【结 构 式】 |
【药物名称】Evatanepag,CP-533536 【化学名称】2-[3-[N-(4-tert-Butylbenzyl)-N-(pyridin-3-ylsulfonyl)aminomethyl]phenoxy]acetic acid 【CA登记号】223488-57-1, 223490-49-1 (Na salt) 【 分 子 式 】C25H28N2O5S 【 分 子 量 】468.57631 |
【开发单位】Pfizer (Originator), Atrix (Formulation) 【药理作用】Bone Diseases, Treatment of, Bone Formation Stimulants, METABOLIC DRUGS, Treatment of Osteoporosis, Prostanoid EP2 Agonists |
合成路线1
Alkylation of 3-hydroxybenzaldehyde (I) with t-butyl bromoacetate (II) affords t butyl (3-formylphenoxy)acetate (III). Aldehyde (III) is then converted to oxime (IV) upon treatment with hydroxylamine in MeOH. Reduction of oxime (IV) to the benzylic amine (V) is carried out by catalytic hydrogenation in the presence of Raney nickel. Subsequent reductive alkylation of amine (V) with 4-t-butylbenzaldehyde (VI) furnishes the secondary amine (VII). This is then acylated by pyridine-3-sulfonyl chloride (VIII) producing sulfonamide (IX). The t-butyl ester group of (IX) is finally cleaved with trifluoroacetic acid to give the corresponding carboxylic acid.
【1】 Rosati, R.L.; Lefker, B.A.; Cameron, K.O. (Pfizer Inc.); Prostaglandin agonists and their use to treat bone disorders. EP 1021410; JP 2001519414; US 6498172; WO 9919300 . |
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) | 28537 | 3-hydroxybenzaldehyde | 100-83-4 | C7H6O2 | 详情 | 详情 |
(II) | 17430 | 2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate | 5292-43-3 | C6H11BrO2 | 详情 | 详情 |
(III) | 64442 | tert-butyl 2-(3-formylphenoxy)acetate | C13H16O4 | 详情 | 详情 | |
(IV) | 64443 | tert-butyl 2-{3-[(hydroxyimino)methyl]phenoxy}acetate | C13H17NO4 | 详情 | 详情 | |
(V) | 64444 | tert-butyl 2-[3-(aminomethyl)phenoxy]acetate | C13H19NO3 | 详情 | 详情 | |
(VI) | 16638 | 4-(tert-butyl)benzaldehyde; 4-tert-Butyl-benzaldehyde | 939-97-9 | C11H14O | 详情 | 详情 |
(VII) | 64445 | tert-butyl 2-[3-({[4-(tert-butyl)benzyl]amino}methyl)phenoxy]acetate | C24H33NO3 | 详情 | 详情 | |
(VIII) | 64446 | 3-pyridinesulfonyl chloride | C5H4ClNO2S | 详情 | 详情 | |
(IX) | 64447 | tert-butyl 2-(3-{[[4-(tert-butyl)benzyl](3-pyridinylsulfonyl)amino]methyl}phenoxy)acetate | C29H36N2O5S | 详情 | 详情 |