Trimethylsilyl triflate → 9-(2-O-Acetyl-5-O-tert-butyldiphenylsilyl-3-deoxy-3-fluorenylmethylcarbonylamino-beta-L-ribofuranosyl)-6-chloropurine

HRID 30150

反応式

HRID 30150 の反応式
[Cl:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[NH:4][CH:5]=[N:6]2.S([O-])([O-])(=O)=O.[NH4+].[NH4+].[Si:18]([O:35][CH2:36][C@@H:37]1[O:42][C@:40](C(=O)C)(O)[C@@:39](C(=O)C)([OH:46])[C@H:38]1[NH:50][C:51]([CH2:53][C:54]1[C:66]2[CH2:65][C:64]3[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=3)[C:58]=2[CH:57]=[CH:56][CH:55]=1)=[O:52])([C:31]([CH3:34])([CH3:33])[CH3:32])([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.O([Si](C)(C)C)S([C:71](F)(F)F)(=O)=O.[C:79](=[O:82])(O)[O-].[Na+]>C[Si](C)(C)N[Si](C)(C)C.C(#N)C.ClCCl>[C:79]([O:46][C@H:39]1[C@@H:38]([NH:50][C:51]([CH2:53][C:54]2[C:66]3[CH2:65][C:64]4[C:59](=[CH:60][CH:61]=[CH:62][CH:63]=4)[C:58]=3[CH:57]=[CH:56][CH:55]=2)=[O:52])[C@H:37]([CH2:36][O:35][Si:18]([C:31]([CH3:34])([CH3:32])[CH3:33])([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:42][C@@H:40]1[N:6]1[CH:5]=[N:4][C:3]2[C:7]1=[N:8][CH:9]=[N:10][C:2]=2[Cl:1])(=[O:82])[CH3:71]

参加物

9

反応物 5

HCID 65367Trimethylsilyl triflateHCID 516892Sodium BicarbonateHCID 53592776-ChloropurineHCID 6097028Ammonium SulfateHCID 1317270175-O-tert-Butyldiphenylsilyl-3-deoxy-1,2-diacetyl-3-fluorenylmethylcarbonylamino-beta-L-ribofuranose

生成物 1

HCID 1317270169-(2-O-Acetyl-5-O-tert-butyldiphenylsilyl-3-deoxy-3-fluorenylmethylcarbonylamino-beta-L-ribofuranosyl)-6-chloropurine収率 82%

試薬・触媒・溶媒 3

HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒HCID 13838Hexamethyldisilazane溶媒

反応条件

温度
0 °C

実験手順

A mixture of 6-chloropurine (0.67 g, 4.33 mmol) and ammonium sulfate (30 mg, 0.23 mmol) in 1,1,1,3,3,3-hexamethyldisilazane (30 mL) was refluxed for 3 h, then the solvent was removed in vacuo at 35-40° C. A solution of 6 (1.88 g, 2.71 mmol) in anhydrous acetonitrile (30 mL) was added to the residual solid. The resulting solution was cooled to 0° C. and trimethylsilyl triflate (0.78 mL, 4.31 mmol) was added, and the reaction was stirred at rt overnight. The resulting solution was diluted to 100 mL with dichloromethane and slowly added to an ice-cold saturated solution of sodium bicarbonate (200 mL). The organic layer was separated and the aqueous phase was extracted with dichloromethane (2×100 mL). The combined organic extracts were washed with water (50 mL), brine (50 mL), dried over magnesium sulfate, filtered and concentrated to a crude that was purified by tlc-grade silica gel flash chromatography (1:49 methanol/dichloromethane) to give 7 as a white solid (1.75 g, 82%). Rf0.14 (1:49 methanol/dichloromethane); mp 91-93° C. (dec.); [α]D25 −17.83 (c 0.42, CHCl3); UV (MeOH) λmax 264.0, 299.0; 1H NMR (CDCl3, 400 MHz) δ8.70 (s, 1H), 8.34 (s, 1H), 7.81-7.78 (m, 2H), 7.68-7.57 (m, 6H), 7.44-7.36 (m, 4H), 7.35-7.29 (m, 4H), 7.26-7.22 (m, 2H), 6.15 (s, 1H), 5.67-5.64 (m, 1H), 5.12-5.06 (m, 1H), 4.99-4.95 (m, 1H), 4.55-4.45 (m, 2H), 4.25-4.21 (m, 1H), 4.16-4.12 (m, 1H), 4.03-3.99 (m, 1H), 3.88-3.83 (m, 1H), 2.15 (s, 3H), 1.03 (s, 9H); 13C NMR (CDCl3, 100 MHz) δ 169.4, 152.0, 151.1, 150.8, 143.8, 143.5, 143.4, 141.2, 135.5, 135.3, 132.5, 132.2, 132.0, 129.7, 127.6, 127.5, 126.9, 124.7, 124.6, 119.9, 88.0, 83.2, 75.4, 66.8, 62.8, 50.9, 47.0, 26.6, 20.5, 19.0; Mass ([M+H]+) 788, ([M+Na]+) 810, ([2M+Na]+) 1597. Anal. Calcd for C43H42ClN5O6Si: C, 65.51; H, 5.37; N, 8.88. Found: C, 65.24; H, 5.54; N, 8.56.

後処理

  1. temperaturewas refluxed for 3 h
  2. customthe solvent was removed in vacuo at 35-40° C
  3. customThe organic layer was separated
  4. extractionthe aqueous phase was extracted with dichloromethane (2×100 mL)
  5. washThe combined organic extracts were washed with water (50 mL), brine (50 mL)
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated to a crude that
  9. customwas purified by tlc-grade silica gel flash chromatography (1:49 methanol/dichloromethane)

出典と根拠

ORDレコード
ord-48cd7fee41774e7cb1c0a4219d97505d
出典データセット
uspto-grants-2008_09
特許番号
US07423025B2

関連ノート

読み込み中…