ethyl 3-(methylamino)propanoate -Drug Synthesis Database

【结构式】

【分子编号】20771

【品名】ethyl 3-(methylamino)propanoate

【CA登记号】

【分子式】C₆H₁₃NO₂

【分子量】131.17476

【元素组成】C 54.94% H 9.99% N 10.68% O 24.39%

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：(II)

2-Pyrrolecarboxylic acid (I) was condensed with ethyl 3-(methylamino)-propionate (II) by means of diethyl phosphorocyanidate to give amide (III). Alkaline hydrolysis of the ethyl ester group of (III) provided carboxylic acid (IV), which was cyclized in 80% polyphosphoric acid at 100 C to afford the pyrroloazepine (V). Subsequent reaction of (V) with 1,4-dichlorobutane (VI) in the presence of K2CO3 yielded the N-(4-chlorobutyl)pyrrole (VII). Treatment of (VII) with hydroxylamine hydrochloride and NaOAc furnished the E-oxime (VIII) as the major isomer. Then, displacement of the chloro atom of (VIII) with 4-(4-fluorobenzoyl)piperidine-HCl (IX) using K2CO3 and NaI yielded the title compound.

参考文献中间体

合成目标

【1】 Miya, M.; Miyazaki, T.; Inomata, N.; Tatsuoka, T.; Mizuno, A.; Kamei, T.; Takiguchi, C.; Yoshida, M.; Shibata, M.; Synthesis and pharmacological evaluation of pyrroloazepine derivatives as potent antihypertensive agents with antiplatelet aggregation activity. Chem Pharm Bull 1999, 47, 2, 246.

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)	31796	Pyrrole-2-carboxylic acid; 1H-pyrrole-2-carboxylic acid	634-97-9	C₅H₅NO₂	详情	详情
(II)	20771	ethyl 3-(methylamino)propanoate		C₆H₁₃NO₂	详情	详情
(III)	31797	ethyl 3-[methyl(1H-pyrrol-2-ylcarbonyl)amino]propanoate		C₁₁H₁₆N₂O₃	详情	详情
(IV)	31798	N-methyl-N-(1H-pyrrol-2-ylcarbonyl)-beta-alanine		C₉H₁₂N₂O₃	详情	详情
(V)	31799	7-methyl-6,7-dihydropyrrolo[2,3-c]azepine-4,8(1H,5H)-dione		C₉H₁₀N₂O₂	详情	详情
(VI)	31800	1,4-dichlorobutane	110-56-5	C₄H₈Cl₂	详情	详情
(VII)	31801	1-(4-chlorobutyl)-7-methyl-6,7-dihydropyrrolo[2,3-c]azepine-4,8(1H,5H)-dione		C₁₃H₁₇ClN₂O₂	详情	详情
(VIII)	31802	1-(4-chlorobutyl)-7-methyl-6,7-dihydropyrrolo[2,3-c]azepine-4,8(1H,5H)-dione 4-oxime		C₁₃H₁₈ClN₃O₂	详情	详情
(IX)	21497	(4-Fluorophenyl)(4-piperidinyl)methanone; 4-(4-Fluorobenzoyl)piperidine; 4-(p-Fluorobenzoyl)piperidine	56346-57-7	C₁₂H₁₄FNO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

The reaction of benzaldehyde (I) with the sulfoxide (II) by means of benzyltrimethylammonium hydroxide in methanol gives the styrene derivative (III), which is hydrolyzed with HCl in methanol to the phenylacetate (IV). The condensation of (IV) with dimethyl oxalate by means of NaH in THF yields the succinate (V), which by reaction with formaldehyde and K2CO3 is converted into the acrylate (VI). The condensation of (VI) with ethyl 3-(methylamino)propionate gives intermediate (VII), which is cyclized by means of NaH in refluxing toluene yielding the piperidinone (IX). The condensation of (IX) with trimethyl phosphonoacetate (X) by means of NaH in THF affords the expected piperidinyleneacetate (XI), which is reduced with H2 over Pd/C in methanol giving the piperidinylacetate (XII). The cyclization of (XII) by means of polyphosphoric acid (PPA) in refluxing toluene yields the benzoisoquinoline (XIII), which is finally selectively demethylated with BBr3 in methylene chloride to the target compound.

参考文献中间体

合成目标

【1】 Stadler, H.; Bos, M.; Wichmann, J. (F. Hoffmann-La Roche AG); Tricyclic benzo[e]isoindoles and benzo[h]isoquinolines . EP 0958285; JP 2000507965; WO 9830546 .

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)	20754	4-ethyl-3,5-dimethoxybenzaldehyde		C₁₁H₁₄O₃	详情	详情
(II)	20766	methyl (methylsulfanyl)methyl sulfoxide; methyl[(methylsulfanyl)methyl]oxo-lambda(4)-sulfane	33577-16-1	C₃H₈OS₂	详情	详情
(III)	20767	methyl (Z)-2-(4-ethyl-3,5-dimethoxyphenyl)-1-(methylsulfanyl)-1-ethenesulfenate		C₁₄H₂₀O₃S₂	详情	详情
(IV)	20768	methyl 2-(4-ethyl-3,5-dimethoxyphenyl)acetate		C₁₃H₁₈O₄	详情	详情
(V)	20769	dimethyl 2-(4-ethyl-3,5-dimethoxyphenyl)-3-oxosuccinate		C₁₆H₂₀O₇	详情	详情
(VI)	20770	methyl 2-(4-ethyl-3,5-dimethoxyphenyl)acrylate		C₁₄H₁₈O₄	详情	详情
(VII)	20771	ethyl 3-(methylamino)propanoate		C₆H₁₃NO₂	详情	详情
(VIII)	20772	methyl 3-[(3-ethoxy-3-oxopropyl)(methyl)amino]-2-(4-ethyl-3,5-dimethoxyphenyl)propanoate		C₂₀H₃₁NO₆	详情	详情
(IX)	20773	3-(4-ethyl-3,5-dimethoxyphenyl)-1-methyl-4-piperidinone		C₁₆H₂₃NO₃	详情	详情
(X)	13272	Methyl 2-(dimethoxyphosphoryl)acetate; Trimethyl phosphoroacetate	5927-18-4	C₅H₁₁O₅P	详情	详情
(XI)	20775	methyl 2-[3-(4-ethyl-3,5-dimethoxyphenyl)-1-methyl-4-piperidinylidene]acetate		C₁₉H₂₇NO₄	详情	详情
(XII)	20776	methyl 2-[3-(4-ethyl-3,5-dimethoxyphenyl)-1-methyl-4-piperidinyl]acetate		C₁₉H₂₉NO₄	详情	详情
(XIII)	20777	(4aR,10bS)-8-ethyl-7,9-dimethoxy-2-methyl-1,3,4,4a,5,10b-hexahydrobenzo[h]isoquinolin-6(2H)-one		C₁₈H₂₅NO₃	详情	详情

Extended Information