Ammonium fluoride → N4-Benzoyl-3'-O-(azidomethyl)-2'-deoxycytidine

HRID 634080Notes

Reaction equation

HRID 634080 reaction equation
[C:1]([NH:9][C:10]1[CH:33]=[CH:32][N:13]([C@@H:14]2[O:31][C@H:21]([CH2:22][O:23][Si](C(C)(C)C)(C)C)[C@@H:16]([O:17][CH2:18]SC)[CH2:15]2)[C:12](=[O:34])[N:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(NC1C=CN([C@@H]2O[C@H](CO[Si](C(C)(C)C)(C)C)[C@@H](O)C2)C(=O)N=1)(=O)C1C=CC=CC=1.[N-:66]=[N+:67]=[N-:68].[Na+].[NH4+].[F-]>C(Cl)Cl>[C:1]([NH:9][C:10]1[CH:33]=[CH:32][N:13]([C@@H:14]2[O:31][C@H:21]([CH2:22][OH:23])[C@@H:16]([O:17][CH2:18][N:66]=[N+:67]=[N-:68])[CH2:15]2)[C:12](=[O:34])[N:11]=1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 25516Ammonium fluorideHCID 33557Sodium AzideHCID 14018201N4-Benzoyl-5'-O-tert-butyldimethylsilyl-2'-deoxycytidineHCID 86649154N4-Benzoyl-3'-O-(methylthiomethyl)-5'-O-(tert-butyldimethylsilyl)-2'-deoxycytidine

Product 1

HCID 86649153N4-Benzoyl-3'-O-(azidomethyl)-2'-deoxycytidineYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 0.5580 g N4-benzoyl-3′-O-(methylthlomethyl)-5′-O-(tert-butyldimethylsilyl)-2′-deoxycytidine (6c) (1.04 mmol) dissolved in 8 mL dry CH2Cl2 were added 0.56 mL cyclohaxene and 220 μL SO2C2 (2.7 mmol) at 0° C. and stirred at the ice-cold temperature for 1 h. During this time, the starting material converted to the chlorinated product as shown by the 3′-OH (5c) compound in the TLC. The volatiles were then removed under vacuum and resuspended in dry DMF (5 mL) and treated with NaN3 (400 mg, 6.6 mmol) and stirred for 2 h at room temperature. The sample was then partitioned between water and CH2Cl2 and the organic extracts were combined and dried over Na2SO, and concentrated under vacuum. The crude sample was then dissolved in MeOH (5 mL) and treated with NH4F (600 mg, 16.2 mmol) for 20 h at room temperature. Then solvent was removed under vacuum and extracted with CH2Cl2 and the organic extract was then dried over Na2SO4 and concentrated under vacuum. The sample was then purified by silica gel column chromatography (Hex:EtOAc 1:4 to 1:10), and the product (9c) was obtained as white powdery substance (˜200 mg, 50% yield in three steps, Rf=0.5, EtOAc:Hex/5:0.5). HR-MS: Obs. m/z 387.1408, calcd for C17H19O5N6 387.1417 [M+H]+. 1H-NMR (CDC3): δH 8.30 (d, J=7.2 Hz, 1H), 7.93 (d, J=7.50 Hz, 1H), 7.66-7.51 (m, 5H), 6.18 (t, J=6.4 Hz, 1H), 4.81-4.68 (m, 2H), 4.52 (m, 1H), 4.25 (m, 1H), 4.08-3.88 (m, 2H), 2.69 (m, 1H), and 2.50 (m, 2H) ppm.

Workup

  1. additionwere added 0.56 mL cyclohaxene and 220 μL SO2C2 (2.7 mmol) at 0° C.
  2. customThe volatiles were then removed under vacuum
  3. customThe sample was then partitioned between water and CH2Cl2
  4. dry with materialdried over Na2SO
  5. concentrationconcentrated under vacuum
  6. dissolutionThe crude sample was then dissolved in MeOH (5 mL)
  7. customThen solvent was removed under vacuum
  8. extractionextracted with CH2Cl2
  9. extractionthe organic extract
  10. dry with materialwas then dried over Na2SO4
  11. concentrationconcentrated under vacuum
  12. customThe sample was then purified by silica gel column chromatography (Hex:EtOAc 1:4 to 1:10)

Sources & evidence

ORD record
ord-8d4bc9e52bb444f6b0b457cf128b9869
Source dataset
uspto-grants-2016_04
Patent number
US09322050B2

Reaction notes

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