1-methylene-2-propenyl trimethylsilyl ether; trimethyl[(1-methylene-2-propenyl)oxy]silane -Drug Synthesis Database

【结构式】

【分子编号】18557

【品名】1-methylene-2-propenyl trimethylsilyl ether; trimethyl[(1-methylene-2-propenyl)oxy]silane

【CA登记号】38053-91-7

【分子式】C₇H₁₄OSi

【分子量】142.27306

【元素组成】C 59.1% H 9.92% O 11.25% Si 19.74%

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：(V)

Dihydroquinolinone (I) was protected as the tert-butyl carbamate (II) by condensation with di-tert-butyl dicarbonate. Reduction of (II) with NaBH4 in EtOH at -25 C, followed by reaction with ethanolic HCl provided ethoxy compound (III). Subsequent treatment of (III) with 2-silyloxy-1,3-butadiene (V) and trimethylsilyl triflate afforded benzoquinolizinone (VI), through the sequence of Mannich condensation of intermediate N-tert-Boc iminium salt (IV) with silyl enol ether (V), followed by Michael cyclization of the unsaturated ketone. Then, oxidation with mercuric acetate provided the target 4-4a unsaturated compound together with a minor amount of 1,2-unsaturated product.

参考文献中间体

合成目标

【1】 Guarna, A.; Occhiato, E.G.; Scarpi, D.; Tsai, R.; Danza, G.; Comerci, A.; Mancina, R.; Serio, M.; Synthesis of benzo[c]quinolizin-3-ones: Selective non-steroidal inhibitors of steroid 5alpha-reductase 1. Bioorg Med Chem Lett 1998, 8, 20, 2871.

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)	18553	3,4-dihydro-2(1H)-quinolinone	553-03-7	C₉H₉NO	详情	详情
(II)	18554	tert-butyl 2-oxo-3,4-dihydro-1(2H)-quinolinecarboxylate		C₁₄H₁₇NO₃	详情	详情
(III)	18555	tert-butyl 2-ethoxy-3,4-dihydro-1(2H)-quinolinecarboxylate		C₁₆H₂₃NO₃	详情	详情
(IV)	18556	tert-butyl 3,4-dihydro-1lambda(5)-quinoline-1-carboxylate		C₁₄H₁₉NO₂	详情	详情
(V)	18557	1-methylene-2-propenyl trimethylsilyl ether; trimethyl[(1-methylene-2-propenyl)oxy]silane	38053-91-7	C₇H₁₄OSi	详情	详情
(VI)	18558	1,2,4,4a,5,6-hexahydro-3H-pyrido[1,2-a]quinolin-3-one		C₁₃H₁₅NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

Lactam (I) was protected as the tert-butyl carbamate (II) by treatment with Boc2O in the presence of Et3N and DMAP. After reduction of (II) with NaBH4 in EtOH at -25 C, reaction with ethanolic HCl produced the ethoxy derivative (III). Treatment with TiCl4 in CH2Cl2 at -30 C generated the intermediate iminium salt (IV), that was converted into the target benzoquinolizinone system (VI) by the tandem Mannich-Michael condensation with 2-(trimethylsilyloxy)-1,3-butadiene (V). Finally, oxidation of (V) with mercuric acetate produced the desired unsaturated compound.

参考文献中间体

合成目标

【1】 Zorn, C.; Danza, G.; Mancina, R.; Serio, M.; Occhiato, E.G.; Scarpi, D.; Comerci, A.; Guarna, A.; Synthesis of 8-chloro-benzo[c]quinolizin-3-ones as potent and selective inhibitors of human steroid 5alpha-reductase 1. Bioorg Med Chem Lett 2000, 10, 4, 353.

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)	40942	6-chloro-4-methyl-3,4-dihydro-2(1H)-quinolinone		C₁₀H₁₀ClNO	详情	详情
(II)	40943	tert-butyl 6-chloro-4-methyl-2-oxo-3,4-dihydro-1(2H)-quinolinecarboxylate		C₁₅H₁₈ClNO₃	详情	详情
(III)	40944	tert-butyl 6-chloro-2-ethoxy-4-methyl-3,4-dihydro-1(2H)-quinolinecarboxylate		C₁₇H₂₄ClNO₃	详情	详情
(IV)	40945	1-(tert-butoxycarbonyl)-6-chloro-4-methyl-3,4-dihydroquinolinium		C₁₅H₁₉ClNO₂	详情	详情
(V)	18557	1-methylene-2-propenyl trimethylsilyl ether; trimethyl[(1-methylene-2-propenyl)oxy]silane	38053-91-7	C₇H₁₄OSi	详情	详情
(VI)	40946	8-chloro-6-methyl-1,2,4,4a,5,6-hexahydro-3H-pyrido[1,2-a]quinolin-3-one		C₁₄H₁₆ClNO	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

Condensation between (S)-alpha-methylbenzylamine (I) and ethyl glyoxylate (II) afforded imine (III), which was subjected to hetero-Diels-Alder cycloaddition with 2-(trimethylsilyloxy)-1,3-butadiene (IV) producing piperidinecarboxylate (V) as the major diastereoisomer. Ketalization of (V) with triethyl orthoformate gave the corresponding the diethyl acetal (VI). The ester group of (VI) was then reduced to alcohol (VII) employing LiAlH4. Mitsunobu condensation of alcohol (VII) with phthalimide (VIII) gave (IX) which, followed by acidic ketal hydrolysis, furnished (X). Condensation of piperidinone (X) with t-butyl cyanoacetate (XI) in the presence of sulfur and morpholine gave rise to two regioisomeric thienopyridine derivatives (XII) and (XIII), which were separated by column chromatography.

参考文献中间体

合成目标

【1】 Lau, J.; Andersen, H.S.; Newman, M.J.; Hansen, T.K.; Olsen, O.H.; Bakir, F.; Holsworth, D.D.; Axe, F.U.; Ge, Y.; Uyeda, R.T.; Judge, L.M.; Moeller, N.P.H.; Shapira, B.Z. (Novo Nordisk A/S; Ontogen Corp.); Modulators of protein tyrosine phosphatases (PTPases). WO 0204459 .

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)	20042	(1S)-1-phenyl-1-ethanamine; (1S)-1-phenylethylamine		C₈H₁₁N	详情	详情
(II)	48591	Ethyl glyoxylate; Ethyl oxoacetate; Glyoxylic acid ethyl ester	924-44-7	C₄H₆O₃	详情	详情
(III)	58785	ethyl 2-{[(1S)-1-phenylethyl]imino}acetate		C₁₂H₁₅NO₂	详情	详情
(IV)	18557	1-methylene-2-propenyl trimethylsilyl ether; trimethyl[(1-methylene-2-propenyl)oxy]silane	38053-91-7	C₇H₁₄OSi	详情	详情
(V)	58786	ethyl (2R)-4-oxo-1-[(1S)-1-phenylethyl]-2-piperidinecarboxylate		C₁₆H₂₁NO₃	详情	详情
(VI)	58787	ethyl (2R)-4,4-diethoxy-1-[(1S)-1-phenylethyl]-2-piperidinecarboxylate		C₂₀H₃₁NO₄	详情	详情
(VII)	58788	{(2R)-4,4-diethoxy-1-[(1S)-1-phenylethyl]piperidinyl}methanol		C₁₈H₂₉NO₃	详情	详情
(VIII)	12376	Phthalimide; 1H-Isoindole-1,3(2H)-dione; Isoindole-1,3-dione;Phthalic dicarboximide;Phenylimide;Isoindole-1,3-dione	85-41-6	C₈H₅NO₂	详情	详情
(IX)	58789	2-({(2R)-4,4-diethoxy-1-[(1S)-1-phenylethyl]piperidinyl}methyl)-1H-isoindole-1,3(2H)-dione		C₂₆H₃₂N₂O₄	详情	详情
(X)	58790	2-({(2R)-4-oxo-1-[(1S)-1-phenylethyl]piperidinyl}methyl)-1H-isoindole-1,3(2H)-dione		C₂₂H₂₂N₂O₃	详情	详情
(XI)	14330	tert-Butyl cyanoacetate; tert-butyl 2-cyanoacetate	1116-98-9	C₇H₁₁NO₂	详情	详情
(XII)	58791	tert-butyl (7S)-2-amino-7-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-6-[(1S)-1-phenylethyl]-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylate		C₂₉H₃₁N₃O₄S	详情	详情
(XIII)	58792	tert-butyl (5R)-2-amino-5-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-6-[(1S)-1-phenylethyl]-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylate		C₂₉H₃₁N₃O₄S	详情	详情

Extended Information