Imidazole → HCID 86621229, compound

HRID 1867914Notes

Reaction equation

HRID 1867914 reaction equation
[N:1]([C@@:4]1([CH2:35][O:36][C:37](=[O:45])[C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([Cl:44])[CH:39]=2)[C@@H:8]([O:9][C:10](=[O:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C@@H:7]([O:18][C:19](=[O:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C@H:6]([N:27]2[CH:32]=[CH:31][C:30](=O)[NH:29][C:28]2=[O:34])[O:5]1)=[N+:2]=[N-:3].[NH:46]1[CH:50]=[CH:49][N:48]=[CH:47]1.C(N(CC)CC)C.P(Cl)(Cl)(Cl)=O>CC1OCCC1.O>[N:1]([C@@:4]1([CH2:35][O:36][C:37](=[O:45])[C:38]2[CH:43]=[CH:42][CH:41]=[C:40]([Cl:44])[CH:39]=2)[C@@H:8]([O:9][C:10](=[O:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C@@H:7]([O:18][C:19](=[O:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C@H:6]([N:27]2[CH:32]=[CH:31][C:30]([N:46]3[CH:50]=[CH:49][N:48]=[CH:47]3)=[N:29][C:28]2=[O:34])[O:5]1)=[N+:2]=[N-:3]

Participants

7

Reactant 4

HCID 795ImidazoleHCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 11707205Uridine, 4′-C-azido-, 2′,3′-dibenzoate 5′-(3-chlorobenzoate)

Product 1

HCID 86621229HCID 86621229, compoundYield 91.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 73012-MethyltetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of 30.0 g (47.5 mmol) 3-chlorobenzoic acid (2R,3S,4R,5R)-2-azido-3,4-bis-benzoyloxy-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester and 26.0 g (380 mmol) imidazole in 110 ml MeTHF was treated at room temperature with 19.2 g (189 mmol) triethylamine. The resulting mixture was treated at 10 to 20° C. within 30 minutes with 11.03 g (71.2 mmol) phosphorous oxychloride. The mixture was heated to 60° C. and stirred at this temperature for 5 hours. The mixture was then cooled to 15° C. and treated at this temperature with 125 ml water. The layers were separated and the aqueous layer was extracted with MeTHF (1×30 ml). From the organic layer MeTHF was completely removed by distillation and replaced by 250 ml acetonitrile. Water (50 ml) and methylene chloride (100 ml) were added and the layers were separated. The aqueous layer was extracted with methylene chloride (1×100 ml). The organic layer was filtered, the solvent was evaporated and the residue (34.2 g) dried in vacuo (<30 mbar) at 40° C. for 16 hours to afford 29.7 g (90.8%) of 3-chlorobenzoic acid (2R,3S,4R,5R)-2-azido-3,4-bis-benzoyloxy-5-(4-imidazol-1-yl-2-oxo-2H-pyrimidin-1-yl)-tetrahydro-furan-2-ylmethyl ester with an assay of 99.3% (area).

Workup

  1. temperatureThe mixture was then cooled to 15° C.
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with MeTHF (1×30 ml)
  4. customFrom the organic layer MeTHF was completely removed by distillation
  5. additionWater (50 ml) and methylene chloride (100 ml) were added
  6. customthe layers were separated
  7. extractionThe aqueous layer was extracted with methylene chloride (1×100 ml)
  8. filtrationThe organic layer was filtered
  9. customthe solvent was evaporated
  10. dry with materialthe residue (34.2 g) dried in vacuo (<30 mbar) at 40° C. for 16 hours

Sources & evidence

ORD record
ord-f817ff1ca9a34952a1ab2f899608c182
Source dataset
uspto-grants-2009_12
Patent number
US07632940B2

Reaction notes

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