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【结 构 式】

【药物名称】

【化学名称】2-[2,6-Dichloro-4-[2-[2(R)-hydroxy-2-(4-hydroxyphenyl)-1(S)-methylethylamino]ethyl]phenylamino]acetic acid hydrate

【CA登记号】227467-90-5 (anhydrous)

【 分 子 式 】C19H24Cl2N2O5

【 分 子 量 】431.31953

【开发单位】Kissei (Originator)

【药理作用】RENAL-UROLOGIC DRUGS, Urinary Incontinence Therapy, beta3-Adrenoceptor Agonists

合成路线1

The condensation of 2-(4-aminophenyl)ethanol (I) with ethyl 2-bromoacetate (II) by means of K2CO3 in DMF gives 2-[4-(2-hydroxyethyl)phenylamino]acetic acid ethyl ester (III), which is chlorinated with t-butyl hypochlorite in dichloromethane to yield the 2,6-dichlorophenyl derivative (IV). The bromination of (IV) by means of PPh3 and CBr4 in dichloromethane affords the 2-bromoethyl derivative (V), which is condensed with (1R,2S)-2-amino-1-(4-hydroxyphenyl)-1-propanol (VI) by means of DIEA in hot DMF to provide the ethyl ester precursor (VII). Finally, this compound is hydrolyzed with aq. 1N NaOH to give the target N-phenylglycine derivative.

1 Tanaka, N.; Mukaiyama, H.; Akahane, M.; Miyata, H.; Akahane, S.; Muranaka, H.; Hirabayashi, A.; Tamai, T.; Discovery of novel N-phenylglycine derivatives as potent and selective beta3-adrenoceptor agonists for the treatment of frequent urination and urinary incontinence. J Med Chem 2001, 44, 9, 1436.
2 Sato, M.; Tanaka, N.; Akahane, M.; Tamai, T.; Muranaka, H.; Mukaiyama, H.; Hirabayashi, A. (Kissei Pharmaceutical Co., Ltd.); Phenylaminoalkylcarboxylic acid derivs. and medicinal compsns. containing the same. EP 1043308; WO 9931045 .
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) 14019 p-Aminophenylethanol; 2-(4-Aminophenyl)-1-ethanol 104-10-9 C8H11NO 详情 详情
(II) 16640 Ethyl 2-bromoacetate; Ethyl bromoacetate 105-36-2 C4H7BrO2 详情 详情
(III) 55795 ethyl 2-[4-(2-hydroxyethyl)anilino]acetate C12H17NO3 详情 详情
(IV) 55796 ethyl 2-[2,6-dichloro-4-(2-hydroxyethyl)anilino]acetate C12H15Cl2NO3 详情 详情
(V) 55797 ethyl 2-[4-(2-bromoethyl)-2,6-dichloroanilino]acetate C12H14BrCl2NO2 详情 详情
(VI) 46836 4-[(1R,2S)-2-amino-1-hydroxypropyl]phenol C9H13NO2 详情 详情
(VII) 55798 ethyl 2-[2,6-dichloro-4-(2-{[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)anilino]acetate C21H26Cl2N2O4 详情 详情
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