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【结 构 式】

【药物名称】AQ-RA-741BS, AQ-RA-741

【化学名称】11-[2-[4-[4-(Diethylamino)butyl]-1-piperidinyl]acetyl]-6,11-dihydro-5H-pyrido[2,3-b][1,4]benzodiazepin-6-one

【CA登记号】123548-16-3

【 分 子 式 】C27H37N5O2

【 分 子 量 】463.62824

【开发单位】Boehringer Ingelheim (Originator)

【药理作用】Antiarrhythmic Drugs, CARDIOVASCULAR DRUGS

合成路线1

Synthesis of the intermediate diazepinone (IV) is accomplished by a one-pot synthesis. Condensation of 2-chloro-3-aminopyridine (I) with the anthranilic ester (II) is effected in the presence of potassium tert-butoxide as a catalyst. The resulting anthranilic amide (III) is cyclized under the influence of catalytic amounts of sulfuric acid. Treatment of (IV) with chloroacetylchloride in toluene yields the corresponding choroacetamide (V). The side chain of AQ-RA 741 is prepared starting from 4-picoline, which is alkylated by reaction with 3-(diethylamino)propylchloride in the presence of n-butyllithium. Hydrogenation of (VIII) using platinum dioxide as a catalyst furnishes the diamine (IX), which is coupled with (V) in the presence of catalytic amounts of sodium iodide in acetone leading to AQ-RA 741 as its free base.

1 Eberlein, W.; Engel, W.; Trummlitz, G.; Mihm, G.; Mayer, N.; Doods, H. (Dr. Karl Thomae GmbH); Condensed diazepinones, process for their preparation and medicines containing them. AU 8824122; DE 3735895; EP 0312895; JP 1989230580; US 5175158 .
2 Eberlein, W.; Doods, H.; Wetzel, B.; AQ-RA-741. Drugs Fut 1990, 15, 8, 786.
3 LaMontagne, M.P.; et al.; Tricyclic compounds as selective muscarinic receptor antagonists. 3. Structure-selectivity relationships in a series of cardioselective (M2) antimuscarinics. J Med Chem 1989, 32, 8, 1728-32.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(A) 11296 2-Chloroacetyl chloride; Chloroacetic chloride 79-04-9 C2H2Cl2O 详情 详情
(I) 11160 2-Chloro-3-pyridinamine; 2-Chloro-3-pyridinylamine; 3-Amino-2-chloropyridine; 2-Chloro-3-aminopyridine 6298-19-7 C5H5ClN2 详情 详情
(II) 11161 methyl 2-aminobenzoate; Methyl anthranilate 134-20-3 C8H9NO2 详情 详情
(III) 11162 2-Amino-N-(2-chloro-3-pyridinyl)benzamide C12H10ClN3O 详情 详情
(IV) 11163 5,11-Dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one C12H9N3O 详情 详情
(V) 11164 11-(2-Chloroacetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one C14H10ClN3O2 详情 详情
(VI) 31150 4-methylpyridine 108-89-4 C6H7N 详情 详情
(VII) 31151 N-(3-chloropropyl)-N,N-diethylamine; 3-chloro-N,N-diethyl-1-propanamine C7H16ClN 详情 详情
(VIII) 31152 N,N-diethyl-N-[4-(4-pyridinyl)butyl]amine; N,N-diethyl-4-(4-pyridinyl)-1-butanamine C13H22N2 详情 详情
(IX) 31153 N,N-diethyl-N-[4-(4-piperidinyl)butyl]amine; N,N-diethyl-4-(4-piperidinyl)-1-butanamine C13H28N2 详情 详情
Extended Information