Trimethylsilyl triflate → 1-(2-c-Methyl-2,3,5-tri-o-benzoyl-beta-d-ribofuranosyl)imidazo[4,5-d]pyridazin-4-one

HRID 402315Notes

Reaction equation

HRID 402315 reaction equation
[NH:1]1[C:5]2=[CH:6][N:7]=[N:8][CH:9]=[C:4]2[N:3]=[CH:2]1.C(O[C@@H:19]1[O:41][C@H:40]([CH2:42][O:43][C:44](=[O:51])[C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[C@@H:30]([O:31][C:32](=[O:39])[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C@@:20]1([CH3:52])[O:21][C:22](=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)(=O)C1C=CC=CC=1.C1CCN2C(=NCCC2)CC1.[Si]([O:68]S(C(F)(F)F)(=O)=O)(C)(C)C.[Na]>C(#N)C>[CH3:52][C@@:20]1([O:21][C:22](=[O:29])[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C@H:30]([O:31][C:32](=[O:39])[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C@@H:40]([CH2:42][O:43][C:44](=[O:51])[C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[O:41][C@H:19]1[N:1]1[C:5]2=[CH:6][N:7]=[N:8][C:9](=[O:68])[C:4]2=[N:3][CH2:2]1

Participants

7

Reactant 5

HCID 65367Trimethylsilyl triflateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 5360545SodiumHCID 53708751H-Imidazo[4,5-d]pyridazineHCID 108755601,2,3,5-Tetra-O-benzoyl-2-C-methyl-beta-D-ribofuranose

Product 1

HCID 1317314311-(2-c-Methyl-2,3,5-tri-o-benzoyl-beta-d-ribofuranosyl)imidazo[4,5-d]pyridazin-4-oneYield 16.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of imidazo[4,5-d]pyridazine (3.48 g, 25.5 mmol) [for preparation see Journal of Heterocyclic Chemistry, 1969, Vol 6, 93] in dry acetonitrile (35 mL) was added 1,2,3,5-tetra-O-benzoyl-2-C-methyl-β-D-ribofuranose (14.48 g, 25.0 mmol) at 20° C. and stirred for 15 mn. DBU (11.5 mL, 76.3 mmol) was added at 0° C. and the solution was stirred for 15 nm at 0° C. TMSOTf (24.7 mL, 127.8 mmol) was added at 0° C. and the mixture was heated at 80° C. for 20 hours. The reaction mixture was poured into an aqueous solution of sodium hydrogenocarbonate and extracted by ethyl acetate. The organic layer was evaporated to dryness to give a yellow powder. The crude product was purified on silica gel using dichloromethane/methanol (99.3/0.7) as eluant to give a slight yellow powder which was crystallized from isopropanol to give the title compound (2.45 g) as a white powder.

Workup

  1. stirringthe solution was stirred for 15 nm at 0° C
  2. extractionextracted by ethyl acetate
  3. customThe organic layer was evaporated to dryness
  4. customto give a yellow powder
  5. customThe crude product was purified on silica gel
  6. customto give a slight yellow powder which
  7. customwas crystallized from isopropanol

Sources & evidence

ORD record
ord-bad0ee830fc444b897dbd7a22837a1bb
Source dataset
uspto-grants-2014_06
Patent number
US08742101B2

Reaction notes

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