【结 构 式】 |
【分子编号】65471 【品名】 【CA登记号】 |
【 分 子 式 】C20H27NO7 【 分 子 量 】393.43692 【元素组成】C 61.06% H 6.92% N 3.56% O 28.47% |
合成路线1
该中间体在本合成路线中的序号:(XXXV)The preparation of the cyclopentylamino intermediates (I) and (XIX) is shown in Scheme 4. Reaction of (1S,4R)-4-acetoxy-2-cyclopentenol (XXX) with di-tert-butyl iminodicarboxylate in the presence of NaH and Pd(PPh3)4 produces the di-Boc-protected aminocyclopentenol (XXXI), which undergoes dihydroxylation to triol (XXXII) by means of N-methylmorpholine N-oxide and a catalytic amount of osmium tetroxide. After acidic deprotection of the di-Boc derivative (XXXII), the resulting amino triol (XXXIII) is converted to the key acetonide (I) upon heating with 2,2-dimethoxypropane and catalytic HCl in acetone (1, 2). The O-hydroxyethyl derivative (XIX) is prepared by protection of aminoalcohol (I) as the benzyl carbamate (XXXIV), followed by O-alkylation with ethyl bromoacetate and potassium tert-butoxide to give (XXXV). Subsequent reduction of ester (XXXV) with LiBH4 in THF furnishes the corresponding hydroxyethyl derivative (XXXVI), from which the N-(benzyloxycarbonyl) group is removed by catalytic hydrogenation over Pd/C (3). Scheme 4.
【1】 Guile, S., Hardern, D., Willis, P., Springthorpe, B., Ingall, A. (AstraZeneca AB; AstraZeneca plc). Novel triazolo(4,5-d)pyrimidine compounds. EP 1135391, JP 2002531567, JP 2007084551, US 2003144305, US 2006025590, US 6525060, WO 0034283. |
【2】 Bohlin, M., Lassen, B., Cosgrove, S. (AstraZeneca AB). New crystalline and amorphous form of triazolo(4,5-d)pyrimidine compound. CA 2408596, EP 1289992, EP 1493745, JP 2003535092, US 2003181469, US 2007173518, WO 0192262. |
【3】 Larsson, U., Magnusson, M., Musil, T., Palmgren, A. (AstraZeneca AB). Triazolo pyrimidine compounds. CA 2408914, EP 1299390, JP 2003535093, US 2003148888, US 2006041132, US 2007049755, US 7067663, WO 0192263. |
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) | 65443 | (3aR,4S,6R,6aS)-6-Aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-ol; (3aS,4R,6S,6aR)-6-Hydroxy-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-amine | 155899-66-4 | C8H15NO3 | 详情 | 详情 |
(XIX) | 65458 | 2-[[(3aR,4S,6R,6aS)-6-Aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl]oxy]ethanol | 274693-55-9 | C10H19NO4 | 详情 | 详情 |
(XXX) | 45407 | (1R,4S)-4-hydroxy-2-cyclopenten-1-yl acetate; (1S,4R)-4-acetoxy-2-cyclopentenol | 60410-16-4 | C7H10O3 | 详情 | 详情 |
(XXXI) | 65467 | (1S,4R)-4-[(N,N-di-Boc)amino]-2-cyclopentenol | C15H25NO5 | 详情 | 详情 | |
(XXXII) | 65468 | C15H27NO7 | 详情 | 详情 | ||
(XXXIII) | 65469 | C5H11NO3.HCl | 详情 | 详情 | ||
(XXXIV) | 65470 | N-[(3aS,4R,6S,6aR)-Tetrahydro-6-hydroxy-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl]carbamicacid phenylmethyl ester | 274693-53-7 | C16H21NO5 | 详情 | 详情 |
(XXXV) | 65471 | C20H27NO7 | 详情 | 详情 | ||
(XXXVI) | 65472 | N-[(3aS,4R,6S,6aR)-Tetrahydro-6-(2-hydroxyethoxy)-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl]carbamic acid phenylmethyl ester | 274693-54-8 | C18H25NO6 | 详情 | 详情 |