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【结 构 式】

【分子编号】55528

【品名】(1R,4S)-4-[(methoxycarbonyl)oxy]-2-cyclopenten-1-yl acetate

【CA登记号】

【 分 子 式 】C9H12O5

【 分 子 量 】200.19128

【元素组成】C 54% H 6.04% O 39.96%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(II)

The reaction of the commercially available (1S-cis)-2-cyclopentan-1,4-diol 4-acetate (I) with methyl pyrocarbonate and DMAP in THF gives the carbonate ester (II), which by reaction with nitromethane (III), triisopropyl phosphite and a Pd catalyst, yields (1R-cis)-1-acetoxy-4-(nitromethyl)-2-cyclopentene (IV). The hydrolysis of (IV) by means of Ts-OH in methanol affords the corresponding alcohol (V), which by treatment with O3, NaOMe and NaBH4 in methanol provides (1R-cis)-4-(hydroxymethyl)-2-cyclopenten-1-ol (VI). The selective monotritylation of the primary OH group of (VI) with trityl chloride (VII) in pyridine gives the trityl ether (VIII), which is condensed with 2-amino-6-chloropurine (IX) by means of Pd(PPh3)4 in THF to yield the adduct (X). The destritylation of (X) with HOAc/water affords the hydroxymethyl compound (XI), which is finally dechlorinated by hydrolysis with hot HCl or NaOH to provide the target (-)-carbovir. Alternatively, the dechlorination of (XI) can be performed by reaction of (XI) with liquid ammonia at 75-80 C in a Parr bomb to give the diaminopurine (XII), which is finally submitted to an enzymatic deamination with adenosine deaminase (from calf intestinal mucosa).

1 Vince, R.; Peterson, M.L.; Lackey, J.W.; Mook, R.A. Jr.; Partridge, J.J. (GlaxoSmithKline plc); Synthesis of purine substd. cyclopentene derivs.. US 5126452 .
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) 45407 (1R,4S)-4-hydroxy-2-cyclopenten-1-yl acetate; (1S,4R)-4-acetoxy-2-cyclopentenol 60410-16-4 C7H10O3 详情 详情
(II) 55528 (1R,4S)-4-[(methoxycarbonyl)oxy]-2-cyclopenten-1-yl acetate C9H12O5 详情 详情
(III) 39563 nitromethane 75-52-5 CH3NO2 详情 详情
(IV) 55529 (1R,4S)-4-(nitromethyl)-2-cyclopenten-1-yl acetate C8H11NO4 详情 详情
(V) 55530 (1R,4S)-4-(nitromethyl)-2-cyclopenten-1-ol C6H9NO3 详情 详情
(VI) 45405 (1R,4S)-4-(hydroxymethyl)-2-cyclopenten-1-ol C6H10O2 详情 详情
(VII) 28630 Triphenylchloromethane; 1-[Chloro(diphenyl)methyl]benzene; Trityl chloride 76-83-5 C19H15Cl 详情 详情
(VIII) 55531 (1R,4S)-4-[(trityloxy)methyl]-2-cyclopenten-1-ol C25H24O2 详情 详情
(IX) 11644 6-Chloro-9H-purin-2-amine; 6-Chloro-9H-purin-2-ylamine; 2-Amino-6-chloropurine 10310-21-1 C5H4ClN5 详情 详情
(X) 55532 6-chloro-9-{(1R,4S)-4-[(trityloxy)methyl]-2-cyclopenten-1-yl}-9H-purin-2-amine; 6-chloro-9-{(1R,4S)-4-[(trityloxy)methyl]-2-cyclopenten-1-yl}-9H-purin-2-ylamine C30H26ClN5O 详情 详情
(XI) 17650 [(1S,4R)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl]methanol C11H12ClN5O 详情 详情
(XII) 55533 [(1S,4R)-4-(2,6-diamino-9H-purin-9-yl)-2-cyclopenten-1-yl]methanol C11H14N6O 详情 详情
Extended Information