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【结 构 式】

【分子编号】37427

【品名】5-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1H-imidazole-4-carboxamide

【CA登记号】

【 分 子 式 】C9H14N4O5

【 分 子 量 】258.23412

【元素组成】C 41.86% H 5.46% N 21.7% O 30.98%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(I)

This compound can be obtained in two different ways: 1) The acylation of 5-amino-1-beta-D-ribofuranosylimidazole-4-carboxamide (I) with propionic anhydride (A) in pyridine gives the corresponding tri-O-propionyl derivative (II), which by treatment with POCl3 and triethylamine in CHCl3 is converted into 5-amino-4-cyano-1-(2,3,5-tri-O-propionyl-beta-D-ribofuranosyl)imidazole (III). The hydrolysis of (III) with methanolic ammonia yields 5-amino-4-cyano-1-beta-D-ribofuranosylimidazole (IV), which is finally cyclized with phenylcyanamide (V) in methanolic ammonia at 180 C in a pressure vessel. This cyclization can also be performed with (III) and (V) directly, using the same procedure. 2) By reaction of 2-bromoadenosine (VI) with aniline (VII) in 2-methoxyethanol at 120 C.

1 Marumoto, R.; et al.; Synthesis and coronary vasodilating activity of 2-substituted adenosines. Chem Pharm Bull 1975, 23, 4, 759-774.
2 Marumoto, R.; et al. (Takeda Chemical Industries, Ltd.); 2,6-Diaminonebularine derivs.. US 3936439 .
3 Marumoto, R.; et al. (Takeda Chemical Industries, Ltd.); Production of 2,6-diaminonebularines. DE 2845435 .
4 Castaner, J.; Serradell, M.N.; Blancafort, P.; Thorpe, P.J.; CV-1808. Drugs Fut 1981, 6, 4, 222.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(A) 20095 propionic anhydride 123-62-6 C6H10O3 详情 详情
(I) 37427 5-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1H-imidazole-4-carboxamide C9H14N4O5 详情 详情
(II) 37428 [(2R,3R,4R,5R)-5-[5-amino-4-(aminocarbonyl)-1H-imidazol-1-yl]-3,4-bis(propionyloxy)tetrahydro-2-furanyl]methyl propionate C18H26N4O8 详情 详情
(III) 37429 [(2R,3R,4R,5R)-5-(5-amino-4-cyano-1H-imidazol-1-yl)-3,4-bis(propionyloxy)tetrahydro-2-furanyl]methyl propionate C18H24N4O7 详情 详情
(IV) 37430 5-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1H-imidazole-4-carbonitrile C9H12N4O4 详情 详情
(V) 37431 phenylcyanamide C7H6N2 详情 详情
(VI) 37432 (2R,3R,4S,5R)-2-(6-amino-2-bromo-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol C10H12BrN5O4 详情 详情
(VII) 12294 Aniline; Phenylamine 62-53-3 C6H7N 详情 详情

合成路线2

该中间体在本合成路线中的序号:(I)

The cyclization of the imidazolyl riboside (I) with [13C]-formic acid ethyl ester (II) by means of sodium ethoxide in refluxing ethanol gives labeled inosine (III), which is acetylated with Ac2O and pyridine yielding the triacetate (IV). The nitration of (IV) with ammonium nitrate and trifluoroacetic anhydride affords the 1-nitroinosine (V), which is rearranged with 15NH4Cl in acetonitrile/water to provide the doubly labeled inosine (VI). The reaction of (VI) with SOCl2 gives the chloropurine (VII), which is condensed with the dideuterated 2-aminocyclopentanol (rac-trans)-(VIII) (obtained by hydrogenation of the unsaturated analogue (rac-trans)-(IX)) by means of NaHCO3 in isopropanol providing a diastereomeric mixture (X). The deacetylation of (X) with tert-butylamine in methanol furnishes a mixture of the target compound along with its diastereomer, which is separated by preparative HPLC.

1 Wadsworth, A.H.; et al.; Synthesis of isotopically labelled versions of adenosine agonist GR79236. J Label Compd Radiopharm 2000, 43, 1, 11.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(IV),(VI) 38014 (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate C16H18N4O8 详情 详情
(I) 37427 5-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1H-imidazole-4-carboxamide C9H14N4O5 详情 详情
(II) 16602 ethyl formate 109-94-4 C3H6O2 详情 详情
(II) 45175 ethyl formate C3H6O2 详情 详情
(III) 38013 9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one C10H12N4O5 详情 详情
(III) 45176 9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one C10H12N4O5 详情 详情
(IV) 45177 (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate C16H18N4O8 详情 详情
(V) 38015 (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(1-nitro-6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate C16H17N5O10 详情 详情
(V) 45178 (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(1-nitro-6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate C16H17N5O10 详情 详情
(VI) 45179 (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate C16H18N4O8 详情 详情
(VII) 38016 (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-chloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate C16H17ClN4O7 详情 详情
(VII) 45180 (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-chloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate C16H17ClN4O7 详情 详情
(VIII) 38010 (1S,2S)-2-aminocyclopentanol C5H11NO 详情 详情
(VIII) 45181 (1S,2S)-2-aminocyclopentanol C5H11NO 详情 详情
(IX) 38017 (1S,2S)-2-amino-3-cyclopenten-1-ol C5H9NO 详情 详情
(X) 38018 (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-[[(1S,2S)-2-hydroxycyclopentyl]amino]-9H-purin-9-yl)tetrahydro-3-furanyl acetate C21H27N5O8 详情 详情
(X) 45182 (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-[[(1S,2S)-2-hydroxycyclopentyl]amino]-9H-purin-9-yl)tetrahydro-3-furanyl acetate C21H27N5O8 详情 详情
Extended Information