Water → HCID 11487746, compound

HRID 434268Notes

Reaction equation

HRID 434268 reaction equation
[CH2:1]([O:8][C@:9]1([CH2:33]O)[C@@H:13]([CH2:14][O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:12][C@@H:11]([N:23]2[CH:31]=[C:29]([CH3:30])[C:27](=[O:28])[NH:26][C:24]2=[O:25])[C@H:10]1[OH:32])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CS(Cl)(=O)=O.O.[H-].[Na+]>N1C=CC=CC=1.CN(C=O)C>[CH2:1]([O:8][C@@:9]12[CH2:33][O:32][C@@H:10]1[C@H:11]([N:23]1[CH:31]=[C:29]([CH3:30])[C:27](=[O:28])[NH:26][C:24]1=[O:25])[O:12][C@@H:13]2[CH2:14][O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 54132005HCID 54132005, compound

Product 1

HCID 11487746HCID 11487746, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolvent2×HCID 6228DimethylformamideSolvent

Procedure

A solution of compound 27 (2.26 g, 4.83 mmol) in anhydrous pyridine (20 cm3) was stirred at −40° C. and a solution of methanesulphonyl chloride (0.482 cm3, 4.83 mmol) in anhydrous pyridine (10 cm3) was added. The reaction mixture was stirred at room temperature for 17 h, water (50 cm3) was added, and the mixture was extracted with dichloromethane (2×100 cm3). The combined organic phase was washed with saturated aqueous sodium hydrogencarbonate (3×100 cm3), dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by silica gel column chromatography using dichloromethane/methanol (99:1, v/v) as eluent to give an intermediate which after evaporation of the solvents was dissolved in anhydrous DMF (15 cm3). This solution was added dropwise to a suspension of 60% sodium hydride (461 mg, 11.5 mmol) in anhydrous DMF (15 cm3) at 0° C. The reaction was stirred at room temperature for 30 min, then quenched with water (60 cm3). After neutralisation using dilute aqueous hydrochloric acid, the mixture was dissolved in dichloromethane (150 cm3), washed with saturated aqueous sodium hydrogencarbonate (3×100 cm3) and dried (Na2SO4). The solvents were evaporated and the residue was purified by silica gel column chromatography using dichloromethane/methanol (99:1, v/v) as eluent to give nucleoside 28 as a white foam (2.00 g, 93%). δH (CDCl3) 9.13 (1H, br s, NH), 7.55 (1H, d, J 1.4, 6-H), 7.40-7.26 (Bn), 5.99 (1H, d, J 2.5, 1′-H), 5.30 (1H, d, J 2.7, 2′-H), 4.88-4.57 (6H, m, 1″-Ha, 1″-Hb, Bn), 4.22-4.19 (1H, m, 4′-H), 3.92 (1H, dd, J 6.2, 10.8, 5′-Ha), 3.82 (1H, dd, J 3.7, 10.8, 5′-Hb), 1.91 (3H, d, J 1.3, CH3). δC (CDCl3) 163.8 (C-4), 150.3 (C-2), 137.6 (C-6), 137.5, 137.0 (Bn), 128.7, 128.6, 128.2, 128.0, 127.8, 127.3 (Bn), 109.8 (C-5), 85.7 (C-3′), 84.1 (C-1′), 83.5 (C-4′), 79.7 (C-1″), 73.9 (C-2′), 73.6 (C-5′), 68.6, 67.8 (Bn), 12.4 (CH3). FAB m/z 451 [M+H]+, 473 [M+Na]+. Found: C, 66.3; H, 5.9; N, 6.1; C25H26N2O6 requires C, 66.7; H, 5.8; N, 6.2%.

Workup

  1. extractionthe mixture was extracted with dichloromethane (2×100 cm3)
  2. washThe combined organic phase was washed with saturated aqueous sodium hydrogencarbonate (3×100 cm3)
  3. dry with materialdried (Na2SO4)
  4. customevaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography
  6. customv/v) as eluent to give an intermediate which
  7. customafter evaporation of the solvents
  8. dissolutionwas dissolved in anhydrous DMF (15 cm3)
  9. stirringThe reaction was stirred at room temperature for 30 min
  10. customquenched with water (60 cm3)
  11. dissolutionthe mixture was dissolved in dichloromethane (150 cm3)
  12. washwashed with saturated aqueous sodium hydrogencarbonate (3×100 cm3)
  13. dry with materialdried (Na2SO4)
  14. customThe solvents were evaporated
  15. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a0b2fe1565f747d3a0a99096c1fa942f
Source dataset
uspto-grants-2003_12
Patent number
US06670461B1

Reaction notes

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