【结 构 式】 |
【分子编号】30260 【品名】2-(5-benzoyl-2-[[(4-methylphenyl)sulfonyl]imino]-1-pyridinyl)acetamide 【CA登记号】 |
【 分 子 式 】C21H19N3O4S 【 分 子 量 】409.46568 【元素组成】C 61.6% H 4.68% N 10.26% O 15.63% S 7.83% |
合成路线1
该中间体在本合成路线中的序号:(V)Friedel-Crafts acylation of benzene with 6-chloronicotinyl chloride (I) using AlCl3 afforded ketone (II). Subsequent displacement of the chlorine atom of (II) by means of ethanolic ammonia at 145 C in a pressure reactor led to the aminopyridine (III), which was converted to sulfonamide (IV) by means of tosyl chloride in pyridine. Alkylation of the pyridine N of (IV) with iodoacetamide gave (V), and further cyclization in the presence of trifluoroacetic anhydride produced the imidazopyridine (VI). Phosphonate (VIII) was prepared by treatment of triethyl phosphonoacetate (VII) with methylamine. Horner-Emmons condensation of this phosphonate with ketone (VI) yielded the E-propenamide (IX). Selective iodination of (IX) at position 3 using N-iodosuccinimide furnished iodide (X). This compound was first deprotonated with PhLi, then subjected to a halogen-metal exchange reaction with tert-butyllithium, and the resulting trianion was reacted with isopropyl isopropanethiolsulfonate to give sulfide (XI). Finally, smooth hydrolysis of the trifluoroacetamide group of (XI) employing MeOH-CH2Cl2 in the presence of silica gel provided the title compound.
【1】 Hamdouchi, C.; de Blas, J.; del Prado, M.; Gruber, J.; Heinz, B.A.; Vance, L.; 2-Amino-3-substituted-6-[(E)-1-phenyl-2-(N-methylcarbamoyl)vinyl]imidazo[1,2-a]pyridines as a novel class of inhibitors of human rhinovirus: Stereospecific synthesis and antiviral activity. J Med Chem 1999, 42, 1, 50. |
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) | 30256 | 6-chloronicotinoyl chloride | 58757-38-3 | C6H3Cl2NO | 详情 | 详情 |
(II) | 30257 | (6-chloro-3-pyridinyl)(phenyl)methanone | C12H8ClNO | 详情 | 详情 | |
(III) | 30258 | (6-amino-3-pyridinyl)(phenyl)methanone | C12H10N2O | 详情 | 详情 | |
(IV) | 30259 | N-(5-benzoyl-2-pyridinyl)-4-methylbenzenesulfonamide | C19H16N2O3S | 详情 | 详情 | |
(V) | 30260 | 2-(5-benzoyl-2-[[(4-methylphenyl)sulfonyl]imino]-1-pyridinyl)acetamide | C21H19N3O4S | 详情 | 详情 | |
(VI) | 30261 | N-(6-benzoylimidazo[1,2-a]pyridin-2-yl)-2,2,2-trifluoroacetamide | C16H10F3N3O2 | 详情 | 详情 | |
(VII) | 10019 | Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate | 867-13-0 | C8H17O5P | 详情 | 详情 |
(VIII) | 30262 | diethyl 2-(methylamino)-2-oxoethylphosphonate | C7H16NO4P | 详情 | 详情 | |
(IX) | 30263 | (E)-N-methyl-3-phenyl-3-[2-[(2,2,2-trifluoroacetyl)amino]imidazo[1,2-a]pyridin-6-yl]-2-propenamide | C19H15F3N4O2 | 详情 | 详情 | |
(X) | 30264 | (E)-3-[3-iodo-2-[(2,2,2-trifluoroacetyl)amino]imidazo[1,2-a]pyridin-6-yl]-N-methyl-3-phenyl-2-propenamide | C19H14F3IN4O2 | 详情 | 详情 | |
(XI) | 30265 | (E)-3-[3-(isopropylsulfanyl)-2-[(2,2,2-trifluoroacetyl)amino]imidazo[1,2-a]pyridin-6-yl]-N-methyl-3-phenyl-2-propenamide | C22H21F3N4O2S | 详情 | 详情 |