6-Methyluracil → 1-(2',3',5'-Tri-O-benzoyl-beta-L-ribofuranosyl)-6-methyluracil

HRID 478770

反応式

HRID 478770 の反応式
[CH3:1][C:2]1[NH:7][C:6](=[O:8])[NH:5][C:4](=[O:9])[CH:3]=1.CC1(C)[SiH2][SiH]=NC(C)(C)C1(C)C.S([O-])([O-])(=O)=O.[NH4+].[NH4+].C[Si](C)(C)OC1N=C(O[Si](C)(C)C)C=C(C)N=1.C(O[CH:50]1[O:72][C@@H:71]([CH2:73][O:74][C:75](=[O:82])[C:76]2[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=2)[C@H:61]([O:62][C:63](=[O:70])[C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=2)[C@@H:51]1[O:52][C:53](=[O:60])[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)(=O)C.C[Si](OS(C(F)(F)F)(=O)=O)(C)C>C(#N)C.C1(C)C=CC=CC=1>[C:53]([O:52][C@H:51]1[C@@H:61]([O:62][C:63](=[O:70])[C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=2)[C@H:71]([CH2:73][O:74][C:75](=[O:82])[C:76]2[CH:77]=[CH:78][CH:79]=[CH:80][CH:81]=2)[O:72][C@@H:50]1[N:7]1[C:2]([CH3:1])=[CH:3][C:4](=[O:9])[NH:5][C:6]1=[O:8])(=[O:60])[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1

参加物

9

反応物 6

HCID 122836-MethyluracilHCID 65367Trimethylsilyl triflateHCID 3564182,4-Bis(trimethylsilyloxy)-6-methylpyrimidineHCID 6097028Ammonium SulfateHCID 126715131-o-Acetyl-2,3,5-tri-o-benzoyl-l-riboseHCID 1317189914,4,5,5,6,6-hexamethyl-3H-azadisiline

生成物 1

HCID 120432031-(2',3',5'-Tri-O-benzoyl-beta-L-ribofuranosyl)-6-methyluracil

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
135 °C

実験手順

A mixture of 6-methyluracil (2.52 g, 20.0 mmol), hexamethyldisilazine (50 mL) and ammonium sulfate (100 mg ) were refluxed at 135° C. for 6 h. The solvent was removed in vacuo and the residue that obtained was co-evaporated twice with dry toluene (2×50 mL) to remove last traces of hexamethyldisilazine. The solid thus obtained was dried under vacuum for 6 h. A solution of the 2,4-bis(trimethylsilyloxy)-6-methylpyrimidine (20.0 mmol) in dry acetonitrile (100 mL) was added 1-O-acetyl-2,3,5-tri-O-benzoyl-L-ribofuranose (10.12 g, 20 mmol) and trimethylsilyltriflate (5.78 g, 26.0 mmol. The reaction mixture was stirred under argon at room temperature for 16 h. The reaction mixture was concentrated in vacuo and the residue was dissolved in dichloromethane (200 mL). The organic layer was washed with sat. sodium bicarbonate (200 mL) and brine (100 mL), dried over sodium sulfate and concentrated to yield a white foam. Further separation of the crude product by silica gel flash column chromatography using the CH2Cl2→EtOAc as the eluent gave two products. Yield of the 2nd fraction 4.50 g (42%). 1H NMR (CDCl3) δ2.28 (s, 3H, CH3), 4.65-4.81 (m, 3H, C4′H and C5′H), 5.60 (m, 1H, C3′H), 5.72 (s, 1H), 6.11 (m, 1H), 7.24-8.06 (m, 16H, PhH) and 9.40 (br s, 1H, NH). The first fraction (4.20 g) did not correspond to the desired compound according to 1H NMR.

後処理

  1. customThe solvent was removed in vacuo
  2. customthe residue that obtained
  3. customto remove last traces of hexamethyldisilazine
  4. customThe solid thus obtained
  5. customwas dried under vacuum for 6 h
  6. concentrationThe reaction mixture was concentrated in vacuo
  7. dissolutionthe residue was dissolved in dichloromethane (200 mL)
  8. washThe organic layer was washed with sat. sodium bicarbonate (200 mL) and brine (100 mL)
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated
  11. customto yield a white foam
  12. customFurther separation of the crude product by silica gel flash column chromatography
  13. customgave two products

出典と根拠

ORDレコード
ord-f418f87c35ba4156a8513f7443d4f3f8
出典データセット
uspto-grants-2003_11
特許番号
US06642206B2

関連ノート

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