1-(2-chloroethyl)azepane -Drug Synthesis Database

【结构式】

【分子编号】22918

【品名】1-(2-chloroethyl)azepane

【CA登记号】

【分子式】C₈H₁₆ClN

【分子量】161.67448

【元素组成】C 59.43% H 9.98% Cl 21.93% N 8.66%

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)

4-Chloro-alpha-methylbenzhydrol (I) is alkylated with N-(2-chloroethyl)hexamethyleneimine (II) in benzene in the presence of sodium amide to give setastine. The starting products are obtained as follows; Caprolactame (III) is O-alkylated with dimethyl sulfate to yield the lactimether (IV), which is reduced with sodium borohydride to hexamethyleneimine (II). Friedel Cratts acylation of chlorobenzene (V) with benzoyl chloride (VI) affords the benzophenone (VII), to which methylmagnesium bromide is added to give the carbinol (I).

参考文献中间体

合成目标

【1】 Rakoczi, J.; Bolla, K.; Beck, I.; Porszasz, K. (Egis Pharmaceuticals Ltd.); New benzhydryloxy-alkylamine derivs. and process f. DE 2528194; GB 1463038 .
【2】 Nogradi, M.; Setastine hydrochloride. Drugs Fut 1987, 12, 4, 357.

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)	22917	1-(4-chlorophenyl)-1-phenyl-1-ethanol		C₁₄H₁₃ClO	详情	详情
(II)	22918	1-(2-chloroethyl)azepane		C₈H₁₆ClN	详情	详情
(III)	22919	2-azepanone	105-60-2	C₆H₁₁NO	详情	详情
(IV)	22920	7-methoxy-3,4,5,6-tetrahydro-2H-azepine; methyl 3,4,5,6-tetrahydro-2H-azepin-7-yl ether	2525-16-8	C₇H₁₃NO	详情	详情
(V)	10190	1-Chlorobenzene	108-90-7	C₆H₅Cl	详情	详情
(VI)	10463	Benzoyl chloride	98-88-4	C₇H₅ClO	详情	详情
(VII)	22923	(4-chlorophenyl)(phenyl)methanone; 4-Chlorobenzophenone	134-85-0	C₁₃H₉ClO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Alkylation of 4-hydroxybenzaldehyde (I) with chloro derivative (II) by means of K2CO3 in DMF at reflux affords benzaldehyde derivative (III), which is reduced with NaBH4 in MeOH to provide the benzylic alcohol (IV) --alternatively, alcohol (IV) can be obtained by reaction of 4-hydroxybenzyl alcohol (V) with chloro derivative (II) by means of NaOH and benzyltriethylammonium bromide in toluene--. Alcohol (V) is treated with HCl in THF and then chlorinated with SOCl2 to furnish hydrochloride salt (VI), which is condensed with the indole derivative (VII) – produced by condensation of the bromo ketone (VIII) and 4-benzyloxyaniline hydrochloride (IX) either refluxing by with DMF or with Et3N in refluxing DMF – by means of NaH in DMF to give the N-alkylated indole (X). Finally, the O-benzyl protecting groups of (X) are removed by transfer hydrogenolysis using cyclohexadiene and Pd/C.

参考文献中间体

合成目标

【1】 Miller, C.P.; Collini, M.D.; Tran, B.D.; et al.; Design, synthesis, and preclinical characterization of novel, highly selective indole estrogens. J Med Chem 2001, 44, 11, 1654.
【2】 Vid, G.; Potoski, J.R.; Raveendranath, P.; Zeldis, J.; Ren, J. (American Home Products Corp.); Novel aryloxy-alkyl-dialkylamines. EP 1025077; WO 9919293 .

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)	13433	4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde	123-08-0	C₇H₆O₂	详情	详情
(II)	22918	1-(2-chloroethyl)azepane		C₈H₁₆ClN	详情	详情
(III)	60165	4-[2-(1-azepanyl)ethoxy]benzaldehyde		C₁₅H₂₁NO₂	详情	详情
(IV)	60166	{4-[2-(1-azepanyl)ethoxy]phenyl}methanol		C₁₅H₂₃NO₂	详情	详情
(V)	29474	4-(hydroxymethyl)phenol; 4-hydroxyphenylmethanol 4-hydroxybenzenemethanol; 4-Hydroxybenzyl alcohol	623-05-2	C₇H₈O₂	详情	详情
(VI)	60167	1-{2-[4-(chloromethyl)phenoxy]ethyl}azepane; 2-(1-azepanyl)ethyl 4-(chloromethyl)phenyl ether		C₁₅H₂₂ClNO	详情	详情
(VII)	38490	5-(benzyloxy)-2-[4-(benzyloxy)phenyl]-3-methyl-1H-indole; benzyl 4-[5-(benzyloxy)-3-methyl-1H-indol-2-yl]phenyl ether		C₂₉H₂₅NO₂	详情	详情
(VIII)	38489	4-Benzyloxy-alpha-bromopropiophenone; 1-[4-(benzyloxy)phenyl]-2-bromo-1-propanone; alpha-Bromo-4-benzyloxy propiophenone	54081-45-9	C₁₆H₁₅BrO₂	详情	详情
(IX)	22460	4-(benzyloxy)aniline; 4-(benzyloxy)phenylamine		C₁₃H₁₃NO	详情	详情
(X)	38495	1-[4-[2-(1-azepanyl)ethoxy]benzyl]-5-(benzyloxy)-2-[4-(benzyloxy)phenyl]-3-methyl-1H-indole; 4-[1-[4-[2-(1-azepanyl)ethoxy]benzyl]-5-(benzyloxy)-3-methyl-1H-indol-2-yl]phenyl benzyl ether		C₄₄H₄₆N₂O₃	详情	详情

Extended Information