(2S)-2-amino-3-(1,3-benzothiazol-2-yl)-1-[4-(2-fluoroethyl)-1-piperidinyl]-1-propanone -Drug Synthesis Database

【结构式】

【分子编号】43465

【品名】(2S)-2-amino-3-(1,3-benzothiazol-2-yl)-1-[4-(2-fluoroethyl)-1-piperidinyl]-1-propanone

【CA登记号】

【分子式】C₁₇H₂₂FN₃OS

【分子量】335.4457032

【元素组成】C 60.87% H 6.61% F 5.66% N 12.53% O 4.77% S 9.56%

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：(XIV)

Amine intermediate (XIV) has been obtained as follows: N-(Carbobenzoxy)-L-aspartic acid alpha-benzyl ester (VII) was converted to acid chloride (VIII) and then coupled to 2-aminophenyl disulfide (IX) to afford the bis-amide (X). Reductive cleavage of the disulfide group of (X), followed by basic cyclization, produced the benzothiazole (XI) (2). Hydrolysis of the benzyl ester group of (XI) and subsequent coupling of the resulting carboxylic acid (XII) with piperidine (VI) gave amide (XIII). The carbobenzoxy group of (XII) was then cleaved with HBr in HOAc, yielding intermediate amine (XIV).

参考文献中间体

合成目标

【1】 Baettig, U.; et al.; The design and synthesis of thrombin inhibitors: Analogues of MD805 containing non-polar surrogates for arginine at the P1 position. Bioorg Med Chem Lett 2000, 10, 14, 1563.
【2】 Smith, G.P.; Brundish, D.E.; Menear, K.A.; Walker, C.V.; Herold, P.; Fullerton, J.D.; Allen, M.C.; Le Grand, D.M.; Kane, P.D.; Cockcroft, X.-L.; Wathey, W.B.; Butler, P.I.; Hatto, J.D.I.; Hayler, J.D. (Novartis AG); Tetrahydroquinoline inhibitors of trypsin and thrombin. GB 2312674 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	28517	4-(2-fluoroethyl)piperidine		C₇H₁₄FN	详情	详情
(VII)	43458	(3S)-4-(benzyloxy)-3-[[(benzyloxy)carbonyl]amino]-4-oxobutyric acid	4779-31-1	C₁₉H₁₉NO₆	详情	详情
(VIII)	43459	benzyl (2S)-2-[[(benzyloxy)carbonyl]amino]-4-chloro-4-oxobutanoate		C₁₉H₁₈ClNO₅	详情	详情
(IX)	43460	2-[(2-aminophenyl)disulfanyl]aniline; 2-[(2-aminophenyl)disulfanyl]phenylamine	1141-88-4	C₁₂H₁₂N₂S₂	详情	详情
(X)	43461	benzyl (2S)-4-[2-([2-[((3S)-4-(benzyloxy)-3-[[(benzyloxy)carbonyl]amino]-4-oxobutanoyl)amino]phenyl]disulfanyl)anilino]-2-[[(benzyloxy)carbonyl]amino]-4-oxobutanoate		C₅₀H₄₆N₄O₁₀S₂	详情	详情
(XI)	43462	benzyl (2S)-3-(1,3-benzothiazol-2-yl)-2-[[(benzyloxy)carbonyl]amino]propanoate		C₂₅H₂₂N₂O₄S	详情	详情
(XII)	43463	(2S)-3-(1,3-benzothiazol-2-yl)-2-[[(benzyloxy)carbonyl]amino]propionic acid		C₁₈H₁₆N₂O₄S	详情	详情
(XIII)	43464	benzyl (1S)-1-(1,3-benzothiazol-2-ylmethyl)-2-[4-(2-fluoroethyl)-1-piperidinyl]-2-oxoethylcarbamate		C₂₅H₂₈FN₃O₃S	详情	详情
(XIV)	43465	(2S)-2-amino-3-(1,3-benzothiazol-2-yl)-1-[4-(2-fluoroethyl)-1-piperidinyl]-1-propanone		C₁₇H₂₂FN₃OS	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIV)

Coupling between sulfonyl chloride (XXIV) and amine (XIV) provided sulfonamide (XXXIV). The ethyl ester group of (XXXIV) was then hydrolyzed to carboxylic acid (XXXV), which was finally coupled with N-(2-morpholin-4-yl-2-oxoethyl)piperazine (XXXVI) to furnish the title amide.

参考文献中间体

合成目标

【1】 Hayler, J.; LeGrand, D.; Kane, P.D.; et al.; The design and synthesis of thrombin inhibitors: The introduction of in vivo efficacy and oral bioavailability into benzthiazolylalanine inhibitors. Bioorg Med Chem Lett 2000, 10, 14, 1567.
【2】 Smith, G.P.; Brundish, D.E.; Menear, K.A.; Walker, C.V.; Herold, P.; Fullerton, J.D.; Allen, M.C.; Le Grand, D.M.; Kane, P.D.; Cockcroft, X.-L.; Wathey, W.B.; Butler, P.I.; Hatto, J.D.I.; Hayler, J.D. (Novartis AG); Tetrahydroquinoline inhibitors of trypsin and thrombin. GB 2312674 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XIV)	43465	(2S)-2-amino-3-(1,3-benzothiazol-2-yl)-1-[4-(2-fluoroethyl)-1-piperidinyl]-1-propanone	C₁₇H₂₂FN₃OS	详情	详情
(XXIV)	43472	ethyl 3-[8-(chlorosulfonyl)-3,3-dimethyl-1,2,3,4-tetrahydro-6-quinolinyl]propanoate	C₁₆H₂₂ClNO₄S	详情	详情
(XXXIV)	43482	ethyl 3-[8-[([(1S)-1-(1,3-benzothiazol-2-ylmethyl)-2-[4-(2-fluoroethyl)-1-piperidinyl]-2-oxoethyl]amino)sulfonyl]-3,3-dimethyl-1,2,3,4-tetrahydro-6-quinolinyl]propanoate	C₃₃H₄₃FN₄O₅S₂	详情	详情
(XXXV)	43483	3-[8-[([(1S)-1-(1,3-benzothiazol-2-ylmethyl)-2-[4-(2-fluoroethyl)-1-piperidinyl]-2-oxoethyl]amino)sulfonyl]-3,3-dimethyl-1,2,3,4-tetrahydro-6-quinolinyl]propionic acid	C₃₁H₃₉FN₄O₅S₂	详情	详情
(XXXVI)	43484	1-(4-morpholinyl)-2-(1-piperazinyl)-1-ethanone	C₁₀H₁₉N₃O₂	详情	详情

Extended Information