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

HRID 30150

Reaction equation

[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]

Participants

Conditions

Temperature: 0 °C

Procedure

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.

Workup

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

Sources & evidence

ORD record: ord-48cd7fee41774e7cb1c0a4219d97505d
Source dataset: uspto-grants-2008_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07423025B2

Linked notes

Loading…