2-(4-iodophenyl)-1-ethanol -Drug Synthesis Database

【结构式】

【分子编号】30973

【品名】2-(4-iodophenyl)-1-ethanol

【CA登记号】

【分子式】C₈H₉IO

【分子量】248.06333

【元素组成】C 38.74% H 3.66% I 51.16% O 6.45%

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：(XI)

The cyclization of 3-hydroxy-1,2-phenylenediamine (I) with 2-phenoxyacetonitrile (II) by means of sodium methoxide in methanol gives the benzimidazole (III), which is acylated with 4-(3-bromopropyl)piperidine-1-carboxylic acid tert-butyl ester (IV) by means of NaH and KI in hot DMF yielding the N-alkylated benzimidazole (V). The alkylation of the hydroxy group of (V) with 1-(3-bromopropyl)piperidine (VI) by means of NaH and KI as before affords the dialkylated benzimidazole (VII), which is deprotected with TFA in dichloromethane affording the free piperidine (VIII). Finally, the piperidine group of (VIII) is alkylated with 2-(4-iodophenyl)ethyl bromide (IX) by means of NaHCO3 in hot DMF.

参考文献中间体

合成目标

【1】 Cantrell, B.E.; Zarrinmayeh, H.; Zimmerman, D.M.; et al.; Structure-activity relationship of a series of diaminoalkyl substituted benzimidazole as neuropeptide Y Y1 receptor antagonists. Bioorg Med Chem Lett 1999, 9, 5, 647.
【2】 Nunes, A.M.; Zarrinmayeh, H.; Ornstein, P.L.; et al.; Synthesis and evaluation of a series of novel 2-[(4-chlorophenoxy)methyl]benzimidazoles as selective neuropeptide Y Y1 receptor antagonists. J Med Chem 1998, 41, 15, 2709.

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)	30964	2,3-diaminophenol		C₆H₈N₂O	详情	详情
(II)	30965	2-phenoxyacetonitrile	3598-14-9	C₈H₇NO	详情	详情
(III)	30966	2-(phenoxymethyl)-1H-benzimidazol-4-ol		C₁₄H₁₂N₂O₂	详情	详情
(IV)	30967	tert-butyl 4-(3-bromopropyl)-1-piperidinecarboxylate		C₁₃H₂₄BrNO₂	详情	详情
(V)	30968	tert-butyl 4-[3-[4-hydroxy-2-(phenoxymethyl)-1H-benzimidazol-1-yl]propyl]-1-piperidinecarboxylate		C₂₇H₃₅N₃O₄	详情	详情
(VI)	30969	1-(3-bromopropyl)piperidine		C₈H₁₆BrN	详情	详情
(VII)	30970	tert-butyl 4-(3-[2-(phenoxymethyl)-4-[3-(1-piperidinyl)propoxy]-1H-benzimidazol-1-yl]propyl)-1-piperidinecarboxylate		C₃₅H₅₀N₄O₄	详情	详情
(VIII)	30971	2-(phenoxymethyl)-1-[3-(4-piperidinyl)propyl]-1H-benzimidazol-4-yl 3-(1-piperidinyl)propyl ether; 2-(phenoxymethyl)-4-[3-(1-piperidinyl)propoxy]-1-[3-(4-piperidinyl)propyl]-1H-benzimidazole		C₃₀H₄₂N₄O₂	详情	详情
(IX)	30972	1-(2-bromoethyl)-4-iodobenzene		C₈H₈BrI	详情	详情
(X)	24298	2-(4-iodophenyl)acetic acid	1798-06-7	C₈H₇IO₂	详情	详情
(XI)	30973	2-(4-iodophenyl)-1-ethanol		C₈H₉IO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

2-Amino-6-bromopyridine (II) was prepared by reaction of 2,6-dibromopyridine (I) with ammonium hydroxide in a pressure bomb at 170 C. The amino group of (III) was subsequently blocked as the pyrrole derivative (IV) by condensation with 2,5-hexanedione (III). Diazotization of p-aminophenyl ethanol (V) followed by treatment with KI gave iodo derivative (VI). Subsequent reaction of (VI) with SOCl2 provided chloride (VII). Arylpyridine (VIII) was obtained by lithiation of bromopyridine (IV) with BuLi, followed by conversion to the corresponding organozinc compound with ZnCl2 and palladium-catalyzed coupling with iodide (VII). Pyrrole ring cleavage in (VIII) upon treatment with hydroxylamine furnished aminopyridine (IX). Subsequent condensation with N-Boc-piperazine (X) provided adduct (XI). After acid cleavage of the Boc group of (XI), alkylation of the resulting piperazine with phenacyl chloride (XII) yielded the title compound. Alternatively, the title compound was obtained by condensation of chloride (IX) with N-phenacylpiperazine (XIII).

参考文献中间体

合成目标

【1】 Qian, W.; Lowe, J.A.; Volkmann, R.A.; et al.; A new class of selective and potent inhibitors of neuronal nitric oxide synthase. Bioorg Med Chem Lett 1999, 9, 17, 2569.
【2】 Lowe, J.A. III; Whittle, P.J. (Pfizer Inc.); 6-Phenylpyridyl-2-amine derivs.. EP 0891332; JP 1999510513; WO 9736871 .

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)	10159	2,6-Dibromopyridine	626-05-1	C₅H₃Br₂N	详情	详情
(II)	41341	2-amino-6-bromopyridine; 6-bromo-2-pyridinamine; 6-bromo-2-pyridinylamine	19798-81-3	C₅H₅BrN₂	详情	详情
(III)	24848	acetonyl acetone;1,2-Diacetylethane;a,b-Diacetylethane;2,5-Diketohexane;Diacetonyl;Acetonylacetone;2,5-Dioxohexane;2,5-hexanedione	110-13-4	C₆H₁₀O₂	详情	详情
(IV)	41342	2-bromo-6-(2,5-dimethyl-1H-pyrrol-1-yl)pyridine		C₁₁H₁₁BrN₂	详情	详情
(V)	14019	p-Aminophenylethanol; 2-(4-Aminophenyl)-1-ethanol	104-10-9	C₈H₁₁NO	详情	详情
(VI)	30973	2-(4-iodophenyl)-1-ethanol		C₈H₉IO	详情	详情
(VII)	41343	1-(2-chloroethyl)-4-iodobenzene		C₈H₈ClI	详情	详情
(VIII)	41344	2-[4-(2-chloroethyl)phenyl]-6-(2,5-dimethyl-1H-pyrrol-1-yl)pyridine		C₁₉H₁₉ClN₂	详情	详情
(IX)	41345	6-[4-(2-chloroethyl)phenyl]-2-pyridinamine; 6-[4-(2-chloroethyl)phenyl]-2-pyridinylamine		C₁₃H₁₃ClN₂	详情	详情
(X)	13225	N-tert-Butoxycarbonyl piperazine; tert-butyl 1-piperazinecarboxylate;tert-butyl piperazine-1-carboxylate	143238-38-4	C₉H₁₈N₂O₂	详情	详情
(XI)	41346	tert-butyl 4-[4-(6-amino-2-pyridinyl)phenethyl]-1-piperazinecarboxylate		C₂₂H₃₀N₄O₂	详情	详情
(XII)	38669	2-chloro-1-phenyl-1-ethanone	532-27-4	C₈H₇ClO	详情	详情
(XIII)	41347	1-phenyl-2-(1-piperazinyl)-1-ethanone		C₁₂H₁₆N₂O	详情	详情

Extended Information