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【结 构 式】 
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【分子编号】59224 【品名】3-(3-Aminophenyl)propionic acid; beta-Aminohydrocinnamic acid; DL-3-Amino-3-phenylpropionic acid; 3-Amino-3-phenylpropionic acid 【CA登记号】614-19-7 |
【 分 子 式 】C9H11NO2 【 分 子 量 】165.19188 【元素组成】C 65.44% H 6.71% N 8.48% O 19.37% |
合成路线1
该中间体在本合成路线中的序号：(III)In the original synthesis of the title compound, Knoevenagel condensation of benzaldehyde (I) with malonic acid (II) in the presence of ammonium acetate produced the beta-aminoacid (III). Reductive alkylation of the amino group of (III) with formaldehyde produced the dimethyl amine (IV). Then, Fischer esterification of (IV) with ethanolic HCl furnished the intermediate amino ester (V). Amino ester (V) was alternatively obtained by Michael addition of dimethylamine to ethyl cinnamate (VI). Reduction of the ester function of (V) provided amino alcohol (VII). The sodium alkoxide of (VII) was then coupled with 1-fluoronaphthalene (VIII) to produce the racemic amino ether, which was finally resolved into enantiomers by means of tartaric acid.
| 【1】 Robertson, D.W.; Thompson, D.C.; Wong, D.T. (Eli Lilly and Company); 1-Phenyl-3-naphthalenyloxypropanamines. AU 8814335; EP 0288188; JP 1988258837; US 5135947 . |
| 【2】 Wheeler, W.J.; O'Bannon, D.D.; A chiral synthesis of dapoxetine hydrochloride, a serotonin reuptake inhibitor, and its 14C isotopomer. J Label Compd Radiopharm 1992, 31, 4, 305. |
| 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) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
| (II) | 12963 | Malonic acid | 141-82-2 | C3H4O4 | 详情 | 详情 |
| (III) | 59224 | 3-(3-Aminophenyl)propionic acid; beta-Aminohydrocinnamic acid; DL-3-Amino-3-phenylpropionic acid; 3-Amino-3-phenylpropionic acid | 614-19-7 | C9H11NO2 | 详情 | 详情 |
| (IV) | 59221 | N,N-dimethyl-3-phenyl-beta-alanine | C11H15NO2 | 详情 | 详情 | |
| (V) | 59222 | ethyl 3-(dimethylamino)-3-phenylpropanoate | C13H19NO2 | 详情 | 详情 | |
| (VI) | 54905 | Cinnamic acid ethylester; Ethyl cinnamate | C11H12O2 | 详情 | 详情 | |
| (VII) | 59223 | 3-(dimethylamino)-3-phenyl-1-propanol | C11H17NO | 详情 | 详情 | |
| (VIII) | 40503 | 1-fluoronaphthalene | 321-38-0 | C10H7F | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)
| 【1】 Haycock-Lewandowski SJ, Wilder A, Ahman J. 2008. Development of a bulk enabling route to maraviroc (UK-427, 857), a CCR-5 receptor antagonist. Organic Process Research & Development, 12(6): 1094～1103. |
| 【2】 Tung R. 2008. Preparation of deuterated triazolyl tropane derivatives as CCR5 receptor inhibitors. WO 2008063600. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 67255 | (S)-methyl 3-amino-3-phenylpropanoate (2R,3S)-2,3-dihydroxysuccinate | C14H19NO8 | 详情 | 详情 | |
| (I) | 67247 | 8-benzyl-8-azabicyclo[3.2.1]octan-3-one | 28957-72-4 | C14H17NO | 详情 | 详情 |
| (II) | 67248 | 8-benzyl-8-azabicyclo[3.2.1]octan-3-one oxime | 76272-34-9 | C14H18N2O | 详情 | 详情 |
| (III) | 67249 | 8-benzyl-8-azabicyclo[3.2.1]octan-3-amine | C14H20N2 | 详情 | 详情 | |
| (IV) | 67251 | N-(8-benzyl-8-azabicyclo[3.2.1]octan-3-yl)isobutyramide | 376348-67-3 | C18H26N2O | 详情 | 详情 |
| (V) | 67252 | 8-benzyl-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octane | C20H28N4 | 详情 | 详情 | |
| (VI) | 10498 | Benzaldehyde;Benzoic aldehyde;Phenylmethanal | 100-52-7 | C7H6O | 详情 | 详情 |
| (VII) | 67253 | 3-(2-isopropyl-5-methyl-1H-pyrrol-1-yl)-8-azabicyclo[3.2.1]octane | C15H24N2 | 详情 | 详情 | |
| (VIII) | 12963 | Malonic acid | 141-82-2 | C3H4O4 | 详情 | 详情 |
| (IX) | 59224 | 3-(3-Aminophenyl)propionic acid; beta-Aminohydrocinnamic acid; DL-3-Amino-3-phenylpropionic acid; 3-Amino-3-phenylpropionic acid | 614-19-7 | C9H11NO2 | 详情 | 详情 |
| (X) | 67254 | methyl 3-amino-3-phenylpropanoate | C10H13NO2 | 详情 | 详情 | |
| (XII) | 67256 | (S)-methyl 3-(((benzyloxy)carbonyl)amino)-3-phenylpropanoate | C18H19NO4 | 详情 | 详情 | |
| (XIII) | 67257 | (S)-3-(((benzyloxy)carbonyl)amino)-3-phenylpropanoic acid | C17H17NO4 | 详情 | 详情 | |
| (XIV) | 67258 | (S)-benzyl (3-hydroxy-1-phenylpropyl)carbamate | C17H19NO3 | 详情 | 详情 | |
| (XV) | 67259 | (S)-benzyl (3-oxo-1-phenylpropyl)carbamate | C17H17NO3 | 详情 | 详情 | |
| (XVI) | 67260 | benzyl ((1S)-3-(3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropyl)carbamate | C30H39N5O2 | 详情 | 详情 | |
| (XVII) | 67261 | (1S)-3-(3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropan-1-amine | C22H33N5 | 详情 | 详情 | |
| (XVIII) | 67262 | 4,4-difluorocyclohexanecarbonyl chloride | C7H9ClF2O | 详情 | 详情 | |
| (XX) | 67250 | 8-benzyl-8-azabicyclo[3.2.1]octan-3-amine | C14H20N2 | 详情 | 详情 |