4,6-dimethyl-1H-indole -Drug Synthesis Database

【结构式】

【分子编号】40795

【品名】4,6-dimethyl-1H-indole

【CA登记号】

【分子式】C₁₀H₁₁N

【分子量】145.20408

【元素组成】C 82.72% H 7.64% N 9.65%

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)

The reduction of 4,6-dimethylindole (I) with NaBH3CN in AcOH produced indoline (II), which was acetylated with Ac2O to give amide (III). Introduction of a blocking group at position 5 of (III) was effected by bromination in AcOH, yielding (IV). Then, nitration of (IV) with HNO3/H2SO4 furnished the 7-nitroindoline (V). After basic hydrolysis of the acetamide group of (V), the resulting indoline (VI) was N-alkylated with n-pentyl bromide (VII) and NaH to afford (VIII). Reduction of the nitro group of (VIII) with simultaneous hydrogenolysis of the bromine atom was carried out by hydrogenation over Pd/C to produce amino indoline (IX). Finally, the title amide was obtained by coupling of (IX) with pivaloyl chloride in the presence of Et3N.

参考文献中间体

合成目标

【1】 Matsui, H.; Kamiya, S.; Shirahase, H.; Nakamura, S.; Wada, K. (Kyoto Pharmaceutical Industries, Ltd.); Novel heterocyclic derivs., process for producing the same, and medicinal use thereof. EP 0782986; JP 1996092210; US 5990150; WO 9609287 .

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)	40795	4,6-dimethyl-1H-indole		C₁₀H₁₁N	详情	详情
(II)	40796	4,6-dimethylindoline		C₁₀H₁₃N	详情	详情
(III)	40797	1-(4,6-dimethyl-2,3-dihydro-1H-indol-1-yl)-1-ethanone		C₁₂H₁₅NO	详情	详情
(IV)	40798	1-(5-bromo-4,6-dimethyl-2,3-dihydro-1H-indol-1-yl)-1-ethanone		C₁₂H₁₄BrNO	详情	详情
(V)	40799	1-(5-bromo-4,6-dimethyl-7-nitro-2,3-dihydro-1H-indol-1-yl)-1-ethanone		C₁₂H₁₃BrN₂O₃	详情	详情
(VI)	40800	5-bromo-4,6-dimethyl-7-nitroindoline		C₁₀H₁₁BrN₂O₂	详情	详情
(VII)	14460	1-bromopentane; n-Amyl Bromide	110-53-2	C₅H₁₁Br	详情	详情
(VIII)	40801	5-bromo-4,6-dimethyl-7-nitro-1-pentylindoline		C₁₅H₂₁BrN₂O₂	详情	详情
(IX)	40802	4,6-dimethyl-1-pentyl-2,3-dihydro-1H-indol-7-ylamine; 4,6-dimethyl-1-pentyl-7-indolinamine		C₁₅H₂₄N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

4,6-Dimethylindole (I) is reduced to the corresponding indoline (II) with NaBH3CN in AcOH. After acylation with Ac2O, the resultant N-acetylindoline (III) is brominated by means of Br2 in AcOH to give the 5-bromoindoline derivative (IV). Nitration of (IV) with fuming HNO3 in H2SO4/AcOH provides the 7-nitro indoline (V). Then, simultaneous debromination and nitro group reduction in (V) is accomplished by hydrogenation in the presence of Pd/C to furnish aniline (VI). Further acylation of (VI) with pivaloyl chloride leads to diamide (VII). The N-acetyl group of (VII) is selectively removed under alkaline hydrolysis conditions to yield indoline (VIII). Finally, alkylation of (VIII) with 1-bromodecane and K2CO3 furnishes the title compound.

参考文献中间体

合成目标

【1】 Yoshimi, A.; Kasai, M.; Shirahase, H.; Matsui, H.; Kanda, M.; Kurahashi, K.; Kamiya, S.; Takahashi, K.; Nakamura, S.; Bioavailable acyl-CoA: Cholesterol acyltransferase inhibitor with anti-peroxidative activity: Synthesis and biological activity of novel indolinyl amide and urea derivatives. Chem Pharm Bull 2000, 48, 6, 817.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	40795	4,6-dimethyl-1H-indole	C₁₀H₁₁N	详情	详情
(II)	40796	4,6-dimethylindoline	C₁₀H₁₃N	详情	详情
(III)	40797	1-(4,6-dimethyl-2,3-dihydro-1H-indol-1-yl)-1-ethanone	C₁₂H₁₅NO	详情	详情
(IV)	40798	1-(5-bromo-4,6-dimethyl-2,3-dihydro-1H-indol-1-yl)-1-ethanone	C₁₂H₁₄BrNO	详情	详情
(V)	40799	1-(5-bromo-4,6-dimethyl-7-nitro-2,3-dihydro-1H-indol-1-yl)-1-ethanone	C₁₂H₁₃BrN₂O₃	详情	详情
(VI)	62806	1-(7-amino-4,6-dimethyl-2,3-dihydro-1H-indol-1-yl)-1-ethanone	C₁₂H₁₆N₂O	详情	详情
(VII)	62807	N-(1-acetyl-4,6-dimethyl-2,3-dihydro-1H-indol-7-yl)-2,2-dimethylpropanamide	C₁₇H₂₄N₂O₂	详情	详情
(VIII)	62808	N-(4,6-dimethyl-2,3-dihydro-1H-indol-7-yl)-2,2-dimethylpropanamide	C₁₅H₂₂N₂O	详情	详情

Extended Information