Dimethylformamide → HCID 69478080, compound

HRID 339607Notes

Reaction equation

HRID 339607 reaction equation
[CH:1]1[C:7]([NH2:8])=[N:6][C:4](=[O:5])[N:3]([C@@H:9]2[O:13][C@H:12]([CH2:14][OH:15])[C@@H:11]([OH:16])[C@H:10]2[F:17])[CH:2]=1.CCN([CH2:23][CH3:24])CC.[CH3:25][C:26]([Si:29](Cl)([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)([CH3:28])[CH3:27].[C:43](Cl)(=[O:50])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.CN([CH:55]=[O:56])C>CN(C1C=CN=CC=1)C.CO>[C:43]([O:16][C@H:11]1[C@H:10]([F:17])[C@H:9]([N:3]2[CH:2]=[CH:1][C:7]([NH:8][C:55](=[O:56])[C:24]3[CH:23]=[CH:12][CH:11]=[CH:10][CH:9]=3)=[N:6][C:4]2=[O:5])[O:13][C@@H:12]1[CH2:14][O:15][Si:29]([C:26]([CH3:28])([CH3:27])[CH3:25])([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)(=[O:50])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 7412Benzoyl chlorideHCID 8471TriethylamineHCID 94078tert-ButyldiphenylchlorosilaneHCID 1015071-(2-Deoxy-2-fluoropentofuranosyl)-4-imino-1,4-dihydropyrimidin-2-ol

Product 1

HCID 69478080HCID 69478080, compoundYield 82%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of 2-deoxy-2-fluorocytidine (0.32 g, 1.32 mmol) and DMAP (0.32 g, 2.60 mmol) in 5.0 mL of anhydrous DMF was added Et3N (0.27 mL, 1.95 mmol) and TBDPSCl (0.50 mL, 1.96 mmol) at 0° C. under N2 atmosphere. The resulting solution was stirred for 12 h at 50° C. and treated with MeOH (0.5 mL) at rt. After stirring the solution additionally, the solvent was removed under reduced pressure. The residue was dried under high vacuum for 24 h at room temperature. The crude product was dissolved in 10 mL of anhydrous pyridine at 0° C. under N2 atmosphere. To the solution was added to benzoyl chloride (0.4 mL, 3.40 mmol). After stirring the solution at rt for 12 h, the solution was treated with MeOH (1.0 mL) at rt. The solution was concentrated in vacuo and the residue was purified on silica gel column chromatography (Hexane:EtOAc=2:1 to 1:2 v/v) to give compound 2 (0.64 g, 0.92 mmol) in 82% yield. 1H NMR (CDCl3, 400 MHz) δ 9.31 (br, 1H), 8.45 (d, J=8.0, 1H), 7.96 (m, 4H), 7.66-7.37 (m, 15H), 7.18 (m, 2H), 6.26 (d, J=16.0, 1H), 5.50 (m, 1H), 5.48 (d, J=3.5, 0.5H), 5.34 (d, J=3.5, 0.5H), 4.52 (d, J=8.8, 1H), 4.28 (dd, J=12.0, 1.6, 1H), 3.87 (dd, J=12.0, 1.6, 1H), 1.10 (s, 9H); MS calcd for C39H38FN3O6Si m/z 692.3 (M+H)+, found 692.4.

Workup

  1. stirringAfter stirring the solution additionally
  2. customthe solvent was removed under reduced pressure
  3. customThe residue was dried under high vacuum for 24 h at room temperature
  4. dissolutionThe crude product was dissolved in 10 mL of anhydrous pyridine at 0° C. under N2 atmosphere
  5. stirringAfter stirring the solution at rt for 12 h
  6. concentrationThe solution was concentrated in vacuo
  7. customthe residue was purified on silica gel column chromatography (Hexane:EtOAc=2:1 to 1:2 v/v)

Sources & evidence

ORD record
ord-1f1334ea031848ab9c8458360c53208e
Source dataset
uspto-grants-2014_11
Patent number
US08895531B2

Reaction notes

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