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【结 构 式】 
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【分子编号】33601 【品名】(E)-3-(3,4-dimethoxyphenyl)-2-propenoyl chloride 【CA登记号】 |
【 分 子 式 】C11H11ClO3 【 分 子 量 】226.65924 【元素组成】C 58.29% H 4.89% Cl 15.64% O 21.18% |
合成路线1
该中间体在本合成路线中的序号：(II)By condensation of anthranilic acid (o-aminobenzoic acid) (I) with 3,4-dimethoxycinnamoyl chloride (II) by means of pyridine in refluxing chloroform.
| 【1】 Harita, K.; et al.; Aromatic carboxylic amide derivatives. DE 2402398; FR 2214476; GB 1446141; JP 49093335; US 3940422 . |
| 【2】 Hillier, K.; Castaner, J.; N-5'. Drugs Fut 1977, 2, 1, 42. |
合成路线2
该中间体在本合成路线中的序号：(V)The reaction of S-methylisothiourea (I) with Boc2O by means of NaHCO3 gives the N-Boc protected isothiourea (II), which is condensed with 1,4-butanediamine (III) in hot THF to yield the guanidine derivative (IV). The acylation of the amino group of (IV) with 3,4-dimethoxycinnamoyl chloride (V) with THF/DMF affords the corresponding amide (VI), which is deprotected with TFA to provide N-(4-guanidinobutyl)-3,4-dimethoxycinnamamide (VII). Finally, the guanidino group of (VII) is alkylated with 3-methyl-2-butenyl bromide (VIII) catalyzed by DMAP in THF to provide the target, caracasanamide.
| 【1】 Delle Monache, G.; Delle Monache, F.; Botta, B.; Bonnevaux Castillo, S.; Espinal, R.; De Luca, C.; Carmignani, M. (Consiglio Nazionale delle Ricerche); Guanidine derivs. having hypotensive activity, compsn. containing them, and process for obtaining them. EP 0330629; JP 1990003661; US 5059624 . |
| 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) | 10272 | [[Amino(imino)methyl]sulfanyl]methane | 2986-19-8 | C2H6N2S | 详情 | 详情 |
| (II) | 22345 | tert-butyl (E)-[(tert-butoxycarbonyl)amino](methylsulfanyl)methylidenecarbamate | C12H22N2O4S | 详情 | 详情 | |
| (III) | 42070 | 1,4-butanediamine; 4-aminobutylamine | 110-60-1 | C4H12N2 | 详情 | 详情 |
| (IV) | 53109 | tert-butyl (Z)-[(4-aminobutyl)amino][(tert-butoxycarbonyl)amino]methylidenecarbamate | n/a | C15H30N4O4 | 详情 | 详情 |
| (V) | 33601 | (E)-3-(3,4-dimethoxyphenyl)-2-propenoyl chloride | C11H11ClO3 | 详情 | 详情 | |
| (VI) | 53110 | tert-butyl (Z)-[(tert-butoxycarbonyl)amino][(4-{[(E)-3-(3,4-dimethoxyphenyl)-2-propenoyl]amino}butyl)amino]methylidenecarbamate | n/a | C26H40N4O7 | 详情 | 详情 |
| (VII) | 53111 | (E)-N-(4-{[amino(imino)methyl]amino}butyl)-3-(3,4-dimethoxyphenyl)-2-propenamide | n/a | C16H24N4O3 | 详情 | 详情 |
| (VIII) | 12989 | 4-Bromo-2-methyl-2-butene; 1-Bromo-3-methyl-2-butene | 870-63-3 | C5H9Br | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(VI)Cyclization of N,N'-diethylurea (I) with cyanoacetic acid (II) in hot acetic anhydride gives 6-amino-1,3-diethyluracil (III) which is nitrosated with NaNO2/HOAc in water to yield 6-amino-1,3-diethyl-5-nitrosouracil (IV). The reduction of (IV) with Na2S2O4 and K2CO3 in concentrated aqueous ammonia affords 5,6-diamino-1,3-diethyluracil (V), which is condensed with either 3-(3,4-dimethoxyphenyl)-2(E)-propenoyl chloride (VI) in EtOH/water or 3-(3,4-dimethoxyphenyl)-2(E)-propenoic acid (VII) and 3-[3-(diethylamino)propyl]-1-ethylcarbodiimide (EDAC) in dioxane/water to provide the corresponding amide (VIII). Cyclization of (VIII) by means of NaOH in the same solvent furnishes the xanthine derivative (IX), which is finally methylated with methyl iodide and K2CO3 in DMF.
| 【1】 Blicke, F.F.; Godt, H.C. Jr.; Reactions of 1,3-dimethyl-5,6-diaminouracil. J Am Chem Soc 1954, 76, 2798. |
| 【2】 Leeson, P.A.; Castañer, J.; Sorbera, L.A.; Martín, L.; Rabasseda, X.; KW-6002. Drugs Fut 2001, 26, 1, 21. |
| 【3】 Shimada, J.; Koike, N.; Nonaka, H.; et al.; Adenosine A2A antagonists with potent anti-cataleptic activity. Bioorg Med Chem Lett 1997, 7, 18, 2349. |
| 【4】 Suzuki, F.; Shimada, J.; Ishii, A.; Nakamura, J.; Ichikawa, S.; Kitamura, S.; Koike, N. (Kyowa Hakko Kogyo Co., Ltd.); Antidepressant. EP 0628311; JP 1994502746; WO 9401114 . |
| 【5】 Suzuki, F.; Shimada, J.; Koike, N.; Nakamura, J.; Shiozaki, S.; Ichikawa, S.; Nonaka, H. (Kyowa Hakko Kogyo Co., Ltd.); Therapeutic agents for Parkinson's disease. EP 0590919; JP 1994211856; US 5484920 . |
| 【6】 Miwa, K.; Ito, K.; Kato, N.; Kuge, Y.; Kousai, M.; Tomioka, S. (Kyowa Hakko Kogyo Co., Ltd.); Preparation of uracil derivs.. JP 1997040652 . |
| 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) | 43818 | N,N'-diethylurea | 623-76-7 | C5H12N2O | 详情 | 详情 |
| (II) | 12591 | Cyanoacetic Acid; 2-Cyanoacetic acid | 372-09-8 | C3H3NO2 | 详情 | 详情 |
| (III) | 43819 | 6-amino-1,3-diethyl-2,4(1H,3H)-pyrimidinedione | C8H13N3O2 | 详情 | 详情 | |
| (IV) | 43820 | 6-amino-1,3-diethyl-5-nitroso-2,4(1H,3H)-pyrimidinedione | C8H12N4O3 | 详情 | 详情 | |
| (V) | 28567 | 5,6-diamino-1,3-diethyl-2,4(1H,3H)-pyrimidinedione | C8H14N4O2 | 详情 | 详情 | |
| (VI) | 33601 | (E)-3-(3,4-dimethoxyphenyl)-2-propenoyl chloride | C11H11ClO3 | 详情 | 详情 | |
| (VII) | 28568 | (E)-3-(3,4-dimethoxyphenyl)-2-propenoic acid | 2316-26-9 | C11H12O4 | 详情 | 详情 |
| (VIII) | 43821 | (E)-N-(6-amino-1,3-diethyl-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl)-3-(3,4-dimethoxyphenyl)-2-propenamide | C19H24N4O5 | 详情 | 详情 | |
| (IX) | 28569 | 8-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-1,3-diethyl-3,7-dihydro-1H-purine-2,6-dione | C19H22N4O4 | 详情 | 详情 |