【结 构 式】 |
【分子编号】43791 【品名】methyl (1R,3R)-1-(1,3-benzodioxol-5-yl)-2-(2-chloroacetyl)-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylate 【CA登记号】 |
【 分 子 式 】C22H19ClN2O5 【 分 子 量 】426.85604 【元素组成】C 61.9% H 4.49% Cl 8.31% N 6.56% O 18.74% |
与该中间体有关的原料药合成路线共 3 条
合成路线1
该中间体在本合成路线中的序号:(V)Cyclization of D-tryptophan methyl ester (I) with piperonal (II) by means of TFA in dichloromethane gives, after separation of the undesired trans-isomer by flash chromatography, the (1R,3R-cis)-pyrido-indole derivative (III). The acylation of (III) with chloroacetyl chloride (IV) and NaHCO3 in chloroform yields the chloroacetyl derivative (V), which is finally cyclized with methylamine in methanol.
【1】 Daugan, A.; Grondin, P.; Ruault, C.; et al.; The discovery of tadalafil: A novel and highly selective PDE5 inhibitor. 2: 2,3,6,7,12,12a-Hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione analogues. J Med Chem 2003, 46, 21, 4533. |
【2】 Martin, L.; Sorbera, L.A.; Leeson, P.A.; Castaner, J.; IC-351. Drugs Fut 2001, 26, 1, 15. |
【3】 Daugan, A.C.-M. (Icos Corp.); Tetracyclic derivs., process of preparation and use. EP 0740668; JP 1997508113; US 5859006; US 6025494; US 6127542; WO 9519978 . |
【4】 Daugan, A.C.-M. (Icos Corp.); Use of cGMP-phosphodiesterase inhibitors to treat impotence. JP 1999509221; US 6140329; WO 9703675 . |
【5】 Gellibert, F.; Daugan, A.C.-M. (Icos Corp.); Tetracyclic cyclic GMP-specific phosphodiesterase inhibitors, process of preparation and use. US 6143746 . |
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) | 20416 | methyl (2R)-2-amino-3-(1H-indol-3-yl)propanoate | C12H14N2O2 | 详情 | 详情 | |
(II) | 10127 | 1,3-Benzodioxole-5-carbaldehyde; Heliotropine | 120-57-0 | C8H6O3 | 详情 | 详情 |
(III) | 43790 | methyl (1R,3R)-1-(1,3-benzodioxol-5-yl)-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylate | C20H18N2O4 | 详情 | 详情 | |
(IV) | 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 |
(V) | 43791 | methyl (1R,3R)-1-(1,3-benzodioxol-5-yl)-2-(2-chloroacetyl)-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylate | C22H19ClN2O5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(V)
【1】 Jiang WQ, Alford VC, Qiu YH. 2004. Synthesis and SAR of tetracyclic pyrroloquinolones as phosphodies-terase 5 inhibitors. Bioorg Med Chem, 12(6):1505~1515 |
【2】 Orme MW, Maninelli MJ, Doecke CW, et aL. 2004. Preparation of tetrahydro-β-carboline diastereomers by modified Pictet-Spengler reaction. W0 2004011463 |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(III) | 10127 | 1,3-Benzodioxole-5-carbaldehyde; Heliotropine | 120-57-0 | C8H6O3 | 详情 | 详情 |
(I) | 66756 | (R)-2-amino-3-(1H-indol-3-yl)propanoic acid | C11H12N2O2 | 详情 | 详情 | |
(II) | 66757 | (R)-methyl 2-amino-3-(1H-indol-3-yl)propanoate hydrochloride | C12H14N2O2.HCl | 详情 | 详情 | |
(IV) | 66758 | methyl (1R,3R)-1-(1,3-benzodioxol-5-yl)-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylate hydrochloride | C20H18N2O4.HCl | 详情 | 详情 | |
(V) | 43791 | methyl (1R,3R)-1-(1,3-benzodioxol-5-yl)-2-(2-chloroacetyl)-2,3,4,9-tetrahydro-1H-beta-carboline-3-carboxylate | C22H19ClN2O5 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号: (II)
【1】 Revell JD, Srinivasan N, Ganesan A. 2004. Two concise syntheses of Cialis via the N-acyliminium Pictet-Spengler reaction. Synlett, (8):1428~1430 |
Extended Information