (IV) with Br2 in methanol gives the 2-bromotetralone (V), which is treated with hydroxylamine yielding the corresponding oximae (VI). The isomerization of (V) with polyphosphoric acid (PPA) at 80 C affords the benzazepinone (VII), which is treated with potassium phthalimide (VIII) in DMF to give the corresponding phthalimido derivative (IX). The reaction of (IX) with tert-butyl bromoacetate (X) by means of potassium tert-butoxide in DMF yields the benzazepinoacetic ester (XI), which is treated with hot ethanolamine to eliminate the phthalimido group yielding racemic (I). Finally, this racemate is submitted to optical resolution with L-(+)-tartaric acid to afford the chiral (S)-intermediate (I).

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Leeson, P.A.; Castañer, J.; SLV-306. Drugs Fut 2002, 27, 1, 27.
【2】 Waldeck, H.; Höltje, D.; Messinger, J.; Antel, J.; Wurl, M.; Thormählen, D. (Kali-Chemie AG); Benzazepin-, benzoxazepin- and benzothiazepin-N-acetic acid-derivs., their preparation and their pharmaceutical compsns.. CA 2172354; EP 0733642; JP 1996269011; US 5677297 .
【3】 Rozsa, S.; Gy Papp, J.; Thormahlen, D.; Waldeck, H. (Solvay SA); Drugs for increasing gastrointestinal blood supply. DE 19638020; EP 0830863; JP 1998101565 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
rac-(I)	20728	tert-butyl 2-(3-amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)acetate		C₁₆H₂₂N₂O₃	详情	详情
(I)	20717	tert-butyl 2-[(3S)-3-amino-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl]acetate		C₁₆H₂₂N₂O₃	详情	详情
(IV)	20720	3,4-dihydro-1(2H)-naphthalenone	529-34-0	C₁₀H₁₀O	详情	详情
(V)	20721	2-bromo-3,4-dihydro-1(2H)-naphthalenone		C₁₀H₉BrO	详情	详情
(VI)	20722	2-bromo-3,4-dihydro-1(2H)-naphthalenone oxime		C₁₀H₁₀BrNO	详情	详情
(VII)	20723	3-bromo-1,3,4,5-tetrahydro-2H-1-benzazepin-2-one		C₁₀H₁₀BrNO	详情	详情
(VIII)	10926	(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)potassium		C₈H₄KNO₂	详情	详情
(IX)	20725	2-(2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-3-yl)-1H-isoindole-1,3(2H)-dione		C₁₈H₁₄N₂O₃	详情	详情
(X)	17430	2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate	5292-43-3	C₆H₁₁BrO₂	详情	详情
(XI)	20727	tert-butyl 2-[3-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl]acetate		C₂₅H₂₆N₂O₅	详情	详情

Extended Information