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【结 构 式】 
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【分子编号】24258 【品名】2-(4-chlorophenoxy)acetyl chloride 【CA登记号】4122-68-3 |
【 分 子 式 】C8H6Cl2O2 【 分 子 量 】205.03984 【元素组成】C 46.86% H 2.95% Cl 34.58% O 15.61% |
合成路线1
该中间体在本合成路线中的序号：(I)PM-170 is synthesized by esterification of 4-chlorophenoxyacetic acid chloride (I) and 3-hydroxymethyl-N-methylpiperidine (II) in dry benzene. PM-170 is recrystallized from ethanol.
| 【1】 Massicot, F.; et al.; Antiobesity activity of a new cyclic amino aryloxyacetate in obese rats and mice. Eur J Med Chem - Chim Ther 1985, 20, 559. |
| 【2】 Godfroid, J.J.; Massicot, F.; PM-170. Drugs Fut 1986, 11, 10, 848. |
合成路线2
该中间体在本合成路线中的序号：(IV)Alkylation of (R)-2-methylpiperazine (I) with 4-fluorobenzyl bromide (II) provides 1-(4-fluorobenzyl)-3-methylpiperazine (III). Subsequent acylation of piperazine (III) with (4-chlorophenoxy)acetyl chloride (IV) furnishes the title amide.
| 【1】 Monahan, S.D.; Xu, W.; Morissey, M.M.; Bauman, J.G.; Ng, H.P.; Hesselgesser, J.E.; Liang, M.; Zheng, W.; Islam, I.; May, K.B.; Ghannam, A.F.; Buckman, B.O.; Horuk, R.; Wei, G.P. (Schering AG); Piperazine derivs. and their use as anti-inflammatory agents. US 6207665; WO 9856771 . |
合成路线3
该中间体在本合成路线中的序号：(VII)In an alternative procedure, N-Boc-D-alanine (I) is activated as the mixed anhydride (II) by treatment with isobutyl chloroformate. Coupling of anhydride (II) with N-(4-fluorobenzyl)glycine methyl ester (III) produces dipeptide (IV). Further cleavage of the N-Boc protecting group of (IV) under acidic conditions proceeds with concomitant cyclization to the diketopiperazine (V). This is then reduced by means of LiAlH4 to piperazine (VI). Finally, acylation of piperazine (VI) with (4-chlorophenoxy)acetyl chloride (VII) provides the title compound.
| 【1】 Islam, I.; May, K.; Bauman, J.; et al.; Synthesis and SAR of CCR1-specific non-peptide antagonists. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 334. |
| 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) | 15859 | Boc-D-Alanine; (2R)-2-[(tert-butoxycarbonyl)amino]propionic acid | 7764-95-6 | C8H15NO4 | 详情 | 详情 |
| (II) | 61036 | ®-2-((tert-butoxycarbonyl)amino)propanoic (isobutyl carbonic) anhydride | C13H23NO6 | 详情 | 详情 | |
| (III) | 61037 | methyl 2-[(4-fluorobenzyl)amino]acetate | C10H12FNO2 | 详情 | 详情 | |
| (IV) | 61038 | methyl 2-[{(2R)-2-[(tert-butoxycarbonyl)amino]propanoyl}(4-fluorobenzyl)amino]acetate | C18H25FN2O5 | 详情 | 详情 | |
| (V) | 61039 | (3R)-1-(4-fluorobenzyl)-3-methyl-2,5-piperazinedione | C12H13FN2O2 | 详情 | 详情 | |
| (VI) | 61035 | (3R)-1-(4-fluorobenzyl)-3-methylpiperazine | C12H17FN2 | 详情 | 详情 | |
| (VII) | 24258 | 2-(4-chlorophenoxy)acetyl chloride | 4122-68-3 | C8H6Cl2O2 | 详情 | 详情 |