4-Chlorobutyraldehyde dimethylacetal; 4-Chloro-1-methoxybutyl methyl ether; 4-Chloro-1,1-dimethoxybutane -Drug Synthesis Database

【结构式】

【分子编号】16870

【品名】4-Chlorobutyraldehyde dimethylacetal; 4-Chloro-1-methoxybutyl methyl ether; 4-Chloro-1,1-dimethoxybutane

【CA登记号】

【分子式】C₆H₁₃ClO₂

【分子量】152.62072

【元素组成】C 47.22% H 8.59% Cl 23.23% O 20.97%

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：(I)

Almotriptan has been obtained by several related ways: 1) The hydrolysis of 4-chlorobutyraldehyde dimethylacetal (I) with HCl gives the corresponding aldehyde (II), which is condensed with 4-(1-pyrrolidinylsulfonylmethyl)phenylhydrazine (III) by means of HCl in methanol/water, giving 3-(2-aminoethyl)-5-(1-pyrrolidinylsulfonylmethyl)-1H-indole (IV). Finally, this compound is methylated with formaldehyde and NaBH4 in methanol. 2) The direct condensation of 4-chlorobutyraldehyde dimethylacetal (I) with 4-(1-pyrrolidinylsulfonylmethyl)phenylhydrazine (III) by means of HCl in water also yields intermediate 3-(2-aminoethyl)-5-(1-pyrrolidinylsulfonylmethyl)-1H-indole (IV). 3) The decarboxylation of 3-[2-(dimethylamino)ethyl]-5-(1-pyrrolidinylsulfonylmethyl)-1H-indole-2-carboxylic acid (V) catalyzed by means of Cu2O in quinoline at 190 C also gives almotriptan.

参考文献中间体

合成目标

【1】 Fernandez Forner, D.; Puig Duran, C.; Prieto Soto, J.; Vega Noverola, A.; Moragues Mauri, J. (Almirall Prodesfarma, SA); Indol derivs. for the treatment of migraine. EP 0605697; JP 1994511261; US 5565447; WO 9402460 .
【2】 Fernandez Forner, M.D.; Puig Duran, C.; Crespo Crespo, M.I.; Moragues Mauri, J. (Almirall Prodesfarma, SA); Process for the preparation of indole derivs.. ES 2084560 .
【3】 Pujol Noguera, F.; Crespo Crespo, M.I.; Puig Duran, C.; Fernandez Forner, D.; Moragues Mauri, J. (Almirall Prodesfarma, SA); New indole derivs.. ES 2056025 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	16870	4-Chlorobutyraldehyde dimethylacetal; 4-Chloro-1-methoxybutyl methyl ether; 4-Chloro-1,1-dimethoxybutane	C₆H₁₃ClO₂	详情	详情
(II)	23428	4-Chlorobutanal	C₄H₇ClO	详情	详情
(III)	23429	1-[(4-hydrazinobenzyl)sulfonyl]pyrrolidine	C₁₁H₁₇N₃O₂S	详情	详情
(IV)	23430	2-[5-[(1-pyrrolidinylsulfonyl)methyl]-1H-indol-3-yl]-1-ethanamine; 2-[5-[(1-pyrrolidinylsulfonyl)methyl]-1H-indol-3-yl]ethylamine	C₁₅H₂₁N₃O₂S	详情	详情
(V)	23431	3-[2-(dimethylamino)ethyl]-5-[(1-pyrrolidinylsulfonyl)methyl]-1H-indole-2-carboxylic acid	C₁₈H₂₅N₃O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

2) The condensation of 4-nitrobenzyl bromide (VI) with 1,2,4-triazole sodium salt (VII) in DMF gives 1-(4-nitrobenzyl)-1,2,4-triazole (VIII), which is reduced with H2 over Pd/C in ethanol/ethyl acetate yielding the aniline (I). The diazotization of (I) with NaNO2/HCl followed by reduction with SnCl2 affords the corresponding hydrazine (IX), which is cyclized with 4-chlorobutanal dimethylacetal (X) by means of HCl in refluxing ethanol/water to afford 2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl] ethylamine (XI). Finally, this amine is methylated with formaldehyde, sodium cyanoborohydride and acetic acid in methanol.

参考文献中间体

合成目标

【1】 Castañer, J.; Mealy, N.; Rabassseda, X.; MK-0462. Drugs Fut 1995, 20, 7, 676.
【2】 Baker, R.; Matassa, V.G.; Street, L.J. (Merck Sharp & Dohme Ltd.); Imidazole, triazole and tetrazole derivs. EP 0497512; EP 0778275; US 5298520; US 5451588; US 5602162; US 5602163 .

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)	16860	4-(1H-1,2,4-triazol-1-ylmethyl)aniline; 4-(1H-1,2,4-triazol-1-ylmethyl)phenylamine		C₉H₁₀N₄	详情	详情
(VI)	16866	1-(Bromomethyl)-4-nitrobenzene; para-Nitrobenzyl bromide	100-11-8	C₇H₆BrNO₂	详情	详情
(VII)	13104	1,2,4-Triazole, sodium derivative	41253-21-8	C₂H₂N₃Na	详情	详情
(VIII)	16868	1-(4-nitrobenzyl)-1H-1,2,4-triazole		C₉H₈N₄O₂	详情	详情
(IX)	16869	1-(4-hydrazinobenzyl)-1H-1,2,4-triazole		C₉H₁₁N₅	详情	详情
(X)	16870	4-Chlorobutyraldehyde dimethylacetal; 4-Chloro-1-methoxybutyl methyl ether; 4-Chloro-1,1-dimethoxybutane		C₆H₁₃ClO₂	详情	详情
(XI)	16871	2-[5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethylamine; 2-[5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]-1-ethanamine		C₁₃H₁₅N₅	详情	详情

Extended Information