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【结 构 式】 
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【分子编号】22186 【品名】(S)-(+)-1-Amino-2-propanol; (2S)-1-amino-2-propanol 【CA登记号】2799-17-9 |
【 分 子 式 】C3H9NO 【 分 子 量 】75.1106 【元素组成】C 47.97% H 12.08% N 18.65% O 21.3% |
合成路线1
该中间体在本合成路线中的序号：(II)By condensation of 2,2'-dithiobis(benzoylchloride) (I) with 2-hydroxypropylamine (II) in dioxane.
| 【1】 Naruse, M.; Niino, H.; Yamada, K.; Murayama, Y.; Hashimoto, T. (Kyowa Hakko Kogyo Co., Ltd.); Antithrombotic pharmaceutical preparation containing 2,2'-dithiobis benzamide derivs. and new 2,2'-dithiobis benzamide derivs.. EP 0006227 . |
| 【2】 Grau, M.; KF-4939. Drugs Fut 1983, 8, 10, 857. |
合成路线2
该中间体在本合成路线中的序号：(III)Amino acid (II) (obtained by N-alkylation of N-Boc-D-phenylalanine (I) with MeI), was coupled to (S)-1-amino-2-propanol (III) using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-HCl (EDC) and 1-hydroxybenzotriazole to give amide (IV). The N-Boc group of (IV) was then deprotected with trifluoroacetic acid in CH2Cl2 to afford (V). Further coupling of (V) with D-naphthylalanine derivative (VI), followed by Boc deprotection with trifluoroacetic acid, provided dipeptide amide (VII). This dipeptide was coupled to intermediate amino acid (VIII) using EDC and 1-hydroxy-7-azabenzotriazole yielding tripeptide (IX). Finally, trifluoroacetic acid-promoted Boc-deprotection of (IX) provided the target compound. Intermediate amino acid (VIII) was prepared from 3-(tert-butoxycarbonylamino)-3-methylbutanoic acid (X) upon conversion to the mixed anhydride with ethyl chloroformate, followed by reduction to alcohol (XI) with LiBH4. Subsequent Swern oxidation of the alcohol (XI) furnished aldehyde (XII). This was condensed with triethyl phosphonoacetate, and then saponified with LiOH to produce the intermediate (VIII).
| 【1】 Hansen, T.K.; Ankersen, M.; Hansen, B.S.; Raun, K.; Nielsen, K.K.; Lau, J.; Peschke, B.; Lundt, B.F.; Thogersen, H.; Johansen, N.L.; Madsen, K.; Andersen, P.H.; Novel orally active growth hormone secretagogues. J Med Chem 1998, 41, 19, 3705. |
| 【2】 Eriksen, E.F.; Kappelgaard, A.-M. (Novo Nordisk A/S); Growth hormone component and bone anti-resorptive agent in cyclic (coherence) treatment of osteoporosis. WO 9746252 . |
| 【3】 Hansen, T.K.; Peschke, B.; Lau, J.; Lundt, B.F.; Ankersen, M.; Watson, B.; Madsen, K. (Novo Nordisk A/S); Cpds. with growth hormone releasing properties. JP 1999209336; JP 1999501054; JP 2000143613; US 6127391; WO 9723508 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10019 | Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate | 867-13-0 | C8H17O5P | 详情 | 详情 | |
| (I) | 22184 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropionic acid | C14H19NO4 | 详情 | 详情 | |
| (II) | 22185 | (2R)-2-[(tert-butoxycarbonyl)(methyl)amino]-3-phenylpropionic acid | 37553-65-4 | C15H21NO4 | 详情 | 详情 |
| (III) | 22186 | (S)-(+)-1-Amino-2-propanol; (2S)-1-amino-2-propanol | 2799-17-9 | C3H9NO | 详情 | 详情 |
| (IV) | 22187 | tert-butyl (1R)-1-benzyl-2-[[(2S)-2-hydroxypropyl]amino]-2-oxoethyl(methyl)carbamate | C18H28N2O4 | 详情 | 详情 | |
| (V) | 22188 | (2R)-N-[(2S)-2-hydroxypropyl]-2-(methylamino)-3-phenylpropanamide | C13H20N2O2 | 详情 | 详情 | |
| (VI) | 22189 | (2R)-2-[(tert-butoxycarbonyl)(methyl)amino]-3-(2-naphthyl)propionic acid | 147577-61-5 | C19H23NO4 | 详情 | 详情 |
| (VII) | 22190 | (2R)-N-((1R)-1-benzyl-2-[[(2S)-2-hydroxypropyl]amino]-2-oxoethyl)-N-methyl-2-(methylamino)-3-(2-naphthyl)propanamide | C27H33N3O3 | 详情 | 详情 | |
| (VIII) | 22191 | (E)-5-[(tert-butoxycarbonyl)amino]-5-methyl-2-hexenoic acid | C12H21NO4 | 详情 | 详情 | |
| (IX) | 22192 | tert-butyl (E)-5-[[(1R)-2-[((1R)-1-benzyl-2-[[(2S)-2-hydroxypropyl]amino]-2-oxoethyl)(methyl)amino]-1-(2-naphthylmethyl)-2-oxoethyl](methyl)amino]-1,1-dimethyl-5-oxo-3-pentenylcarbamate | C39H52N4O6 | 详情 | 详情 | |
| (X) | 22193 | 3-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid | C10H19NO4 | 详情 | 详情 | |
| (XI) | 22194 | tert-butyl 3-hydroxy-1,1-dimethylpropylcarbamate | C10H21NO3 | 详情 | 详情 | |
| (XII) | 22195 | tert-butyl 1,1-dimethyl-3-oxopropylcarbamate | C10H19NO3 | 详情 | 详情 |