Methanol → 4-N-acetyl-5'-O-(4,4'-dimethoxytrityl)-2'-O-(2-cyanoethoxymethyl)cytidine

HRID 1694675

Reaktionsgleichung

Reaktionsgleichung von HRID 1694675
[C:1]([CH2:3][CH2:4][O:5][CH2:6][O:7][C@@H:8]1[C@H:12]([OH:13])[C@@H:11]([CH2:14][OH:15])[O:10][C@H:9]1[N:16]1[CH:23]=[CH:22][C:20]([NH2:21])=[N:19][C:17]1=[O:18])#[N:2].N1[CH:29]=[CH:28]C=CC=1.[CH3:30][O:31][C:32]1[CH:53]=[CH:52][C:35]([C:36](Cl)([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[C:37]2[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=2)=[CH:34][CH:33]=1.C[OH:55]>>[C:28]([NH:21][C:20]1[CH:22]=[CH:23][N:16]([C@@H:9]2[O:10][C@H:11]([CH2:14][O:15][C:36]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)([C:37]3[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=3)[C:35]3[CH:52]=[CH:53][C:32]([O:31][CH3:30])=[CH:33][CH:34]=3)[C@@H:12]([OH:13])[C@H:8]2[O:7][CH2:6][O:5][CH2:4][CH2:3][C:1]#[N:2])[C:17](=[O:18])[N:19]=1)(=[O:55])[CH3:29]

Komponenten

5

Edukt 4

HCID 887MethanolHCID 1049Pyridine2×HCID 968311,1'-(Chlorophenylmethylene)bis(4-methoxybenzene)HCID 672790102'-O-(2-Cyanoethoxymethyl)cytidine

Produkt 1

HCID 866307224-N-acetyl-5'-O-(4,4'-dimethoxytrityl)-2'-O-(2-cyanoethoxymethyl)cytidineAusbeute 83 %

Versuchsvorschrift

2′-O-(2-Cyanoethoxymethyl)cytidine (9.9 g, 26.8 mmol) was subjected to azeotropic distillation with pyridine, and then was dried with a vacuum pump for 30 minutes. The residue was dissolved in 190 mL of THF, and 43 g of pyridine (538 mmol) and 20 g of molecular sieve 4 A were added under an argon atmosphere, and the mixture was stirred for 10 minutes. To the reaction solution was added 11.8 g of 4,4′-dimethoxytrityl chloride 11.8 g (34.9 mmol) by 3 portions every 1 hour, and the mixture was further stirred for 1 hour. After 2 mL of methanol was added and the reaction solution was stirred for 2 minutes, the reaction solution was filtrated with a celite, and was washed with ethylacetate. After concentrating the filtrate with evaporation, the residue was dissolved in ethyl acetate, and was separated with a saturated aqueous sodium bicarbonate solution. After the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, the solvent was distilled off. The obtained residue was purified by silica gel chromatography to obtain the objective compound (15 g, yield 83%).

Aufarbeitung

  1. customwas dried with a vacuum pump for 30 minutes
  2. dissolutionThe residue was dissolved in 190 mL of THF
  3. stirringthe mixture was further stirred for 1 hour
  4. stirringthe reaction solution was stirred for 2 minutes
  5. filtrationthe reaction solution was filtrated with a celite
  6. washwas washed with ethylacetate
  7. concentrationAfter concentrating the filtrate
  8. customwith evaporation
  9. dissolutionthe residue was dissolved in ethyl acetate
  10. customwas separated with a saturated aqueous sodium bicarbonate solution
  11. washAfter the organic layer was washed with saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. distillationthe solvent was distilled off
  14. customThe obtained residue was purified by silica gel chromatography

Quellen und Nachweise

ORD-Eintrag
ord-8a5de0a1cfe04a60b91b7635ddece64e
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08158775B2

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