ethyl 3-(trimethylsilyl)-2-propynoate -Drug Synthesis Database

【结构式】

【分子编号】23898

【品名】ethyl 3-(trimethylsilyl)-2-propynoate

【CA登记号】29394-58-9

【分子式】C₈H₁₄O₂Si

【分子量】170.28346

【元素组成】C 56.43% H 8.29% O 18.79% Si 16.49%

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：(III)

A short and efficient synthesis of xemilofiban has been achieved as follows: The reaction of ethyl chloroformate (I) with trimethylsilylacetylene (II) by means of butyllithium gives ethyl 3-(trimethylsilyl)propyonate (III), which is condensed with the lithium salt of ethyl acetate (IV) yielding ethyl 5-(trimethylsilyl)-3-oxo-4-pentynoate (V). The selective reduction of (V) with lyophilized baker's yeast (Saccharomyces cerevisiae, Sigma type II) affords ethyl 3(R)-hydroxy-5-(trimethylsilyl)-4-pentynoate (VI), which by reaction with ammonia (VII), diethyl azodicarboxylate (VIII) and triphenylphosphine, followed by hydrolysis with water gives 3(S)-amino-5-(trimethylsilyl)-4-pentynoate (IX). Finally, this compound is condensed with N-(4-amidinophenyl)succinamic acid (XI) by means of isobutyl chloroformate and N-methylmorpholine (NMM). The intermediate succinamic acid (XI) has been obtained by condensation of 4-aminobenzamidine (XII) with succinic anhydride (XIII) in DMF.

参考文献中间体

合成目标

【1】 Cossy, J.; Schmitt, A.; Cinquin, C.; Buisson, D.; Belotti, D.; A very short, efficient and inexpensive synthesis of the prodrug form of SC-54701A a platelet aggregation inhibitor. Bioorg Med Chem Lett 1997, 7, 13, 1699.

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)	11229	1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate	541-41-3	C₃H₅ClO₂	详情	详情
(II)	23897	ethynyl(trimethyl)silane；trimethylsilyl acetylene	1066-54-2	C₅H₁₀Si	详情	详情
(III)	23898	ethyl 3-(trimethylsilyl)-2-propynoate	29394-58-9	C₈H₁₄O₂Si	详情	详情
(IV)	23899	lithium 1-ethoxy-1-ethylenolate		C₄H₇LiO₂	详情	详情
(V)	23900	ethyl 3-oxo-5-(trimethylsilyl)-4-pentynoate		C₁₀H₁₆O₃Si	详情	详情
(VI)	23901	ethyl (3R)-3-hydroxy-5-(trimethylsilyl)-4-pentynoate		C₁₀H₁₈O₃Si	详情	详情
(VIII)	20989	Diethylazadicarboxylate; Diethyl Azodiformate; Azodiformic Acid Diethyl Ester; Diethyl Azodicarboxylate; Azodicarboxylic Acid Diethyl Ester; Diethyl 1,2-diazenedicarboxylate	1972-28-7	C₆H₁₀N₂O₄	详情	详情
(IX)	23904	ethyl (3S)-3-amino-5-(trimethylsilyl)-4-pentynoate		C₁₀H₁₉NO₂Si	详情	详情
(X)	16297	ethyl (3S)-3-amino-4-pentynoate		C₇H₁₁NO₂	详情	详情
(XI)	16296	4-[4-[amino(imino)methyl]anilino]-4-oxobutyric acid		C₁₁H₁₃N₃O₃	详情	详情
(XII)	16295	4-aminobenzenecarboximidamide hydrochloride; 4-aminobenzamidine	3858-83-1	C₇H₉N₃	详情	详情
(XIII)	11291	Dihydro-2,5-furandione; Succinic anhydride	108-30-5	C₄H₄O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Bromination of the coumarin derivative (I) with Br2 in DMF afforded the bromo coumarin (II). Diels-Alder cycloaddition between bromo coumarin (II) and ethyl 3-(trimethylsilyl)propiolate (III) with concomitant decarboxylation furnished the tetrahydronaphthalene (IV). After desilylation of (IV) with trifluoroacetic acid, the resultant ester (V) was reduced to alcohol (VI) using the combination LiAlH4-AlCl3. Further oxidation of the alcohol function of (VI) to aldehyde (VII) was performed with 4-benzylpyridinium dichromate (BPDC) in CH2Cl2. Wittig reaction of aldehyde (VII) with methyl (triphenylphosphoranylidene)acetate produced the arylacrylate ester (VIII), which was then reduced to the saturated ester (IX) employing NaBH4 in the presence of CoCl2.

参考文献中间体

合成目标

【1】 Cimetiere, B.; et al.; Discovery of new combined 5-HT2 and TP-receptor antagonists. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 57.

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)	19586	4-chloro-N-(2-oxo-5,6,7,8-tetrahydro-2H-chromen-6-yl)benzenesulfonamide		C₁₅H₁₄ClNO₄S	详情	详情
(II)	19587	N-(3-bromo-2-oxo-5,6,7,8-tetrahydro-2H-chromen-6-yl)-4-chlorobenzenesulfonamide		C₁₅H₁₃BrClNO₄S	详情	详情
(III)	23898	ethyl 3-(trimethylsilyl)-2-propynoate	29394-58-9	C₈H₁₄O₂Si	详情	详情
(IV)	49920	ethyl 3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-2-(trimethylsilyl)-5,6,7,8-tetrahydro-1-naphthalenecarboxylate		C₂₂H₂₇BrClNO₄SSi	详情	详情
(V)	49921	ethyl 3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenecarboxylate		C₁₉H₁₉BrClNO₄S	详情	详情
(VI)	19590	N-[7-bromo-5-(hydroxymethyl)-1,2,3,4-tetrahydro-2-naphthalenyl]-4-chlorobenzenesulfonamide		C₁₇H₁₇BrClNO₃S	详情	详情
(VII)	19591	N-(7-bromo-5-formyl-1,2,3,4-tetrahydro-2-naphthalenyl)-4-chlorobenzenesulfonamide		C₁₇H₁₅BrClNO₃S	详情	详情
(VIII)	49922	methyl (E)-3-(3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenyl)-2-propenoate		C₂₀H₁₉BrClNO₄S	详情	详情
(IX)	49923	methyl 3-(3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenyl)propanoate		C₂₀H₂₁BrClNO₄S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

参考文献中间体

合成目标

【1】 Cimetiere, B.; et al.; Discovery of new combined 5-HT2 and TP-receptor antagonists. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 57.

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)	19586	4-chloro-N-(2-oxo-5,6,7,8-tetrahydro-2H-chromen-6-yl)benzenesulfonamide		C₁₅H₁₄ClNO₄S	详情	详情
(II)	19587	N-(3-bromo-2-oxo-5,6,7,8-tetrahydro-2H-chromen-6-yl)-4-chlorobenzenesulfonamide		C₁₅H₁₃BrClNO₄S	详情	详情
(III)	23898	ethyl 3-(trimethylsilyl)-2-propynoate	29394-58-9	C₈H₁₄O₂Si	详情	详情
(IV)	49920	ethyl 3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-2-(trimethylsilyl)-5,6,7,8-tetrahydro-1-naphthalenecarboxylate		C₂₂H₂₇BrClNO₄SSi	详情	详情
(V)	49921	ethyl 3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenecarboxylate		C₁₉H₁₉BrClNO₄S	详情	详情
(VI)	19590	N-[7-bromo-5-(hydroxymethyl)-1,2,3,4-tetrahydro-2-naphthalenyl]-4-chlorobenzenesulfonamide		C₁₇H₁₇BrClNO₃S	详情	详情
(VII)	19591	N-(7-bromo-5-formyl-1,2,3,4-tetrahydro-2-naphthalenyl)-4-chlorobenzenesulfonamide		C₁₇H₁₅BrClNO₃S	详情	详情
(VIII)	49922	methyl (E)-3-(3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenyl)-2-propenoate		C₂₀H₁₉BrClNO₄S	详情	详情
(IX)	49923	methyl 3-(3-bromo-6-[[(4-chlorophenyl)sulfonyl]amino]-5,6,7,8-tetrahydro-1-naphthalenyl)propanoate		C₂₀H₂₁BrClNO₄S	详情	详情

Extended Information