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【结 构 式】 
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【分子编号】55687 【品名】(2S)-3-(isopropylamino)-1,2-propanediol 【CA登记号】 |
【 分 子 式 】C6H15NO2 【 分 子 量 】133.19064 【元素组成】C 54.11% H 11.35% N 10.52% O 24.02% |
合成路线1
该中间体在本合成路线中的序号：(IV)The 3-(isopropylamino)propane-1,2(S)-diol (IV) intermediate has been obtained by two different methods: 1. The oxidation of 1,2,5,6-O-diisopropylidene-D-mannitol (I) with Pb(OAc)4 in THF gives (R)-2,3-O-isopropylideglyceraldehyde (II), which is reductocondensed with isopropylamine by means of H2 over Pd/C in methanol to yield (S)-3-(isopropylamino)-1,2-O-isopropylidenepropane-1,2-diol (III). The cleavage of the isopropylidene protecting group of (III) in hot 6N HCl affords the desired 3-(isopropylamino)propane-1,2-diol (IV) intermediate. 2. The reductocondensation of (R)-glyceraldehyde (V) with isopropylamine by means of H2 over Pd/C in methanol gives the desired 3-(isopropylamino)propane-1,2-diol (IV) intermediate. The cyclization of (IV) with benzaldehyde (VI) by heating at 150 C gives the oxazolidine (VII), which is treated with Ts-Cl and K2CO3 in pyridine to yield the tosylate (VIII). Finally, this compound is condensed with 4-[2-(cyclopropylmethoxy)ethyl]phenol (IX) by means of NaH in DMF and hydrolyzed with conc. aq. HCl to provide the target isopropanol derivative.
| 【1】 Baldwin, J.J.; et al.; J Med Chem 1979, 22, 11, 1284. |
| 【2】 Weinstock, L.M.; et al.; J Org Chem 1976, 41, 19, 3121. |
| 【3】 Manoury, P.; Binet, J. (Sanofi-Synthelabo); S isomer of betaxolol, its preparation and its application in therapy. GB 2130585 . |
| 【4】 Manoury, P.M.; et al.; Synthesis of a series of compounds related to betaxolol, a new beta1-adrenoceptor antagonist with a pharmacological and pharmacokinetic profile optimized for the treatment of chronic cardiovascular diseases. J Med Chem 1987, 30, 6, 1003-11. |
| 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) | 45944 | (1S,2S)-1,2-bis[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-1,2-ethanediol | 1707-77-3 | C12H22O6 | 详情 | 详情 |
| (II) | 36759 | (4R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde | 15186-48-8 | C6H10O3 | 详情 | 详情 |
| (III) | 55685 | N-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-N-isopropylamine; N-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-2-propanamine | C9H19NO2 | 详情 | 详情 | |
| (IV) | 55687 | (2S)-3-(isopropylamino)-1,2-propanediol | C6H15NO2 | 详情 | 详情 | |
| (V) | 55686 | (R)-(+)-2,3-Dihydroxypropanal; D-(+)-Glyceraldehyde; D-Glyceraldehyde | 453-17-8 | C3H6O3 | 详情 | 详情 |
| (VI) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
| (VII) | 55688 | [(5S)-3-isopropyl-2-phenyl-1,3-oxazolidin-5-yl]methanol | C13H19NO2 | 详情 | 详情 | |
| (VIII) | 55689 | [(5S)-3-isopropyl-2-phenyl-1,3-oxazolidin-5-yl]methyl 4-methylbenzenesulfonate | C20H25NO4S | 详情 | 详情 | |
| (IX) | 33330 | 4-[2-(Cyclopropylmethoxy)ethyl]phenol; p-(Cyclopropylmethoxyethyl)phenol | C12H16O2 | 详情 | 详情 |