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【结 构 式】 
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【分子编号】68057 【品名】1-(2-(2-((allyloxy)methyl)-4-nitrophenoxy)ethyl)pyrrolidine 【CA登记号】 |
【 分 子 式 】C16H22N2O4 【 分 子 量 】306.36176 【元素组成】C 62.73% H 7.24% N 9.14% O 20.89% |
合成路线1
该中间体在本合成路线中的序号：(III)condensation of 2-(allyloxymethyl)-1-(2-chloroethoxy)-4-nitrobenzene (VI) with pyrrolidine (XI) in dimethylacetamide at 60 °c affords 1-[2-[2-(allyloxymethyl)-4-nitrophenoxy]ethyl]pyrrolidine (XII), which by reduction with SnCl2 in MeoH/cH2cl2 or with Fe and NH4Cl provides the corresponding aniline (XIII). coupling of amine (XIII) with 4-[3-(allyloxymethyl)phenyl]-2-chloropyrimidine (VIII) In the presence of HCl in BuOH at 100 °c gives the diallyl derivative (XIV), which finally undergoes ring-closing metathesIs In the presence of Grubbs’ second-generation catalyst and TFA in CH2Cl2 at 50 °c or in the presence of the Zhan-1B catalyst .
| 【1】 Lee, A., William, A., Poulsen, A. et al. Design, synthesis and SAR studies leading to SB1518, a novel macrocyclic JAK2/FLT3 inhibitor in phase 2 clinical trials for myelofibrosis and lymphoma. 102nd Annu Meet Am Assoc cancer Res (AAcR) (April 2-6, orlando) 2011, Abst 3564. |
| 【2】 William, A.D., Lee, A.c., blanchard, S. et al. Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma. J Med chem 2011, 54(13): 4638-58. |
| 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) | 68050 | 2-((allyloxy)methyl)-1-(2-chloroethoxy)-4-nitrobenzene | C12H14ClNO4 | 详情 | 详情 | |
| (II) | 11376 | Pyrrolidine | 123-75-1 | C4H9N | 详情 | 详情 |
| (III) | 68057 | 1-(2-(2-((allyloxy)methyl)-4-nitrophenoxy)ethyl)pyrrolidine | C16H22N2O4 | 详情 | 详情 | |
| (IV) | 68058 | 3-((allyloxy)methyl)-4-(2-(pyrrolidin-1-yl)ethoxy)aniline | C16H24N2O2 | 详情 | 详情 | |
| (V) | 68052 | 4-[3-(allyloxymethyl)phenyl]-2-chloropyrimidine | C14H13ClN2O | 详情 | 详情 | |
| (VI) | 68059 | N-(3-((allyloxy)methyl)-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-5-(3-((allyloxy)methyl)phenyl)pyrimidin-2-amine | C30H36N4O3 | 详情 | 详情 |