Imidazole → HCID 86621230, compound

HRID 1867915Notes

Reaction equation

HRID 1867915 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C(N(CC)CC)C.P(Cl)(Cl)(Cl)=O.[N:18]([C:21]1([CH2:38][O:39][C:40](=[O:48])[C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([Cl:47])[CH:42]=2)[CH:28]2[CH:24]([O:25][CH:26]([CH3:29])[O:27]2)[CH:23]([N:30]2[CH:35]=[CH:34][C:33](=O)[NH:32][C:31]2=[O:37])[O:22]1)=[N+:19]=[N-:20]>C(Cl)Cl.O>[N:18]([C:21]1([CH2:38][O:39][C:40](=[O:48])[C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([Cl:47])[CH:42]=2)[CH:28]2[CH:24]([O:25][CH:26]([CH3:29])[O:27]2)[CH:23]([N:30]2[CH:35]=[CH:34][C:33]([N:1]3[CH:5]=[CH:4][N:3]=[CH:2]3)=[N:32][C:31]2=[O:37])[O:22]1)=[N+:19]=[N-:20]

Participants

7

Reactant 4

HCID 795ImidazoleHCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 86621231HCID 86621231, compound

Product 1

HCID 86621230HCID 86621230, compoundYield 99.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 0.69 g (10.11 mmol) imidazole and 1.07 g (10.5 mmol) triethylamine in 9 ml methylene chloride was added dropwise at −5 to 0° C. within 15 minutes 0.49 g (3.22 mmol) phosphorous oxychloride. After 15 minutes at −5° C., the resulting suspension was treated with 1.00 g (2.15 mmol) 3-chloro-benzoic acid 4-azido-6-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-2-methyl-tetrahydro-furo[3,4-d]-1,3-dioxol-4-ylmethyl ester followed by 1 ml methylene chloride. The suspension was allowed to warm to room temperature within 15 minutes and then stirred at room temperature for 69 hours. The suspension was cooled to 0° C. and treated at this temperature with 10 ml water. The suspension was allowed to warm to room temperature and the layers were separated. The aqueous layer was extracted with methylene chloride (2×5 ml). The combined organic layer was dried over MgSO4, filtered, concentrated in vacuo, and dried in vacuo (<10 mbar) at 25° C. for 22 hours to afford 1.07 g (96%) of 3-chlorobenzoic acid 4-azido-6-(4-imidazol-1-yl-2-oxo-2H-pyrimidin-1-yl)-2-methyl-tetrahydro-furo[3,4-d]-1,3-dioxol-4-ylmethyl ester as a beige foam.

Workup

  1. temperatureThe suspension was cooled to 0° C.
  2. temperatureto warm to room temperature
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with methylene chloride (2×5 ml)
  5. dry with materialThe combined organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customdried in vacuo (<10 mbar) at 25° C. for 22 hours

Sources & evidence

ORD record
ord-7dcd3cf449ed4e7bb8b15142b94fc888
Source dataset
uspto-grants-2009_12
Patent number
US07632940B2

Reaction notes

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