Tin tetrachloride → HCID 57867413, compound

HRID 1516280Notes

Reaction equation

HRID 1516280 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]([NH2:11])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][NH:6]2.C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.C(O[C@@H:28]1[C:32]([F:34])([CH3:33])[C@@:31]([O:36][C:37](=[O:39])[CH3:38])([CH3:35])[CH:30]([CH2:40][O:41][C:42](=[O:49])[C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[O:29]1)(=O)C.Cl[Sn](Cl)(Cl)Cl.C(=O)(O)[O-].[Na+]>C(#N)C>[C:42]([O:41][CH2:40][C@@H:30]1[C:31]([O:36][C:37](=[O:39])[CH3:38])([CH3:35])[C@:32]([F:34])([CH3:33])[CH:28]([N:6]2[CH:5]=[N:4][C:3]3[C:7]2=[N:8][C:9]([NH2:11])=[N:10][C:2]=3[Cl:1])[O:29]1)(=[O:49])[C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1

Participants

7

Reactant 5

HCID 24287Tin tetrachlorideHCID 516892Sodium BicarbonateHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 86634318HCID 86634318, compoundHCID 1785084356-chloro-1H-purin-2-amine

Product 1

HCID 57867413HCID 57867413, compoundYield 310%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a stirred solution of 6-chloro-9H-purin-2-amine (about 0.18 g, 1.08 mmol) in acetonitrile (about 6 ml) was added N,O-Bis(trimethylsilyl)acetamide (about 1.59 ml, 6.5 mmol) at room temperature and refluxed for about 2 hours. To this added (2R,4R)-5-(benzoyloxymethyl)-3-fluoro-3,4-dimethyltetrahydrofuran-2,4-diyl diacetate (about 0.20 g, 0.54 mmol) in acetonitrile (about 6 ml) drop wise at about 0° C., and added SnCl4 (about 0.09 ml, 0.81 mmol) then refluxed for about 2 hours. Completion of the reaction monitored by thin-layer chromatography and neutralized the reaction mixture with saturated sodium bicarbonate solution. Aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with water, brine and dried over sodium sulphate. Concentration under reduced pressure and purification by silica gel column chromatography using 2% methanol in dichloromethane as eluent furnished title compound (0.8 g) as a colorless solid. Yield: 33%; 1H NMR (300 MHz, CDCl3): δ 8.29 (d, 1H, J=4.2 Hz), 8.06-8.03 (m, 2H), 7.59-7.56 (m, 1H), 7.49-7.44 (m, 2H), 6.80 (d, 1H, J=21.6 Hz), 5.09 (s, 2H), 4.83-4.78 (m, 2H), 4.51-4.44 (m, 1H), 2.17 (s, 3H), 1.89 (d, 3H, J=2.4 Hz), 1.48 (d, 3H, J=23.1 Hz); ES Mass: [M+1] 478 (30%), [M+Na] 500 (30%); HPLC:. 93.1%.

Workup

  1. temperaturerefluxed for about 2 hours
  2. temperaturethen refluxed for about 2 hours
  3. extractionAqueous layer was extracted with ethyl acetate
  4. washthe combined organic layers were washed with water, brine
  5. dry with materialdried over sodium sulphate
  6. concentrationConcentration
  7. customunder reduced pressure and purification by silica gel column chromatography

Sources & evidence

ORD record
ord-71a5ecb3e2ed406b9ed99a093634ecfb
Source dataset
uspto-grants-2012_07
Patent number
US08227431B2

Reaction notes

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