5-bromo-2-(3,4-dimethoxyphenyl)-2-isopropylpentanenitrile -Drug Synthesis Database

【结构式】

【分子编号】30392

【品名】5-bromo-2-(3,4-dimethoxyphenyl)-2-isopropylpentanenitrile

【CA登记号】

【分子式】C₁₆H₂₂BrNO₂

【分子量】340.26022

【元素组成】C 56.48% H 6.52% Br 23.48% N 4.12% O 9.4%

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：(III)

Reaction of 2-(3,4-dimethoxyphenyl)-3-methylbutyronitrile (I) with 1,3-dibromopropane (II) in the presence of n-butyllithium at -78 C provided bromonitrile (III). Alkylation of potassium phthalimide (V) with 9-(chloromethyl)anthracene (IV) yielded the N-alkylated phthalimide (VI), and subsequent hydrazinolysis gave the aminomethyl compound (VIII). Finally, amine (VIII) was alkylated with bromide (III) in Et3N at 60 C to produce the title compound, which was isolated as the corresponding hydrochloride salt.

参考文献中间体

合成目标

【1】 Teodori, E.; Dei, S.; Quidu, P.; et al.; Design, synthesis, and in vitro activity of catamphiphilic reverters of multidrug resistance: Discovery of a selective, highly efficacious chemosensitizer with potency in the nanomolar range. J Med Chem 1999, 42, 10, 1687.

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)	30391	2-(3,4-dimethoxyphenyl)-3-methylbutanenitrile; alpha-Isopropylveratryl cyanide	20850-49-1	C₁₃H₁₇NO₂	详情	详情
(II)	12581	1,3-Dibromopropane	109-64-8	C₃H₆Br₂	详情	详情
(III)	30392	5-bromo-2-(3,4-dimethoxyphenyl)-2-isopropylpentanenitrile		C₁₆H₂₂BrNO₂	详情	详情
(IV)	30393	9-(chloromethyl)anthracene	24463-19-2	C₁₅H₁₁Cl	详情	详情
(V)	27890	Potassium phthalimide	1074-82-4	C₈H₄KNO₂	详情	详情
(VI)	30394	2-(9-anthrylmethyl)-1H-isoindole-1,3(2H)-dione		C₂₃H₁₅NO₂	详情	详情
(VII)	30395	9-anthrylmethanamine; 9-anthrylmethylamine	2476-68-8	C₁₅H₁₃N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Alkylation of the lithium salt of 2-(3,4-dimethoxyphenyl)isobutyronitrile (I) with 1,3-dibromopropane (II) gave the bromo nitrile (III). Conversion of bromide (III) into the desired primary amine (VI) was achieved through a Gabriel synthesis by condensation with potassium phthalimide (IV), followed by hydrazinolysis of the resultant N-substituted phthalimide (V). A two-step procedure was finally employed for the reductive alkylation of amine (VI), consisting of condensation between amine (VI) and the bromo fluorenone (VII) in the presence of titanium isopropoxide and then reduction of the intermediate (VIII) with NaBH3CN.

参考文献中间体

合成目标

【1】 Dei, S.; et al.; Structure-activity relationships and optimisation of the selective MDR modulator 2-(3,4-dimethoxyphenyl)-5-(9-fluorenylamino)-2-(methylethyl) pentanenitrile and its N-methyl derivative. Bioorg Med Chem 2001, 9, 10, 2673.
【2】 Teodori, E.; Dei, S.; Quidu, P.; et al.; Design, synthesis, and in vitro activity of catamphiphilic reverters of multidrug resistance: Discovery of a selective, highly efficacious chemosensitizer with potency in the nanomolar range. J Med Chem 1999, 42, 10, 1687.

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)	30391	2-(3,4-dimethoxyphenyl)-3-methylbutanenitrile; alpha-Isopropylveratryl cyanide	20850-49-1	C₁₃H₁₇NO₂	详情	详情
(II)	12581	1,3-Dibromopropane	109-64-8	C₃H₆Br₂	详情	详情
(III)	30392	5-bromo-2-(3,4-dimethoxyphenyl)-2-isopropylpentanenitrile		C₁₆H₂₂BrNO₂	详情	详情
(IV)	27890	Potassium phthalimide	1074-82-4	C₈H₄KNO₂	详情	详情
(V)	53369	2-(3,4-dimethoxyphenyl)-5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-2-isopropylpentanenitrile	n/a	C₂₄H₂₆N₂O₄	详情	详情
(VI)	53370	5-amino-2-(3,4-dimethoxyphenyl)-2-isopropylpentanenitrile	n/a	C₁₆H₂₄N₂O₂	详情	详情
(VII)	53371	2-Bromo-9-fluorenone	3096-56-8	C₁₃H₇BrO	详情	详情
(VIII)	53372	5-({2-bromo-9-[(triisopropylsilyl)oxy]-9H-fluoren-9-yl}amino)-2-(3,4-dimethoxyphenyl)-2-isopropylpentanenitrile	n/a	C₃₈H₅₁BrN₂O₃Si	详情	详情

Extended Information