|
【结 构 式】 
|
【分子编号】12417 【品名】methyl 4-(acetamido)-2-methoxybenzoate; Methyl 4-acetamido-2-methoxybenzoate 【CA登记号】4093-28-1 |
【 分 子 式 】C11H13NO4 【 分 子 量 】223.22856 【元素组成】C 59.19% H 5.87% N 6.27% O 28.67% |
合成路线1
该中间体在本合成路线中的序号：(I)Saponification of 4-acetylamino-2-methoxybenzoate methyl ester (I) with NaOH in MeOH provides carboxylic acid (II), which is then coupled to cis-4-amino-1-[3-(fluorophenoxy)propyl]-3-methoxypiperidine (III) by means of ethyl chloroformate and Et3N in chloroform, affording benzamide (IV). Removal of the acetyl group either by means of HCl at reflux or with NaOH in refluxing MeOH furnishes derivative (V), which is finally converted into the desired product by chlorination with N-chlorosuccinimide (NCS) in acetic acid. Alternatively, compound (IV) can be converted into the target compound by first chlorination with NCS in HOAc, providing chloro derivative (VI), followed by acetyl removal either with HCl at 90 C or with NaOH in refluxing MeOH.
| 【1】 Serra i Masia, J.; Montserrat Vidal, C.; Process for obtaining cis-4-amino-5-chloro-N-[1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide. ES 2019011 . |
| 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) | 12417 | methyl 4-(acetamido)-2-methoxybenzoate; Methyl 4-acetamido-2-methoxybenzoate | 4093-28-1 | C11H13NO4 | 详情 | 详情 |
| (II) | 17956 | 4-(acetamido)-2-methoxybenzoic acid | 4093-29-2 | C10H11NO4 | 详情 | 详情 |
| (III) | 49554 | (3S,4R)-1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidinamine; (3S,4R)-1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidinylamine | C15H23FN2O2 | 详情 | 详情 | |
| (IV) | 50814 | 4-(acetamido)-N-[(3S,4R)-1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidinyl]-2-methoxybenzamide | C25H32FN3O5 | 详情 | 详情 | |
| (V) | 50815 | 4-amino-N-[(3S,4R)-1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidinyl]-2-methoxybenzamide | C23H30FN3O4 | 详情 | 详情 | |
| (VI) | 50816 | 4-(acetamido)-5-chloro-N-[(3S,4R)-1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidinyl]-2-methoxybenzamide | C25H31ClFN3O5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)A new synthesis for [14C]-labeled batanopride has been described: The starting material is 4-amino-2-hydroxybenzoic acid labeled with [14C] at the carboxy group (I). The methylation of (I) in the usual way gives 4-amino-2-methoxybenzoic acid methyl ester (II), which is treated with acetic anhydride to yield the corresponding acetamido derivative (III). Chlorination of (III) with Cl2 in acetic acid affords 4-acetamido-5-chloro-2-methoxybenzoic acid methyl ester (IV), which is hydrolyzed with aqueous NaOH to 4-amino-5-chloro-2-methoxybenzoic acid (V). The condensation of (V) with 2-(diethylamino)ethylamine (VI) by means of triethylamine and isobutyl chloroformate in THF gives the corresponding amide (VII), which is demethylated with sodium ethanethiolate in DMF to yield the phenolate (VIII). The condensation of (VIII) with 3-chloro-2-butanone (IX) in DMF affords batanopride free base (X), which is finally treated with HCl in acetone - water.
| 【1】 Standridge, R.T.; Swigor, J.E.; Synthesis of 4-amino-5-chloro-N[2-(diethylamino)ethyl]-2-[(butan-2-on-3-yl)oxy]-[carbonyl-C-14]benzamide hydrochloride (C-14-batanopride). J Label Compd Radiopharm 1991, 29, 9, 983. |
| 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) | 12415 | 4-Aminosalicylic Acid; 4-Amino-2-hydroxybenzoic acid | 65-49-6 | C7H7NO3 | 详情 | 详情 |
| (I) | 45126 | 4-amino-2-hydroxybenzoic acid | C7H7NO3 | 详情 | 详情 | |
| (II) | 12416 | methyl 4-amino-2-methoxybenzoate | 27492-84-8 | C9H11NO3 | 详情 | 详情 |
| (II) | 45127 | methyl 4-amino-2-methoxybenzoate | C9H11NO3 | 详情 | 详情 | |
| (III) | 12417 | methyl 4-(acetamido)-2-methoxybenzoate; Methyl 4-acetamido-2-methoxybenzoate | 4093-28-1 | C11H13NO4 | 详情 | 详情 |
| (III) | 45128 | methyl 4-(acetamido)-2-methoxybenzoate | C11H13NO4 | 详情 | 详情 | |
| (IV) | 12418 | 4-Acetamido-5-chloro-2-methoxy methyl benzoate; methyl 4-(acetamido)-5-chloro-2-methoxybenzoate; Methyl 4-acetamido-5-chloro-2-methoxybenzoate; 4-Acetamido-5-chloro-2-methoxybenzoic acid methyl ester; 4-Acetamido-5-chloro-o-anisic acid methyl ester | 4093-31-6 | C11H12ClNO4 | 详情 | 详情 |
| (IV) | 45129 | methyl 4-(acetamido)-5-chloro-2-methoxybenzoate | C11H12ClNO4 | 详情 | 详情 | |
| (V) | 12419 | 4-Amino-5-chloro-2-methoxybenzoic acid | 7206-70-4 | C8H8ClNO3 | 详情 | 详情 |
| (V) | 45130 | 4-amino-5-chloro-2-methoxybenzoic acid | C8H8ClNO3 | 详情 | 详情 | |
| (VI) | 12420 | N-(2-Aminoethyl)-N,N-diethylamine; N,N-Diethylethylene-diamine; N(1),N(1)-Diethyl-1,2-ethanediamine | 100-36-7 | C6H16N2 | 详情 | 详情 |
| (VII) | 12421 | 4-Amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide | 364-62-5 | C14H22ClN3O2 | 详情 | 详情 |
| (VII) | 45131 | 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide | C14H22ClN3O2 | 详情 | 详情 | |
| (VIII) | 12422 | sodium 5-amino-4-chloro-2-([[2-(diethylamino)ethyl]amino]carbonyl)benzenolate | C13H19ClN3NaO2 | 详情 | 详情 | |
| (VIII) | 45132 | sodium 5-amino-4-chloro-2-([[2-(diethylamino)ethyl]amino]carbonyl)benzenolate | C13H19ClN3NaO2 | 详情 | 详情 | |
| (IX) | 12423 | 3-Chloro-2-butanone | 4091-39-8 | C4H7ClO | 详情 | 详情 |
| (X) | 12424 | 4-Amino-5-chloro-N-[2-(diethylamino)ethyl]-2-(1-methyl-2-oxopropoxy)benzamide | C17H26ClN3O3 | 详情 | 详情 | |
| (X) | 45133 | 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-(1-methyl-2-oxopropoxy)benzamide | C17H26ClN3O3 | 详情 | 详情 |