Pyridine → HCID 178430605, compound

HRID 2393313Notes

Reaction equation

HRID 2393313 reaction equation
[C:1]([NH:20][CH2:21][C@H:22]1[O:26][C@@H:25]([N:27]2[CH:35]=[C:33]([CH3:34])[C:31](=[O:32])[NH:30][C:28]2=[O:29])[CH2:24][C@@H:23]1[OH:36])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:37]1C=C[CH:40]=[CH:39][CH:38]=1.C(N(C(C)C)CC)(C)C.[CH:52]([N:55]([CH:63]([CH3:65])[CH3:64])[P:56](Cl)[O:57]CCC#N)([CH3:54])[CH3:53]>C(Cl)Cl.C(OCC)(=O)C>[C:38]([CH2:39][CH2:40][PH:56]([O:36][C@@H:23]1[C@@H:22]([CH2:21][NH:20][C:1]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[O:26][C@@H:25]([N:27]2[CH:35]=[C:33]([CH3:34])[C:31](=[O:32])[NH:30][C:28]2=[O:29])[CH2:24]1)([N:55]([CH:52]([CH3:53])[CH3:54])[CH:63]([CH3:64])[CH3:65])[OH:57])#[N:37]

Participants

7

Reactant 4

HCID 1049PyridineHCID 81531DiisopropylethylamineHCID 27348442-Cyanoethyl N,N-diisopropylchlorophosphoramiditeHCID 54327478HCID 54327478, compound

Product 1

HCID 178430605HCID 178430605, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

0.15 g (0.31 mmol) of 5'-tritylamino-5'-deoxy-thymidine [prepared as described in step (a) above] was dried by azeotropic distillation with pyridine and then dissolved in 2 ml of methylene chloride. 0.23 ml (1.2 mmol) of N,N-diisopropyl-N-ethylamine was then added to the resulting solution, after which 0.08 ml (0.36 mmol) of 2-cyanoethyl N,N-diisopropylchlorophosphoramidite was added over a period of 2 minutes in a stream of nitrogen. The resulting mixture was then stirred at room temperature for 60 minutes. At the end of this time, it was confirmed that the starting compound had disappeared by thin layer chromatography, and the reaction mixture was diluted with 30 ml of ethyl acetate. The resulting organic solution was washed with a saturated aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order. The organic layer was through a 1PS (trade mark) filter paper (Whatman), and the filtrate was freed from the solvent by distillation under reduced pressure. The resulting residue was purified by column chromatography through 15 g of silica gel (70-230 mesh), using ethyl acetate as the eluent, to give 0.19 g (yield 89%) of the title compound as a foamy substance.

Workup

  1. washThe resulting organic solution was washed with a saturated aqueous solution of sodium hydrogencarbonate and with a saturated aqueous solution of sodium chloride, in that order
  2. filtrationfilter paper (Whatman)
  3. distillationthe filtrate was freed from the solvent by distillation under reduced pressure
  4. customThe resulting residue was purified by column chromatography through 15 g of silica gel (70-230 mesh)

Sources & evidence

ORD record
ord-7b0a35c21d9e43f285b8b54a52921274
Source dataset
uspto-grants-1998_09
Patent number
US05807837

Reaction notes

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