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

HRID 30150

반응식

HRID 30150 반응식
[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]

참가 물질

9

반응물 5

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

생성물 1

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

시약·촉매·용매 3

HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매HCID 13838Hexamethyldisilazane용매

반응 조건

온도
0 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-48cd7fee41774e7cb1c0a4219d97505d
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07423025B2

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