Ammonia → Sonedenoson

HRID 966388Notes

Reaction equation

HRID 966388 reaction equation
Cl[C:2]1[N:10]=[C:9]([O:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@@H:21]1[O:33][C@H:32]([CH2:34][O:35]C(=O)C)[C@@H:27]([O:28]C(=O)C)[C@H:22]1[O:23]C(=O)C.[NH3:39]>C(O)C>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([CH2:13][CH2:12][O:11][C:9]2[N:10]=[C:2]([NH2:39])[C:3]3[N:4]=[CH:5][N:6]([C:7]=3[N:8]=2)[C@@H:21]2[O:33][C@H:32]([CH2:34][OH:35])[C@@H:27]([OH:28])[C@H:22]2[OH:23])=[CH:15][CH:16]=1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 591072566-Chloro-2-[2-(4-chlorophenyl)-ethoxy]-9-(2,3,5-tri-o-acetyl-beta-d-ribofuranosyl)purine

Product 1

HCID 9910098SonedenosonYield 99%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

A reactor was charged with 6-chloro-2-[2-(4-chlorophenyl)ethoxy]-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (243.8 g, 0.43 mol, Example 2, Step D) in ethanol (3,660 mL). The reactor was chilled to below −33° C., and ammonia (1500 g) is charged into the reactor. The reactor was sealed, then heated to 100° C. and the reaction was monitored by HPLC. Upon completion (approximately 5 hours), the reactor was cooled, vented, and the contents concentrated under reduced pressure. The crude product is purified by column chromatography eluting with dichloromethane/methanol. The pure fractions were concentrated under reduced pressure to about four liters of solvent and the product collected by vacuum filtration. The off-white solid was washed with dichloromethane and dried in vacuo to yield 82 grams of analytically pure (>99%) product as an off-white solid. Additional fractions were combined to provide an additional 73 g of product of lower purity (90-98%). Combined typical yield: 54%.

Workup

  1. temperatureThe reactor was chilled to below −33° C.
  2. customThe reactor was sealed
  3. temperatureUpon completion (approximately 5 hours), the reactor was cooled
  4. concentrationthe contents concentrated under reduced pressure
  5. customThe crude product is purified by column chromatography
  6. washeluting with dichloromethane/methanol
  7. concentrationThe pure fractions were concentrated under reduced pressure to about four liters of solvent
  8. filtrationthe product collected by vacuum filtration
  9. washThe off-white solid was washed with dichloromethane
  10. customdried in vacuo

Sources & evidence

ORD record
ord-4b445ea750c6403481e321f8f2da1580
Source dataset
uspto-grants-2005_10
Patent number
US06951932B2

Reaction notes

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