【结 构 式】 |
【分子编号】19181 【品名】6-amino-1-[3-(cyclopentyloxy)-4-methoxybenzyl]-5-nitroso-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone 【CA登记号】 |
【 分 子 式 】C17H20N4O4S 【 分 子 量 】376.43636 【元素组成】C 54.24% H 5.36% N 14.88% O 17% S 8.52% |
合成路线1
该中间体在本合成路线中的序号:(VIII)Isovanillin (I) is an available starting material to obtain 3-cyclopentyloxy-4-methoxybenzaldehyde (II), which is converted into the corresponding oxime (III) by treatment with hydroxylamine hydrochloride / sodium acetate trihydrate and NaHCO3. The oxime (III) is reduced to benzylamine (IV) by means hydrogen gas and catalyzed by Raney-Nickel. The reaction of benzylamine (IV) with carbon disulfide and ethyl chloroformate gives the corresponding benzyl isothiocyanate (V), which is converted into thiourea (VI) by means ammonia solution. The cyclization of thiourea (VI) with potasium tert-butoxide and ethyl cyanoacetate yields the corresponding 2-thiouracil (VII), which is converted into 5-nitroso derivative (VIII) by treatment with acetic acid and sodium nitrite solution. The hydrogenation of 5-nitroso-uracil (VIII) with hydrogen gas and neutral Raney-nickel gives diaminouracil compound (IX), which is converted into the isobutyrilaminouracil derivative (XI) by means NaHCO3 and isobutyric anhydride (X). Compound (XI) is refluxed in NaOH to afford 2-thioxantine (XII), which is converted into 2,6-dithioxantine (XIII) by means phosphorus pentasulfide in pyridine. Finally, the reaction of compound (XIII) with ethylamine gives the 2-thioisoguanine (XIV), which is desulfurized by neutral Raney-Nickel and converted into the desired purine hydrochloride by means hydrochloric acid.
【1】 Cavalla, D.; Hoefer, P.; Gehrig, A.; Wintergest, P. (Euroceltique SA); Novel chemical cpds. having PDE-IV inhibition activity. EP 0705265; JP 1997500376; US 5939422; WO 9500516 . |
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) | 18455 | 3-hydroxy-4-methoxybenzaldehyde; Isovanillin | 621-59-0 | C8H8O3 | 详情 | 详情 |
(II) | 16510 | 3-(cyclopentyloxy)-4-methoxybenzaldehyde | C13H16O3 | 详情 | 详情 | |
(III) | 19176 | 3-(cyclopentyloxy)-4-methoxybenzaldehyde oxime | C13H17NO3 | 详情 | 详情 | |
(IV) | 19177 | 3-(cyclopentyloxy)-4-methoxybenzylamine; [3-(cyclopentyloxy)-4-methoxyphenyl]methanamine | C13H19NO2 | 详情 | 详情 | |
(V) | 19178 | 3-(cyclopentyloxy)-4-methoxybenzyl isothiocyanate; 2-(cyclopentyloxy)-4-(isothiocyanatomethyl)-1-methoxybenzene | C14H17NO2S | 详情 | 详情 | |
(VI) | 19179 | N-[3-(cyclopentyloxy)-4-methoxybenzyl]thiourea | C14H20N2O2S | 详情 | 详情 | |
(VII) | 19180 | 6-amino-1-[3-(cyclopentyloxy)-4-methoxybenzyl]-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone | C17H21N3O3S | 详情 | 详情 | |
(VIII) | 19181 | 6-amino-1-[3-(cyclopentyloxy)-4-methoxybenzyl]-5-nitroso-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone | C17H20N4O4S | 详情 | 详情 | |
(IX) | 19182 | 5,6-diamino-1-[3-(cyclopentyloxy)-4-methoxybenzyl]-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone | C17H22N4O3S | 详情 | 详情 | |
(X) | 19183 | 2-methylbutyric anhydride | 1468-39-9 | C10H18O3 | 详情 | 详情 |
(XI) | 19184 | N-[6-amino-1-[3-(cyclopentyloxy)-4-methoxybenzyl]-4-oxo-2-thioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]-2-methylpropanamide | C21H28N4O4S | 详情 | 详情 | |
(XII) | 19185 | 3-[3-(cyclopentyloxy)-4-methoxybenzyl]-8-isopropyl-2-thioxo-1,2,3,7-tetrahydro-6H-purin-6-one | C21H26N4O3S | 详情 | 详情 | |
(XIII) | 19186 | 3-[3-(cyclopentyloxy)-4-methoxybenzyl]-8-isopropyl-3,7-dihydro-1H-purine-2,6-dithione | C21H26N4O2S2 | 详情 | 详情 | |
(XIV) | 19187 | 3-[3-(cyclopentyloxy)-4-methoxybenzyl]-6-(ethylamino)-8-isopropyl-3,7-dihydro-2H-purine-2-thione | C23H31N5O2S | 详情 | 详情 |