【结 构 式】 |
【分子编号】45904 【品名】5-bromo-4,6-dimethyl-1-octyl-7-indolinamine; 5-bromo-4,6-dimethyl-1-octyl-2,3-dihydro-1H-indol-7-ylamine 【CA登记号】 |
【 分 子 式 】C18H29BrN2 【 分 子 量 】353.34574 【元素组成】C 61.19% H 8.27% Br 22.61% N 7.93% |
合成路线1
该中间体在本合成路线中的序号:(VIII)Indole derivative (I) is converted into acetyl indoline (II) by first reduction with NaBH3CN in HOAc followed by acetylation with Ac2O in benzene or in CHCl3. Bromination of (II) with Br2 in HOAc yields derivative (III), which is then nitrated with fuming nitric acid in H2SO4/HOAc or with HNO3/Ac2O to afford nitroindoline (IV). Removal of the acetyl group of (IV) by means of NaOH or HCl in MeOH, followed by alkylation of the resulting indoline with NaH and octyl iodide (V) or octyl bromide (VI) in DMF, provides derivative (VII). Hydrogenation of (VII) over Pd/C in MeOH or benzene yields aminoindoline derivative (VIII), which is finally condensed with pivaloyl chloride (IX) in CHCl3 in the presence of Et3N to furnish the desired compound. Alternatively, conversion of (IV) into the target compound can be achieved as follows: Hydrogenation of the nitro moiety of (IV) over Pd/C in MeOH gives acetyl aminoindoline derivative (X), which is then coupled to pivaloyl chloride (IX) in CHCl3 in the presence of Et3N to afford derivative (XI). Finally, (XI) is hydrolyzed with NaOH in MeOH and the resulting secondary amide is condensed with octyl bromide (VI) in DMF in the presence of K2CO3.
【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 . |
【2】 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 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 40796 | 4,6-dimethylindoline | C10H13N | 详情 | 详情 | |
(II) | 40797 | 1-(4,6-dimethyl-2,3-dihydro-1H-indol-1-yl)-1-ethanone | C12H15NO | 详情 | 详情 | |
(III) | 40798 | 1-(5-bromo-4,6-dimethyl-2,3-dihydro-1H-indol-1-yl)-1-ethanone | C12H14BrNO | 详情 | 详情 | |
(IV) | 40799 | 1-(5-bromo-4,6-dimethyl-7-nitro-2,3-dihydro-1H-indol-1-yl)-1-ethanone | C12H13BrN2O3 | 详情 | 详情 | |
(V) | 45901 | 1-heptyl-1lambda(3)-diiodane | C7H16I2 | 详情 | 详情 | |
(VI) | 45902 | bromo(heptyl)-lambda(3)-iodane | C7H16BrI | 详情 | 详情 | |
(VII) | 45903 | 5-bromo-4,6-dimethyl-7-nitro-1-octylindoline | C18H27BrN2O2 | 详情 | 详情 | |
(VIII) | 45904 | 5-bromo-4,6-dimethyl-1-octyl-7-indolinamine; 5-bromo-4,6-dimethyl-1-octyl-2,3-dihydro-1H-indol-7-ylamine | C18H29BrN2 | 详情 | 详情 | |
(IX) | 13597 | 2,2-Dimethylpropanoyl chloride; Pivaloyl chloride | 3282-30-2 | C5H9ClO | 详情 | 详情 |
(X) | 45905 | 1-(7-amino-5-bromo-4,6-dimethyl-2,3-dihydro-1H-indol-1-yl)-1-ethanone | C12H15BrN2O | 详情 | 详情 | |
(XI) | 45906 | N-(1-acetyl-5-bromo-4,6-dimethyl-2,3-dihydro-1H-indol-7-yl)-2,2-dimethylpropanamide | C17H23BrN2O2 | 详情 | 详情 |