Pyridine → HCID 178430607, compound

HRID 1488558Notes

Reaction equation

HRID 1488558 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][S:12][CH2:13][C@H:14]1[O:18][C@@H:17]([N:19]2[CH:27]=[C:25]([CH3:26])[C:23](=[O:24])[NH:22][C:20]2=[O:21])[CH2:16][C@@H:15]1[OH:28].[N:29]1C=C[CH:32]=[CH:31][CH:30]=1.C(NC(C)C)(C)C.[CH:42]([N:45]([CH:53]([CH3:55])[CH3:54])[P:46](Cl)[O:47]CCC#N)([CH3:44])[CH3:43]>O1CCCC1>[C:30]([CH2:31][CH2:32][PH:46]([O:28][C@@H:15]1[C@@H:14]([CH2:13][S:12][CH2:11][C:2]2[CH:3]=[CH:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:1]=2)[O:18][C@@H:17]([N:19]2[CH:27]=[C:25]([CH3:26])[C:23](=[O:24])[NH:22][C:20]2=[O:21])[CH2:16]1)([N:45]([CH:42]([CH3:43])[CH3:44])[CH:53]([CH3:54])[CH3:55])[OH:47])#[N:29]

Participants

6

Reactant 4

HCID 1049PyridineHCID 7912DiisopropylamineHCID 27348442-Cyanoethyl N,N-diisopropylchlorophosphoramiditeHCID 67680270HCID 67680270, compound

Product 1

HCID 178430607HCID 178430607, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

79.7 mg (0.2 mmol) of 5'-[(2-naphthyl)methylthio]-5'-deoxythymidine [prepared as described in step (a) above] were dried by azeotropic distillation with pyridine and then dissolved in 2.5 ml of tetrahydrofuran. 0.084 ml (0.48 mmol) of diisopropylamine was then added to the solution. 54 μl (0.24 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 then dried over anhydrous magnesium sulfate, after which the solvent was distilled off 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 67 mg (yield 56%) 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 then dried over anhydrous magnesium sulfate
  5. distillationafter which the solvent was distilled off 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-d15ef826fc124f6eb8736dfd9be215f1
Source dataset
uspto-grants-1997_10
Patent number
US05674856

Reaction notes

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