Water → (R)-5-Chloro-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

HRID 2090557Notes

Reaction equation

HRID 2090557 reaction equation
[Cl:1][C:2]1[C:11]2[C:10](=[O:12])[NH:9][CH:8]=[N:7][C:6]=2[N:5]([CH3:13])[C:4](=[O:14])[C:3]=1[F:15].[CH3:16][C:17]1([CH3:36])[O:21][C@H:20]([CH2:22]OS(C2C=CC([N+]([O-])=O)=CC=2)(=O)=O)[CH2:19][O:18]1.CN1CCCC1=O.N12CCCN=C1CCCCC2.C(OC(C)C)(=O)C.O>>[Cl:1][C:2]1[C:11]2[C:10](=[O:12])[N:9]([CH2:22][C@@H:20]3[CH2:19][O:18][C:17]([CH3:36])([CH3:16])[O:21]3)[CH:8]=[N:7][C:6]=2[N:5]([CH3:13])[C:4](=[O:14])[C:3]=1[F:15]

Participants

7

Reactant 6

HCID 962WaterHCID 7915Isopropyl Acetate2×HCID 13387N-methyl-2-pyrrolidoneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 71475086(S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl-4-nitrobenzenesulfonateHCID 1358730885-Chloro-6-fluoro-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

Product 1

HCID 67378564(R)-5-Chloro-3-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-6-fluoro-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

Conditions

Temperature
60 °C

Procedure

Combine 5-chloro-6-fluoro-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (5.00 g, 21.8 mmol), (S)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl-4-nitrobenzenesulfonate (7.60 g, 24.0 mmol), and N-methylpyrrolidinone (25.0 mL, 259 mmol). Add 1,8-Diazabicyclo[5.4.0]undec-7-ene (3.58 mL, 24.0 mmol) to the suspension. Heat to 60° C. and stir overnight. Add isopropyl acetate (50.0 mL, 427 mmol) followed by water (50.0 mL, 2780 mmol) while maintaining the temperature above 50° C. Stir at 60° C. for 1 hour, separate the phases and transfer the aqueous phase to a flask. Add isopropyl acetate (50.0 mL, 427 mmol) to the flask and stir at 60° C. for 1 hour and then separate the layers. Combine the organic phases and concentrate under vacuum to about 25 mL to give a solid. Cool to ambient temperature and stir for no longer than 2 hours, collect the solid by filtration, dry under vacuum overnight to give the title compound.

Workup

  1. temperaturewhile maintaining the temperature above 50° C
  2. stirringStir at 60° C. for 1 hour
  3. customseparate the phases
  4. customseparate the layers
  5. concentrationCombine the organic phases and concentrate under vacuum to about 25 mL
  6. customto give a solid
  7. temperatureCool to ambient temperature
  8. stirringstir for no longer than 2 hours
  9. customcollect the solid
  10. filtrationby filtration
  11. customdry under vacuum overnight

Sources & evidence

ORD record
ord-38273cf3eee440bda4724f1e4a681d64
Source dataset
uspto-grants-2013_05
Patent number
US08436200B2

Reaction notes

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