Acetic Acid → HCID 46843958, compound

HRID 1920695Notes

Reaction equation

HRID 1920695 reaction equation
C([O:9][C@H:10]1[C@:14]([F:16])([CH3:15])[C@H:13]([N:17]2[CH:25]=[N:24][C:23]3[C:18]2=[N:19][C:20]([NH2:27])=[N:21][C:22]=3Cl)[O:12][C@@H:11]1[CH2:28][O:29]C(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.Cl.[NH:39]1[CH2:42][CH2:41][CH2:40]1.C(N(CC)CC)C.C[O-].[Na+].C(O)(=O)C>C(O)C>[NH2:27][C:20]1[N:19]=[C:18]2[C:23]([N:24]=[CH:25][N:17]2[C@@H:13]2[O:12][C@H:11]([CH2:28][OH:29])[C@@H:10]([OH:9])[C@:14]2([F:16])[CH3:15])=[C:22]([N:39]2[CH2:42][CH2:41][CH2:40]2)[N:21]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 10942334Sodium MethoxideHCID 12308726Azetidine hydrochlorideHCID 533058126-Chloro-9-(3,5-di-O-benzoyl-2-deoxy-2-fluoro-2-methyl-beta-D-ribofuranosyl)-9H-purin-2-amine

Product 1

HCID 46843958HCID 46843958, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

To a 350 mL of dry seal pressure flask (Chemglass) were added (2R,3R,4R,5R)-5-(2-amino-6-chloro-9H-purin-9-yl)-2-(benzoyloxymethyl)-4-fluoro-4-methyltetrahydrofuran-3-yl benzoate (12, 3.6 g, 6.85 mmol) and 150 mL of absolute ethanol. Azetidine hydrochloride (2.56 g, 27.4 mmol) was added and then followed by triethylamine (4.16 g, 41.1 mmol). The supension was stirred and heated to 70° C. while sealed for 5 hours. All the starting material was consumed but the benzoyl groups remained as shown by TLC. Sodium methoxide (7.8 mL, 34.3 mmol, 25% solution in methanol) was added to the mixture and heated at 50° C. The reaction was complete after 3.5 h. The reaction mixture was allowed to cool to room temperature and neutralized by addition of glacial acetic acid (0.41 g, 6.85 mmol). The mixture was concentrated under reduced pressure and then the residue was triturated with ethyl acetate. The resulting solid was removed by filtration and the solid was washed with EtOAc (2×15 mL). The filtrate was concentrated under reduced pressure and the residue was purified via column chromatography (Analogix, 120 g cartridge, gradient of 0 to 15% MeOH in DCM). The pure product containing fractions were combined, concentrated under reduced pressure and dried (50° C., 0.2 mmHg, 17 h) to a light pink colored foam solid (2.15 g, 6.35 mmol, 93%).

Workup

  1. customTo a 350 mL of dry
  2. customseal pressure flask (Chemglass)
  3. customwhile sealed for 5 hours
  4. customAll the starting material was consumed
  5. temperatureheated at 50° C
  6. temperatureto cool to room temperature
  7. concentrationThe mixture was concentrated under reduced pressure
  8. customthe residue was triturated with ethyl acetate
  9. customThe resulting solid was removed by filtration
  10. washthe solid was washed with EtOAc (2×15 mL)
  11. concentrationThe filtrate was concentrated under reduced pressure
  12. customthe residue was purified via column chromatography (Analogix, 120 g cartridge, gradient of 0 to 15% MeOH in DCM)
  13. additionThe pure product containing fractions
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0afb2bd031974be993207aba19c27537
Source dataset
uspto-grants-2012_05
Patent number
US08173621B2

Reaction notes

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