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【结 构 式】

【分子编号】29887

【品名】Sodium cyclopentadienide

【CA登记号】4984-82-1

【 分 子 式 】C5H5Na

【 分 子 量 】88.084468

【元素组成】C 68.18% H 5.72% Na 26.1%

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 regioselective reaction of cyclopentadiene (I) and sodium or commercial sodium cyclopentadienide (II) with benzyl chloromethyl ether (III) by means of the chiral catalyst (-)-diisopinocampheylborane in THF, followed by hydroxylation with H2O2/NaOH, gives (1S-trans)-2-(benzyloxymethyl)-3-cyclopenten-1-ol (IV), which is regioselectively epoxidized with tert-butyl hydroperoxide and vanadyl acetylacetonate in 2,2,4-trimethylpentane, yielding [1S-(1alpha,2alpha,3beta,5alpha)-2-(benzyloxymethyl)-6-oxabicyclo[3.1.0]hexan-3-ol (V). The protection of (V) with benzyl bromide and NaH affords the corresponding ether (VI), which is condensed with 6-O-benzylguanine (VII) by means of LiH in DMF to give the guanine derivative (VIII). The protection of the amino group of (VIII) with 4-methoxyphenyl(diphenyl)chloromethane (IX), TEA and DMAP in dichloromethane gives intermediate (X), which is oxidized at the free hydroxyl group with methylphosphonic acid, DCC and oxalic acid in DMSO or Dess Martin periodinane in dichloromethane, yielding the cyclopentanone derivative (XI). The reaction of (XI) with (i) Zn/TiCl4/CH2Br2 complex in THF/CH2Cl2, (ii) activated Zn/PbCl2/CH2I2/TiCl4 in THF/CH2Cl2 (2), (iii) Nysted reagent/TiCl4 in THF/CH2Cl2 or (iv) Tebbe reagent in toluene affords the corresponding methylene derivative (XII), which is partially deprotected with 3N HCl in hot THF, providing the dibenzylated compound (XI). Finally, this compound is treated with BCl3 in dichloromethane. (Scheme 18263401a)

1 Bisacchi, G.S.; Chao, S.T.; Bachard, C.; et al.; BMS-200475. A novel carbocyclic 2'-deoxyguanosine analog with potent and selective anti-hepatitis B virus activity in vitro. Bioorg Med Chem Lett 1997, 7, 2, 127.
2 Castaner, J.; Graul, A.; BMS-200475. Drugs Fut 1999, 24, 111, 1173.
3 Zahler, R.; Slusarchyk, W.A. (Bristol-Myers Squibb Co.); Hydroxymethyl(methylenecyclopentyl)purines and pyrimidines. EP 0481754; JP 1992282373; US 5206244 .
4 Bisacchi, G.S.; Sundeen, J.E. (Bristol-Myers Squibb Co.); Improved process for preparing the antiviral agent [1S-(1alpha, 3alpha, 4beta)]-2-amino-1,9-dihydro-9-[4-hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl]-6H-purin-6-one. WO 9809964 .
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) 11183 1,3-Cyclopentadiene C5H6 详情 详情
(II) 29887 Sodium cyclopentadienide 4984-82-1 C5H5Na 详情 详情
(III) 14560 Benzyl chloromethyl ether; 1-[(chloromethoxy)methyl]benzene 3587-60-8 C8H9ClO 详情 详情
(IV) 29888 (1S,2R)-2-[(benzyloxy)methyl]-3-cyclopenten-1-ol C13H16O2 详情 详情
(V) 29889 (1S,2R,3S,5R)-2-[(benzyloxy)methyl]-6-oxabicyclo[3.1.0]hexan-3-ol C13H16O3 详情 详情
(VI) 29890 (1S,2R,3S,5R)-3-(benzyloxy)-2-[(benzyloxy)methyl]-6-oxabicyclo[3.1.0]hexane; benzyl (1S,2R,3S,5R)-2-[(benzyloxy)methyl]-6-oxabicyclo[3.1.0]hex-3-yl ether C20H22O3 详情 详情
(VII) 14383 6-(benzyloxy)-9H-purin-2-ylamine; 6-(benzyloxy)-9H-purin-2-amine 19916-73-5 C12H11N5O 详情 详情
(VIII) 29891 (1S,2S,3S,5S)-5-[2-amino-6-(benzyloxy)-9H-purin-9-yl]-3-(benzyloxy)-2-[(benzyloxy)methyl]cyclopentanol C32H33N5O4 详情 详情
(IX) 12700 4-[Chloro(diphenyl)methyl]phenyl methyl ether; 1-[Chloro(diphenyl)methyl]-4-methoxybenzene; p-Anisylchlorodiphenylmethane 14470-28-1 C20H17ClO 详情 详情
(X) 29892 (1S,2S,3S,5S)-3-(benzyloxy)-5-(6-(benzyloxy)-2-[[(4-methoxyphenyl)(diphenyl)methyl]amino]-9H-purin-9-yl)-2-[(benzyloxy)methyl]cyclopentanol C52H49N5O5 详情 详情
(XI) 29893 (2R,3S,5S)-3-(benzyloxy)-5-(6-(benzyloxy)-2-[[(4-methoxyphenyl)(diphenyl)methyl]amino]-9H-purin-9-yl)-2-[(benzyloxy)methyl]cyclopentanone C52H47N5O5 详情 详情
(XII) 29894 6-(benzyloxy)-9-[(1S,3R,4S)-4-(benzyloxy)-3-[(benzyloxy)methyl]-2-methylenecyclopentyl]-N-[(4-methoxyphenyl)(diphenyl)methyl]-9H-purin-2-amine; N-(6-(benzyloxy)-9-[(1S,3R,4S)-4-(benzyloxy)-3-[(benzyloxy)methyl]-2-methylenecyclopentyl]-9H-purin-2-yl)-N-[(4-methoxyphenyl)(diphenyl)methyl]amine 142217-80-9 C53H49N5O4 详情 详情
(XIII) 29895 2-amino-9-[(1S,3R,4S)-4-(benzyloxy)-3-[(benzyloxy)methyl]-2-methylenecyclopentyl]-1,9-dihydro-6H-purin-6-one 142217-81-0 C26H27N5O3 详情 详情
Extended Information