Thymine → HCID 15332428, compound

HRID 659841Notes

Reaction equation

HRID 659841 reaction equation
C(O[CH:5]1[O:21][C@H:20]([CH2:22][O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@:11]([CH:31]=[CH2:32])([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C@H:6]1[O:7][C:8](=[O:10])[CH3:9])(=O)C.[NH:33]1[CH:41]=[C:39]([CH3:40])[C:37](=[O:38])[NH:36][C:34]1=[O:35].C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O>C(#N)C>[C:8]([O:7][C@@H:6]1[C@:11]([CH:31]=[CH2:32])([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C@@H:20]([CH2:22][O:23][CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[O:21][C@H:5]1[N:33]1[CH:41]=[C:39]([CH3:40])[C:37](=[O:38])[NH:36][C:34]1=[O:35])(=[O:10])[CH3:9]

Participants

6

Reactant 4

HCID 1135ThymineHCID 65367Trimethylsilyl triflateHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 15332424HCID 15332424, compound

Product 1

HCID 15332428HCID 15332428, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of compound 22 (4.24 g, 9.6 mmol) and thymine (2.43 g, 19.3 mmol) in anhydrous acetonitrile (100 cm3) was added N,O-bis(trimethylsilyl)acetamide (11.9 cm3, 48.1 mmol). The reaction mixture was stirred at reflux for 30 min. After cooling to 0° C., trimethylsilyl triflate (3.2 cm3, 16.4 mmol) was added dropwise and the solution was stirred for 24 h at room temperature. The reaction was quenched with cold saturated aqueous sodium hydrogencarbonate (100 cm3) and the resulting mixture was extracted with dichloromethane (3×50 cm3). The combined extract was washed with saturated aqueous sodium hydrogencarbonate (2×50 cm3) and brine (2×50 cm3) and dried (Na2SO4). The extract was evaporated under reduced pressure and the residue was purified by silica gel column chromatography using dichloromethane/methanol (99:1, v/v) as eluent to give nucleoside 23 as a white foam (4.03 g, 83%). δH (CDCl3) 8.78 (1H, br s, NH), 7.75 (1H, s, 6-H), 7.38-7.26 (10H, m, Bn), 6.49 (1H, d, J 8.1, 1′-H), 5.99-5.88 (2H, m, 2′-H and 1″-H), 5.54-5.48 (2H, m, 2″-Ha, 2″-Hb), 4.91-4.50 (4H, m, Bn), 4.34 (1H, s, 4′-H), 3.80 (1H, m, 5′-Ha), 3.54 (1H, m, 5′-Hb), 2.11 (3H, s, COCH3), 1.48 (3H, s, CH3). δC (CDCl3) 170.1 (C═O), 163.8 (C-4), 151.0 (C-2), 138.9, 136.9 (Bn), 136.1 (C-6), 132.0 (C-1″), 128.7, 128.5, 128.2, 127.8, 127.7, 127.5, 127.5, 127.1 (Bn), 120.7 (C-2″), 111.3 (C-5), 85.4 (C-1′), 85.2 (C-3′), 84.3 (C-4′), 76.0 (C-2′), 73.7 (C-5′), 69.3, 67.6 (Bn), 20.6 (COCH3), 11.7 (CH3). Found: C, 66.3; H, 6.0; N, 5.1; C28H30N2O7 requires C, 66.4; H, 6.0; N, 5.5%.

Workup

  1. temperatureat reflux for 30 min
  2. stirringthe solution was stirred for 24 h at room temperature
  3. customThe reaction was quenched with cold saturated aqueous sodium hydrogencarbonate (100 cm3)
  4. extractionthe resulting mixture was extracted with dichloromethane (3×50 cm3)
  5. extractionThe combined extract
  6. washwas washed with saturated aqueous sodium hydrogencarbonate (2×50 cm3) and brine (2×50 cm3)
  7. dry with materialdried (Na2SO4)
  8. customThe extract was evaporated under reduced pressure
  9. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-85d0ac2c7fb94179824af6abe1145ec1
Source dataset
uspto-grants-2011_12
Patent number
US08080644B2

Reaction notes

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