4-Toluenesulfonyl chloride → 4-Chloro-7-[3,5-bis-o-(2,4-dichlorophenylmethyl)-2-c-fluoromethyl-beta-d-ribofuranosyl]-7h-pyrrolo[2,3-d]pyrimidine

HRID 2252689Notes

Reaction equation

HRID 2252689 reaction equation
[Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C@@H:11]3[O:26][C@H:25]([CH2:27][O:28][CH2:29][C:30]4[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:31]=4[Cl:37])[C@@H:14]([O:15][CH2:16][C:17]4[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=4[Cl:24])[C@@:12]3([CH2:38]O)[OH:13])[C:4]=2[N:5]=[CH:6][N:7]=1.C(N(CC)CC)C.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.[F-:58].C([N+](CCCC)(CCCC)CCCC)CCC>ClCCl.CN(C)C1C=CN=CC=1>[Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C@@H:11]3[O:26][C@H:25]([CH2:27][O:28][CH2:29][C:30]4[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:31]=4[Cl:37])[C@@H:14]([O:15][CH2:16][C:17]4[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=4[Cl:24])[C@@:12]3([CH2:38][F:58])[OH:13])[C:4]=2[N:5]=[CH:6][N:7]=1

Participants

7

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 2724141Tetrabutylammonium FluorideHCID 872853644-Chloro-7-[3,5-bis-o-(2,4-dichlorophenylmethyl)-2-c-hydroxymethyl-beta-d-ribofuranosyl]-7h-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 872853684-Chloro-7-[3,5-bis-o-(2,4-dichlorophenylmethyl)-2-c-fluoromethyl-beta-d-ribofuranosyl]-7h-pyrrolo[2,3-d]pyrimidineYield 31.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of the compound from Example 24, Step A (63 mg, 0.1 mmol) in anhydrous dichloromethane (5 mL) under argon, were added 4-dimethylaminopyridine (DMAP) (2 mg, 0.015 mmol) and triethylamine (62 μL, 0.45 mmol). The solution was cooled in an ice bath and p-toluenesulfonyl chloride (30 mg, 0.15 mmol) was added. The reaction was stirred at room temperature overnight, washed with NaHCO3 (2×10 mL), water (10 mL), brine (10 mL), dried over Na2SO4 and concentrated to a pink solid in vacuo. The solid was dissolved in anhydrous THF (5 mL) and cooled in an icebath. Tetrabutylammonium fluoride (1M solution in THF, 1 mL, 1 mmol) was added and the mixture stirred at room temperature for 4 h. The solvent was removed in vacuo, the residue taken up in dichloromethane, and washed with NaHCO3 (2×10 mL), water (10 mL) and brine (10 mL). The dichloromethane layer was dried over anhydrous Na2SO4, concentrated in vacuo, and purified by flash chromatography (SiO2, 2:1 hexanes/EtOAc) to afford the title compound (20 mg) as a white solid.

Workup

  1. temperatureThe solution was cooled in an ice bath
  2. washwashed with NaHCO3 (2×10 mL), water (10 mL), brine (10 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to a pink solid in vacuo
  5. dissolutionThe solid was dissolved in anhydrous THF (5 mL)
  6. temperaturecooled in an icebath
  7. stirringthe mixture stirred at room temperature for 4 h
  8. customThe solvent was removed in vacuo
  9. washwashed with NaHCO3 (2×10 mL), water (10 mL) and brine (10 mL)
  10. dry with materialThe dichloromethane layer was dried over anhydrous Na2SO4
  11. concentrationconcentrated in vacuo
  12. custompurified by flash chromatography (SiO2, 2:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-bd584b5c02254850bb21d74722336934
Source dataset
uspto-grants-2008_01
Patent number
US07323453B2

Reaction notes

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