【结 构 式】 |
【分子编号】22853 【品名】Arginine; 2-Amino-5-guanidinopentanoic acid 【CA登记号】 |
【 分 子 式 】C6H14N4O2 【 分 子 量 】174.20292 【元素组成】C 41.37% H 8.1% N 32.16% O 18.37% |
合成路线1
该中间体在本合成路线中的序号:(IX)The reaction of 4,6-dichloropyrimidin-5-amine (I) with 5-aminopentanol (I) gives 4-chloro-6-(5-hydroxypentylamino)pyrimidin-5 amine (III), which is cyclized with triethyl orthoformate (IV) yielding 6-chloro-9-(5-hydroxypentyl)purine (V). The hydrolysis of (V) with formic acid affords 9-(5-hydroxypentyl) hypoxanthine (VI), which is treated with phosgene (VII) to give 9-[5-(chlorocarbonyloxy)pentyl]hypoxanthine (VIII). Finally, this compound is condensed with arginine (IX).
【1】 Stradi, R.; Cornaglia-Ferraris, P.; Perezzani, L.S.; Forni, G.; Riccardi, C.; PCF-39. Drugs Fut 1987, 12, 2, 134. |
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) | 22845 | 5-Amino-4,6-dichloropyrimidine; 4,6-dichloro-5-pyrimidinylamine; 4,6-dichloro-5-pyrimidinamine | 5413-85-4 | C4H3Cl2N3 | 详情 | 详情 |
(II) | 22846 | 5-amino-1-pentanol | 2508-29-4 | C5H13NO | 详情 | 详情 |
(III) | 22847 | 5-[(5-amino-6-chloro-4-pyrimidinyl)amino]-1-pentanol | C9H15ClN4O | 详情 | 详情 | |
(IV) | 21304 | Triethyl orthoformate; 1-(Diethoxymethoxy)ethane; Diethoxymethyl ethyl ether | 122-51-0 | C7H16O3 | 详情 | 详情 |
(V) | 22849 | 5-(6-chloro-9H-purin-9-yl)-1-pentanol | C10H13ClN4O | 详情 | 详情 | |
(VI) | 22850 | 9-(5-hydroxypentyl)-9H-purin-6-ol | C10H14N4O2 | 详情 | 详情 | |
(VIII) | 22852 | 9-[5-[(chlorocarbonyl)oxy]pentyl]-6-hydroxy-9H-purine | C11H13ClN4O3 | 详情 | 详情 | |
(IX) | 22853 | Arginine; 2-Amino-5-guanidinopentanoic acid | C6H14N4O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(XIII)Coupling Method 1. Treatment of L-Arginine (XIII) with K2CO3 and assembling to intermediate (VII) affords derivative (XIV). After protection of the piperidine derivative (XV) as its tert-butyl ether (XVI) by means of isobutylene (B) in acidic media, (XVI) is condensed with (XIV) in the presence of Et3N to yield (XVII). Finally, elimination of the protecting groups with TFA, HBr gas or HCl in AcOH affords the desired product. 2. Alternatively, the coupling can be performed by reaction of nitro-protected L-arginine (XVIII) with isobutyl chloroformate in DMF in the presence of NMM, followed by reaction with protected piperidine derivative (XVI) to yield (XIX). Removal of the Boc group with HCl in AcOH or in dichloromethane/AcOH (2:1) and assembling to sulfonyl chloride intermediate (VII) with DIEA in DMF yields protected derivative (XX). Reductive cleavage of the nitro protecting group of (XX) with Pd/C, H2 in MeOH/AcOH/H2O (15:0.1:1), followed by elimination of the t-Bu protecting group in the conditions described above, yields the desired product.
【1】 Donovan, V.; Brundish, D.; Bull, A.; et al.; Design and synthesis of thrombin inhibitors: Analogues of MD-805 with reduced stereogenicity and improved potency. J Med Chem 1999, 42, 22, 4584. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(B) | 15926 | 2-methyl-1-propene; isobutylene | 115-11-7 | C4H8 | 详情 | 详情 |
(VII) | 43006 | 6-chloro-3,3-dimethyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl chloride | C11H13Cl2NO2S | 详情 | 详情 | |
(XIII) | 22853 | Arginine; 2-Amino-5-guanidinopentanoic acid | C6H14N4O2 | 详情 | 详情 | |
(XIV) | 43011 | N(5)-[amino(imino)methyl]-N(2)-[(3,3-dimethyl-1,2,3,4-tetrahydro-8-quinolinyl)sulfonyl]ornithine | C17H27N5O4S | 详情 | 详情 | |
(XV) | 43012 | 2-(4-piperidinyl)-1-ethanol | 622-26-4 | C7H15NO | 详情 | 详情 |
(XVI) | 43013 | 4-[2-(tert-butoxy)ethyl]piperidine; tert-butyl 2-(4-piperidinyl)ethyl ether | C11H23NO | 详情 | 详情 | |
(XVII) | 43014 | N-[4-[[amino(imino)methyl]amino]-1-([4-[2-(tert-butoxy)ethyl]-1-piperidinyl]carbonyl)butyl]-3,3-dimethyl-1,2,3,4-tetrahydro-8-quinolinesulfonamide | C28H48N6O4S | 详情 | 详情 | |
(XVIII) | 43017 | C11H21N5O6 | 详情 | 详情 | ||
(XIX) | 43015 | C22H42N6O6 | 详情 | 详情 | ||
(XX) | 43016 | C28H47N7O6S | 详情 | 详情 |