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【结 构 式】

【分子编号】36962

【品名】[(2R,5S)-5-[4-amino-5-fluoro-2-oxo-1(2H)-pyrimidinyl]-1,3-oxathiolan-2-yl]methyl dihydrogen phosphate

【CA登记号】

【 分 子 式 】C8H11FN3O6PS

【 分 子 量 】327.2301252

【元素组成】C 29.36% H 3.39% F 5.81% N 12.84% O 29.34% P 9.47% S 9.8%

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:(XX)

The reaction of 1,4-dithiane-2,5-diol (XII) with 2-(benzoyloxy)acetaldehyde (XIII) in hot pyridine gives 5-acetoxy-2-(benzoyloxymethyl)-1,3-oxathiolane (XIV), which is condensed with fully silylated cytosine (XV) (obtained by silylation of cytosine (XVI) with HMDS) by means of TBDMS-OTf, yielding, after acetylation with Ac2O, a mixture of the desired racemic-cis substituted fluorocytosine (XVII) along with its racemic trans isomer, which are separated by flash chromatography. The deacylation of (XVII) with ammonia in methanol gives the racemic cis-2-(hydroxymethyl)-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane (XVIII), which is phosphorylated with POCl3 and water in trimethyl phosphate yielding the racemic phosphate (XIX). The enantioselective dephosphorylation of (XIX) with 5'-nucleotidase (Sigma), affords a mixture of the (+)-(cis)-dephosphorylated compound (XXI) and unreacted (-)-(cis)-compound (XX) that are separated by column chromatography. Finally, (XX) is dephosphorylated by means of alkaline phosphatase (Sigma) to afford the target compound.

1 Dionne, G. (BioChem Pharma Inc.); 1,3-Oxathiolane nucleoside analogues. EP 0526253; JP 1995500317; US 5538975; WO 9303027 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XII) 36958 1,4-dithiane-2,5-diol 40018-26-6 C4H8O2S2 详情 详情
(XIII) 15605 2-oxoethyl benzoate C9H8O3 详情 详情
(XIV) 36964 [5-(acetoxy)-1,3-oxathiolan-2-yl]methyl benzoate C13H14O5S 详情 详情
(XV) 36959 5-fluoro-N-(trimethylsilyl)-2-[(trimethylsilyl)oxy]-4-pyrimidinamine; N-[5-fluoro-2-[(trimethylsilyl)oxy]-4-pyrimidinyl]-N-(trimethylsilyl)amine C10H20FN3OSi2 详情 详情
(XVI) 16747 4-amino-5-fluoro-2(1H)-pyrimidinone; 5-fluorocytosine 2022-85-7 C4H4FN3O 详情 详情
(XVII) 36960 [(2R,5S)-5-[4-(acetamido)-5-fluoro-2-oxo-1(2H)-pyrimidinyl]-1,3-oxathiolan-2-yl]methyl benzoate C17H16FN3O5S 详情 详情
(XVIII) 36961 4-amino-5-fluoro-1-[(2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone C8H10FN3O3S 详情 详情
(XIX) 64685 (rac)-({(2R*,5S*)-5-[4-amino-5-fluoro-2-oxo-1(2H)-pyrimidinyl]-1,3-oxathiolan-2-yl}methyl dihydrogen phosphate) C8H11FN3O6PS 详情 详情
(XX) 36962 [(2R,5S)-5-[4-amino-5-fluoro-2-oxo-1(2H)-pyrimidinyl]-1,3-oxathiolan-2-yl]methyl dihydrogen phosphate C8H11FN3O6PS 详情 详情
(XXI) 36963 4-amino-5-fluoro-1-[(2S,5R)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone C8H10FN3O3S 详情 详情
Extended Information