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【结 构 式】 
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【分子编号】12579 【品名】[3-(Dimethylamino)propyl](triphenyl)phosphonium bromide 【CA登记号】 |
【 分 子 式 】C23H27BrNP 【 分 子 量 】428.351882 【元素组成】C 64.49% H 6.35% Br 18.65% N 3.27% P 7.23% |
合成路线1
该中间体在本合成路线中的序号：(V)Reaction of the sodium salt of p-hydroxyphenylacetic acid methyl ester (I) with phthalide (II) gives 2-(4-carboxymethylphenoxymethyl)benzoic acid methyl ester (III), which is cyclized with trifluoroacetic anhydride followed by borontrifluoride etherate to yield 11-oxo-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid methyl ester (IV). Wittig reaction of compound (IV) with 3-(dimethylaminopropyl)triphenylphosphonium bromide hydrobromide (V) yields (Z)-11-[3-(dimethylamino)propylidene]-6,11-dihydrodibenz[b,e]oxepin-2-acetic acid methyl ester (VIII), which is hydrolyzed with NaOH and treated with p-toluenesulfonic acid in isopropanol to afford the p-toluenesulfonate salt (IX), from which the free base is finally liberated. Compound (V) is obtained from (3-bromopropyl)triphenylphosphonium bromide hydrobromide (VI), previously prepared from 1,3-dibromopropane (VII) and triphenylphosphine in toluene.
| 【1】 Iwao, J.; Iso, T.; Oya, M. (Santen Pharmaceutical Co., Ltd.); Novel benzothiazine derivs.. EP 0237573; JP 1987123181; US 4786635; WO 8700838 . |
| 【2】 Oshiam, E.; Kumazawa, T.; Otaki, S.; Obase, H.; Ohmori, K.; Ishii, H.; Manabe, H.; Tamura, T.; Shuto, K. (Kyowa Hakko Kogyo Co., Ltd.); Dibenz[b,e]oxepin deriv. and antiallergic and antiinflammatory agent. EP 0235796; JP 1988010784; US 5116863 . |
| 【3】 Sano, T.; et al.; Process improvement in the production of a pharmaceutical intermediate using a reaction calorimeter for studies on the reaction kinetics of amination of a bromopropyl compound. Org Process Res Dev 1998, 2, 3, 169. |
| 【4】 Yamauchi, H.; Kawashima, Y.; Yamamoto, K.; Ito, S.; Iwao, J.-I.; Fujita, M.; Ota, A.; Kato, N.; Synthesis and Ca2+ antagonistic activity of 2-[2-[(aminoalkyl)oxy]-5-methoxyphenyl]-3,4-dihydro-4-methyl-3-oxo-2H -1,4-benzothiazines. J Med Chem 1990, 33, 7, 1898-905. |
| 【5】 Otaki, S.; Sato, H.; Ohshima, E.; et al.; Synthesis and antiallergic activity of 11-(aminoalkylidene)-6,11-dihydrodibenz[b,e]oxepin derivatives. J Med Chem 1992, 35, 11, 2074. |
| 【6】 Prous, J.; Castaner, J.; Graul, A.; KW-4679. Drugs Fut 1993, 18, 9, 794. |
| 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) | 12575 | sodium 4-(2-methoxy-2-oxoethyl)benzenolate | C9H9NaO3 | 详情 | 详情 | |
| (II) | 12576 | 2-Benzofuran-1(3H)-one; Phthalide; Benzo[b]furan-1(3H)-one; 1(3H)-Isobenzofuranoneisobenzofuran-1-one | 87-41-2 | C8H6O2 | 详情 | 详情 |
| (III) | 12577 | 2-[[4-(2-Methoxy-2-oxoethyl)phenoxy]methyl]benzoic acid | C17H16O5 | 详情 | 详情 | |
| (IV) | 12578 | methyl 2-(11-oxo-6,11-dihydrodibenzo[b,e]oxepin-2-yl)acetate | C17H14O4 | 详情 | 详情 | |
| (V) | 12579 | [3-(Dimethylamino)propyl](triphenyl)phosphonium bromide | C23H27BrNP | 详情 | 详情 | |
| (VI) | 12580 | (3-Bromopropyl)(triphenyl)phosphonium bromide; (3-Bromopropyl)triphenylphosphonium bromide | 3607-17-8 | C21H21Br2P | 详情 | 详情 |
| (VII) | 12581 | 1,3-Dibromopropane | 109-64-8 | C3H6Br2 | 详情 | 详情 |
| (VIII) | 12582 | 1-[11-[(Z)-3-(Dimethylamino)propylidene]dibenzo[b,e]oxepin-2(6H)-yl]acetone | C22H25NO2 | 详情 | 详情 | |
| (IX) | 12583 | 2-[11-[(Z)-3-(Dimethylamino)propylidene]dibenzo[b,e]oxepin-2(6H)-yl]acetic acid | C21H23NO3 | 详情 | 详情 |