Pyridine → 7-(2-Thienyl)-3-[2-deoxy-5-O-(4,4'-dimethoxytrityl)-beta-D-ribofuranosyl]-3H-imidazo[4,5-b]pyridine 2-cyanoethyl-N,N-diisopropylphosphoramidite

HRID 1662289Notes

Reaction equation

HRID 1662289 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[CH:11]=[CH:10][N:9]=[C:8]2[N:12]([C@@H:15]3[O:20][C@H:19]([CH2:21][O:22][C:23]([C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)([C:32]4[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=4)[C:24]4[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=4)[C@@H:17]([OH:18])[CH2:16]3)[CH:13]=[N:14][C:7]=12.N1C=CC=CC=1.[CH:52]([N:55]([CH:69]([CH3:71])[CH3:70])[P:56](N(C(C)C)C(C)C)[O:57]CCC#N)([CH3:54])[CH3:53].N1C=NN=N1>C(#N)C.O.CO>[C:15]([CH2:16][CH2:17][O:18][P:56]([N:55]([CH:69]([CH3:71])[CH3:70])[CH:52]([CH3:54])[CH3:53])[OH:57])#[N:12].[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[CH:11]=[CH:10][N:9]=[C:8]2[N:12]([C@@H:15]3[O:20][C@H:19]([CH2:21][O:22][C:23]([C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=4)([C:24]4[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=4)[C:32]4[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=4)[C@@H:17]([OH:18])[CH2:16]3)[CH:13]=[N:14][C:7]=12

Participants

8

Reactant 4

HCID 1049PyridineHCID 1281532-Cyanoethyl tetraisopropylphosphorodiamiditeHCID 674276947-(2-Thienyl)-3-[2-deoxy-5-O-(4,4'-dimethoxytrityl)-beta-D-ribofuranosyl]-3H-imidazo[4,5-b]pyridineHCID 178418441HCID 178418441, compound

Product 1

HCID 866390137-(2-Thienyl)-3-[2-deoxy-5-O-(4,4'-dimethoxytrityl)-beta-D-ribofuranosyl]-3H-imidazo[4,5-b]pyridine 2-cyanoethyl-N,N-diisopropylphosphoramiditeYield 169.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolvent3×

Procedure

Compound 7 (425 mg, 0.69 mmol) was azeotroped three times with anhydrous pyridine and then three times with anhydrous acetonitrile. This was dissolved in anhydrous acetonitrile (4.6 ml), followed by addition of 2-cyanoethyl tetraisopropylphosphorodiamidite (262 μl, 0.82 mmol)) and a 0.45 M acetonitrile solution of tetrazole (1.68 ml). This mixture was stirred for 1 hour at room temperature. After addition of anhydrous methanol (90 μl), the mixture was poured into water (50 ml) and extracted with 1% triethylamine (v/v)-containing methylene chloride (50 ml×3). After drying over Na2SO4, the solvent was distilled off under reduced pressure. The residue was purified by flash silica gel chromatography using 2% triethylamine (v/v)-containing hexane:ethyl acetate (4:1 to 3:2) as an elution solvent to give 490 mg of Compound 8 in a yield of 87%.

Workup

  1. extractionextracted with 1% triethylamine (v/v
  2. addition)-containing methylene chloride (50 ml×3)
  3. dry with materialAfter drying over Na2SO4
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThe residue was purified by flash silica gel chromatography
  6. addition)-containing hexane:ethyl acetate (4:1 to 3:2) as an elution solvent

Sources & evidence

ORD record
ord-bcde36c19c9544fd8aa9ae2f513d7303
Source dataset
uspto-grants-2011_10
Patent number
US08030478B2

Reaction notes

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