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【结 构 式】 
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【分子编号】63191 【品名】1-(tert-butyl)-1,2,3,6-tetrahydro-4-pyridinyl trifluoromethanesulfonate 【CA登记号】 |
【 分 子 式 】C10H16F3NO3S 【 分 子 量 】287.3031896 【元素组成】C 41.81% H 5.61% F 19.84% N 4.88% O 16.71% S 11.16% |
合成路线1
该中间体在本合成路线中的序号：(XVII)Quaternization of 1-ethyl-4-piperidone (XIV) with methyl iodide provides the ammonium salt (XV) which, upon treatment with tert-butylamine and NaHCO3, gives rise to 1-tert-butyl-4-piperidone (XVI). The reaction of 1-tert-butyl-4-piperidone (XVI) firstly with LiN(SiMe3)2 and subsequently with N-(5-chloro-2-pyridyl) trifluoromethanesulfonimide [(Tf)2NPyr] in THF provides the enol triflate (XVII). Reaction of triflate (XVII) with hexamethylditin in the presence of palladium catalyst furnishes 1-tert-butyl-4-(trimethylstannyl)-1,2,3,6-tetrahydropyridine (XVIII). Stille coupling between the quinazolinyl triflate (XIII) and the stannyl tetrahydropyridine (XVIII) produces adduct (XIX). Finally, hydrogenation of the tetrahydropyridine double bond of (XIX) using PtO2 as the catalyst leads to the target piperidinyl compound.
| 【1】 Stelmach, J.E.; Liu, L.; Patel, S.B.; Pivnichny, J.V.; Scapin, G.; Singh, S.; Hop, C.E.C.A.; Wang, Z.; Strauss, J.R.; Cameron, P.M.; Nichols, E.A.; O'Keefe, S.J.; O'Neill, E.A.; Schmatz, D.M.; Schwartz, C.D.; Thompson, C.M.; Zaller, D.M.; Doherty, J.B.; Design and synthesis of potent, orally bioavailable dihydroquinazolinone inhibitors of p38 MAP kinase. Bioorg Med Chem Lett 2003, 13, 2, 277. |
| 【2】 Doherty, J.B.; Rupprecht, K.M.; Goulet, J.L.; Chen, M.-H.; Bao, J.; Liu, L.; Miao, S.; Hunt, J.A.; Hong, X.; Stelmach, J.E.; Ruzek, R.D.; Wisnoski, D.D.; Natarajan, S.R. (Merck & Co., Inc.); (Halo-benzo carbonyl)heterocyclic fused phenyl p38 kinase inhibiting agents. EP 1345603; WO 0258695 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIII) | 63190 | 5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-2-oxo-1,2,3,4-tetrahydro-7-quinazolinyl trifluoromethanesulfonate | C21H11Cl3F4N2O4S | 详情 | 详情 | |
| (XIV) | 28868 | 1-ethyl-4-piperidinone; N-ethyl-4-piperidinone | 3612-18-8 | C7H13NO | 详情 | 详情 |
| (XV) | 51994 | 1-ethyl-1-methyl-4-oxopiperidinium iodide | C8H16INO | 详情 | 详情 | |
| (XVI) | 24875 | 1-(tert-butyl)-4-piperidinone; N-(tert-butyl)-4-piperidinone | C9H17NO | 详情 | 详情 | |
| (XVII) | 63191 | 1-(tert-butyl)-1,2,3,6-tetrahydro-4-pyridinyl trifluoromethanesulfonate | C10H16F3NO3S | 详情 | 详情 | |
| (XVIII) | 63192 | 1-(tert-butyl)-4-(trimethylstannyl)-1,2,3,6-tetrahydropyridine | C12H25NSn | 详情 | 详情 | |
| (XIX) | 63193 | 7-[1-(tert-butyl)-1,2,3,6-tetrahydro-4-pyridinyl]-5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-3,4-dihydro-2(1H)-quinazolinone | C29H27Cl3FN3O | 详情 | 详情 |