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【结 构 式】 
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【药物名称】TAK-427 【化学名称】2-[6-[3-[4-(Diphenylmethoxy)piperidin-1-yl]propylamino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionic acid dihydrate 【CA登记号】265671-81-6, 215529-47-8 (anhydrous), 215530-32-8 (monosodium salt) 【 分 子 式 】C31H41N5O5 【 分 子 量 】563.70292 |
【开发单位】Takeda (Originator) 【药理作用】Atopic Dermatitis, Agents for, DERMATOLOGIC DRUGS, Drugs for Allergic Rhinitis, RESPIRATORY DRUGS, Treatment of Upper Respiratory Tract Disorders, Histamine H1 Antagonists |
合成路线1
Imidazopyridazine (III) was prepared by condensation of 3-amino-6-chloropyridazine (I) with ethyl 4-chloroacetoacetate (II) in refluxing ethanol. Alkylation of (III) with iodomethane in the presence of NaH furnished the dimethyl derivative (IV). Alternatively, intermediate (IV) was directly obtained by condensation of 3-amino-6-chloropyridazine (I) with ethyl 4-bromo-2,2-dimethyl-3-oxobutanoate (V) in the presence of disodium phosphate. Reaction of the chloroimidazopyridazine (IV) with 3-[4-(diphenylmethoxy)piperidin-1-yl]propanamine (VI) at 200 C provided adduct (VII). The ethyl ester function of (VII) was finally hydrolyzed to the target carboxylic acid employing NaOH.
| 【1】 Gyoten, M.; Kawano, Y.; Nagaya, H. (Takeda Chemical Industries, Ltd.); Condensed pyridazine derivs., their production and use. EP 0979231; JP 1999310581; JP 1999310582; US 6248740; WO 9849167 . |
| 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) | 43962 | 6-chloro-3-pyridazinamine; 6-chloro-3-pyridazinylamine | 5469-69-2 | C4H4ClN3 | 详情 | 详情 |
| (II) | 23541 | ethyl 4-chloro-3-oxobutanoate；Ethyl 4-chloro-3-oxobutanoate；Ethyl 4-chloroacetoacetate | 638-07-3 | C6H9ClO3 | 详情 | 详情 |
| (III) | 47696 | ethyl 2-(6-chloroimidazo[1,2-b]pyridazin-2-yl)acetate | C10H10ClN3O2 | 详情 | 详情 | |
| (IV) | 47697 | ethyl 2-(6-chloroimidazo[1,2-b]pyridazin-2-yl)-2-methylpropanoate | C12H14ClN3O2 | 详情 | 详情 | |
| (V) | 47698 | ethyl 4-bromo-2,2-dimethyl-3-oxobutanoate | C8H13BrO3 | 详情 | 详情 | |
| (VI) | 47699 | 3-[4-(benzhydryloxy)-1-piperidinyl]-1-propanamine; 3-[4-(benzhydryloxy)-1-piperidinyl]propylamine | C21H28N2O | 详情 | 详情 | |
| (VII) | 47700 | ethyl 2-[6-([3-[4-(benzhydryloxy)-1-piperidinyl]propyl]amino)imidazo[1,2-b]pyridazin-2-yl]-2-methylpropanoate | C33H41N5O3 | 详情 | 详情 |