Pyridine → HCID 178430606, compound

HRID 1488557Notes

Reaction equation

HRID 1488557 reaction equation
[CH:1]1[C:14]2[C:5](=[CH:6][C:7]3[C:12]([C:13]=2[CH2:15][S:16][CH2:17][C@H:18]2[O:22][C@@H:21]([N:23]4[CH:31]=[C:29]([CH3:30])[C:27](=[O:28])[NH:26][C:24]4=[O:25])[CH2:20][C@@H:19]2[OH:32])=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH:4]=[CH:3][CH:2]=1.[N:33]1C=C[CH:36]=[CH:35][CH:34]=1.C(N(C(C)C)CC)(C)C.[CH:48]([N:51]([CH:59]([CH3:61])[CH3:60])[P:52](Cl)[O:53]CCC#N)([CH3:50])[CH3:49]>O1CCCC1>[C:34]([CH2:35][CH2:36][PH:52]([O:32][C@@H:19]1[C@@H:18]([CH2:17][S:16][CH2:15][C:13]2[C:12]3[C:7]([CH:6]=[C:5]4[C:14]=2[CH:1]=[CH:2][CH:3]=[CH:4]4)=[CH:8][CH:9]=[CH:10][CH:11]=3)[O:22][C@@H:21]([N:23]2[CH:31]=[C:29]([CH3:30])[C:27](=[O:28])[NH:26][C:24]2=[O:25])[CH2:20]1)([N:51]([CH:48]([CH3:49])[CH3:50])[CH:59]([CH3:60])[CH3:61])[OH:53])#[N:33]

Participants

6

Reactant 4

HCID 1049PyridineHCID 81531DiisopropylethylamineHCID 27348442-Cyanoethyl N,N-diisopropylchlorophosphoramiditeHCID 86751372HCID 86751372, compound

Product 1

HCID 178430606HCID 178430606, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

74 mg (0.165 mmol) of 5'-[(anthracen-9-yl)methylthio]-5'-deoxythymidine [prepared as described in (a) above] were dried by azeotropic distillation with pyridine and then dissolved in 1 ml of tetrahydrofuran. 0.115 ml (0.659 mmol) of N,N-diisopropyl-N-ethylamine was added to the solution. 49 μl (0.22 mmol) of 2-cyanoethyl N,N-diisopropylchlorophosphoramidite were then added dropwise to the mixture, under an atmosphere of argon. The resulting mixture was stirred at room temperature for 1.75 hours under the same atmosphere. The tetrahydrofuran was then removed by distillation under reduced pressure. The resulting residue was dissolved in 10 ml of ethyl acetate, and the solution was washed with a 10% w/v aqueous solution of sodium carbonate and with a saturated aqueous solution of sodium chloride, in that order. The solution was dried over anhydrous sodium sulfate, and then the solvent was removed by distillation under reduced pressure, and the residue was purified by column chromatography through 10 g of silica gel (70-230 mesh), using ethyl acetate as the eluent, to give 85 mg (yield 79%) of the title compound as a foam-like substance.

Workup

  1. customThe tetrahydrofuran was then removed by distillation under reduced pressure
  2. dissolutionThe resulting residue was dissolved in 10 ml of ethyl acetate
  3. washthe solution was washed with a 10% w/v aqueous solution of sodium carbonate and with a saturated aqueous solution of sodium chloride, in that order
  4. dry with materialThe solution was dried over anhydrous sodium sulfate
  5. customthe solvent was removed by distillation under reduced pressure
  6. customthe residue was purified by column chromatography through 10 g of silica gel (70-230 mesh)

Sources & evidence

ORD record
ord-0a3e51fcd02b48acbf742eccfc818dee
Source dataset
uspto-grants-1997_10
Patent number
US05674856

Reaction notes

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