Diisopropylethylamine → 6-Azido-2-fluoro-9-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)purine

HRID 1646666Notes

Reaction equation

HRID 1646666 reaction equation
[CH2:1]([O:8][C@H:9]1[C@H:25]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C@@H:24]([CH2:34][O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[O:23][CH:10]1OC(=O)C1C=CC([N+]([O-])=O)=CC=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[N:52]([C:55]1[N:63]=[C:62]([F:64])[N:61]=[C:60]2[C:56]=1[NH:57][CH:58]=[N:59]2)=[N+:53]=[N-:54]>ClCCCl.ClCCl>[N:52]([C:55]1[N:63]=[C:62]([F:64])[N:61]=[C:60]2[C:56]=1[N:57]=[CH:58][N:59]2[C@@H:10]1[O:23][C@H:24]([CH2:34][O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C@@H:25]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C@@H:9]1[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[N+:53]=[N-:54]

Participants

6

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 970762,3,5-Tri-O-benzyl-1-O-(4-nitrobenzoyl)-D-arabinofuranoseHCID 198012676-azido-2-fluoro-7H-purine

Product 1

HCID 544897616-Azido-2-fluoro-9-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)purineYield 24.6%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 2,3,5-tri-O-benzyl-1-α-D-arabinofuranosylchloride (freshly prepared from 1.9 g of 2,3,5-tri-O-benzyl-1-O-p-nitrobenzoyl-D-arabinofuranose), N,N-diisopropylethylamine (0.58 mL) and 6-azido-2-fluoropurine (0.50 g) in 10 mL of anhydrous 1,2-dichloroethane was heated at reflux overnight. Additional N,N-diisopropylethylamine (0.26 mL) was added and heating was continued for an additional 24 hours. The mixture was cooled to ambient temperature and diluted with dichloromethane (60 mL) and washed sequentially with 10% aqueous sodium hydroxide (NaOH), water, 1N phosphoric acid (H3PO4), saturated NaCl and then dried over MgSO4 along with decolorizing carbon. The dried solution was filtered through celite and concentrated in vacuo. The residue was purified by silica gel chromatography with gradient elution from 3:1 Hexane:ethyl acetate to 100% ethyl acetate to obtain 0.40 g of the title compound as a colorless oil; IR (neat) 3031, 2922, 2867, 2126, 1608 cm-1 ; 1H NMR (DMSO-d6, 360 MHz) δ3.65-3.75 (m, 2H), 4.16 (q, J=5 Hz, 1H), 4.22 (d, J=11.8 Hz), 4.42 (t, J=5.5 Hz, 1H), 4.47 (d, J=11.8 Hz, 1H), 4.51 (s, 2H), 4.58 (t, J=5.5 Hz, 1H), 4.62 (d, J=12.0 Hz, 1H), 4.68 (d, J=12.0 Hz, 1H), 6.41 (d, J=5.5 Hz, 1H), 6.9-6.95 (m, 2H) 7.1-7.2 (m, 3H), 7.25-7.4 (m, 10H), 8.48 (s, 1H); UV (MeOH) λmax, 286 nm; MS (EI+, m/z) 582 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. temperatureheating
  4. washwashed sequentially with 10% aqueous sodium hydroxide (NaOH), water, 1N phosphoric acid (H3PO4), saturated NaCl
  5. dry with materialdried over MgSO4 along with decolorizing carbon
  6. filtrationThe dried solution was filtered through celite and
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel chromatography with gradient elution from 3:1 Hexane

Sources & evidence

ORD record
ord-c2e760113de6479bb1270021495b60a8
Source dataset
uspto-grants-1993_01
Patent number
US05180824

Reaction notes

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