【结 构 式】 |
【分子编号】69012 【品名】1-(2-ethoxyethyl)-2-(4-piperidyl)benzimidazole;1-(2-ethoxyethyl)-2-(piperidin-4-yl)-1H-benzo[d]imidazole 【CA登记号】 |
【 分 子 式 】C16H23N3O 【 分 子 量 】273.37824 【元素组成】C 70.3% H 8.48% N 15.37% O 5.85% |
合成路线1
该中间体在本合成路线中的序号:(X)Oxazoline intermediate (V) can also be prepared by condensation of ethyl 2-[4-(2-hydroxyethyl)phenyl]-2-methylpropionate (VII) with 2-amino-2-methyl-1-propanol (VIII) by means of t-BuOK in CH2Cl2, followed by cyclization with SOCl2 in acetonitrile to give the oxazoline (IX), which is then condensed with 1-(2-ethoxyethyl)-2-(4-piperidyl)benzimidazole (X) in the presence of Na2CO3 in refluxing MeOH .
【1】 Lee, C.-H., Khoo, J.-H., Kwon, K.-C., Ju, H. (Yuhan Corp.). Process for preparation of 2-methyl-2’-phenylpropionic acid derivatives and novel intermediate compounds. WO 2009102155. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(V) | 54968 | 2-[2-(1-{4-[1-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-1-methylethyl]phenethyl}-4-piperidinyl)-1H-benzimidazol-1-yl]ethyl ethyl ether; 2-(1-{4-[1-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-1-methylethyl]phenethyl}-4-piperidinyl)-1-(2-ethoxyethyl)-1H-benzimidazole | C32H44N4O2 | 详情 | 详情 | |
(VII) | 69010 | ethyl 2-[4-(2-hydroxyethyl)phenyl]-2-methylpropionate | C14H20O3 | 详情 | 详情 | |
(VIII) | 21513 | 2-amino-2-methyl-1-propanol;Karl Fischer;2-Amino-2-methyl-propan-1-ol;2-amino-2-methyl-1-propanol | 124-68-5 | C4H11NO | 详情 | 详情 |
(IX) | 69011 | 2-(2-(4-(2-chloroethyl)phenyl)propan-2-yl)-4,4-dimethyl-4,5-dihydrooxazole | C16H22ClNO | 详情 | 详情 | |
(X) | 69012 | 1-(2-ethoxyethyl)-2-(4-piperidyl)benzimidazole;1-(2-ethoxyethyl)-2-(piperidin-4-yl)-1H-benzo[d]imidazole | C16H23N3O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(X)Protection of 2-(4-piperidinyl)benzimidazole (I) with Boc2O in MeOH yields the N-Boc derivative (XI), which is then alkylated with 2-ethoxyethyl mesylate (XII) by means of KOH in toluene to afford the 1-(2-ethoxyethyl)benzimidazole (XIII). After deprotection of intermediate (XIII) with HCl in H2O, the resulting 1-(2-ethoxyethyl)-2-(4-piperidinyl)benzimidazole (X) is alkylated with mesylate (XIV) by means of Na2CO3 in refluxing MeOH, giving the ethyl ester (VIa).
Condensation of mesylate (XV) with 2-(4-piperidinyl)benzimidazole (I) by means of Na2CO3 in refluxing MeOH yields adduct (XVI), which is further alkylated with 2-ethoxyethyl mesylate (XII) in the presence of t-BuOK in DMF at 50 °C to afford the methyl ester (VIb) .
【1】 Lee, C.-H., Khoo, J.-H., Kwon, K.-C., Ju, H. (Yuhan Corp.). Process for preparation of 2-methyl-2’-phenylpropionic acid derivatives and novel intermediate compounds. WO 2009102155. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VIa) | 69008 | ethyl 2-(4-(2-(4-(1-(2-ethoxyethyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)ethyl)phenyl)-2-methylpropanoate | C30H41N3O3 | 详情 | 详情 | |
(VIb) | 69009 | methyl 2-(4-(2-(4-(1-(2-ethoxyethyl)-1H-benzo[d]imidazol-2-yl)piperidin-1-yl)ethyl)phenyl)-2-methylpropanoate | C29H39N3O3 | 详情 | 详情 | |
(I) | 54965 | 2-(4-piperidinyl)-1H-benzimidazole;2-(Piperidin-4-yl)benzimidazole;4-(Benzimidazol-2-yl)piperidine;2-Piperidin-4-yl-1H-benzimidazole | 38385-95-4 | C12H15N3 | 详情 | 详情 |
(X) | 69012 | 1-(2-ethoxyethyl)-2-(4-piperidyl)benzimidazole;1-(2-ethoxyethyl)-2-(piperidin-4-yl)-1H-benzo[d]imidazole | C16H23N3O | 详情 | 详情 | |
(XI) | 69013 | tert-butyl 4-(1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate | C17H23N3O2 | 详情 | 详情 | |
(XII) | 69014 | 2-ethoxyethyl mesylate;2-ethoxyethyl methanesulfonate | C5H12O4S | 详情 | 详情 | |
(XIII) | 69015 | tert-butyl 4-(1-(2-ethoxyethyl)-1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate | C21H31N3O3 | 详情 | 详情 | |
(XIV) | 69016 | ethyl 2-methyl-2-(4-(2-((methylsulfonyl)oxy)ethyl)phenyl)propanoate | C15H22O5S | 详情 | 详情 | |
(XV) | 69018 | methyl 2-methyl-2-(4-(2-((methylsulfonyl)oxy)ethyl)phenyl)propanoate | C14H20O5S | 详情 | 详情 | |
(XVI) | 69017 | methyl 2-(4-(2-(4-(1H-benzo[d]imidazol-2-yl)piperidin-1-yl)ethyl)phenyl)-2-methylpropanoate | C25H31N3O2 | 详情 | 详情 |