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【结 构 式】 
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【分子编号】68694 【品名】1-(1-Boc-piperidin-4-yl)-4-bromo-1H-pyrazole;4-(4-Bromopyrazol-1-yl)piperidine-1-carboxylicacid tert-butyl ester 【CA登记号】877399-50-3 |
【 分 子 式 】C13H20BrN3O2 【 分 子 量 】330.225 【元素组成】C 47.28% H 6.10% Br 24.20% N 12.72% O 9.69% |
合成路线1
该中间体在本合成路线中的序号：(VI)Reaction of 5-bromo-3-[1(R)-(2,6-dichloro-3-fluorophenyl)ethyl]-pyridin-2-amine (I) with Boc2O by means of DMAP in DMF gives the protected aniline (II), which is condensed with bis(pinacolato)-diboron (III) by means of a Pd catalyst and KOAc in DMSO to yield the N-protected boronic ester (IV). Deprotection of the amino group of compound (IV) by means of HCl in dioxane/dichloromethane affords the boronic ester (V), which is condensed with 1-(1-Boc-piperidin-4-yl)-4-bromo-1H-pyrazole (VI) by means of PdCl2(PPh3)2 and Na2CO3 in hot DME/water to provide the adduct (VII). Finally, this compound is N-deprotected by means of HCl in dioxane/dichloromethane, as before .
| 【1】 Cui, J.J., Funk, L.A., Jia, L. et al. (Pfizer, Inc.; Agouron Pharmaceuticals, Inc.). Enantiomerically pure aminoheteroaryl compounds as protein kinase inhibitors. EP 1786785, JP 2008510790, US 2006046991, WO 2006021884. |
| 【2】 Cui, J.J., Funk, L.A., Jia, L. et al. (Pfizer, Inc.). Pyrazole-substituted aminoheteroaryl compounds as protein kinase inhibitors. EP 1784396, JP 2008510788, WO 2006021881. |
| 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) | 68698 | 5-bromo-3-[1(R)-(2,6-dichloro-3-fluorophenyl)ethyl]-pyridin-2-amine;(R)-5-bromo-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine | C13H10BrCl2FN2O | 详情 | 详情 | |
| (II) | 68697 | C23H26BrCl2FN2O5 | 详情 | 详情 | ||
| (III) | 53342 | 4,4,4',4',5,5,5',5'-Octamethyl-2,2'-bi-1,3,2-dioxaborolane; Bis(pinacolato)diboron; Diboron pinacol ester | 73183-34-3 | C12H24B2O4 | 详情 | 详情 |
| (IV) | 68696 | C29H38BCl2FN2O7 | 详情 | 详情 | ||
| (V) | 68695 | (R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine | C19H22BCl2FN2O3 | 详情 | 详情 | |
| (VI) | 68694 | 1-(1-Boc-piperidin-4-yl)-4-bromo-1H-pyrazole;4-(4-Bromopyrazol-1-yl)piperidine-1-carboxylicacid tert-butyl ester | 877399-50-3 | C13H20BrN3O2 | 详情 | 详情 |
| (VII) | 68693 | (R)-tert-butyl 4-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate | C26H30Cl2FN5O3 | 详情 | 详情 |