Potassium Carbonate → 2,2-Dimethyl-propionic acid 7-(2-chloro-3,6-difluoro-phenyl)-5-(2,2,2-trifluoro-ethyl)-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazin-8-yl ester

HRID 1512066Notes

Reaction equation

HRID 1512066 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([F:9])[C:3]=1[C:10]1[C:19](=[O:20])[NH:18][C:13]2=[N:14][CH:15]=[CH:16][N:17]=[C:12]2[C:11]=1[O:21][C:22](=[O:27])[C:23]([CH3:26])([CH3:25])[CH3:24].C(=O)([O-])[O-].[K+].[K+].O([CH2:42][C:43]([F:46])([F:45])[F:44])S(C(F)(F)F)(=O)=O>>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([F:9])[C:3]=1[C:10]1[C:19](=[O:20])[N:18]([CH2:42][C:43]([F:46])([F:45])[F:44])[C:13]2=[N:14][CH:15]=[CH:16][N:17]=[C:12]2[C:11]=1[O:21][C:22](=[O:27])[C:23]([CH3:24])([CH3:26])[CH3:25]

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 579988432,2-Dimethyl-propionic acid 7-(2-chloro-3,6-difluoro-phenyl)-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazin-8-yl ester

Product 1

HCID 593923702,2-Dimethyl-propionic acid 7-(2-chloro-3,6-difluoro-phenyl)-5-(2,2,2-trifluoro-ethyl)-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazin-8-yl ester

Procedure

A mixture of 2,2-dimethyl-propionic acid 7-(2-chloro-3,6-difluoro-phenyl)-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazin-8-yl ester (is this correct or did the reaction start with the unprotected species?) (Example 1.3) (0.10 g), potassium carbonate (0.053 g) and 2,2,2-trifluoroethyl triflate (0.130 g) were heated in a microwave at 150° C. for 30 minutes, and then at 170° C. for 30 minutes. The reaction mixture was allowed to cool to ambient temperature and was then partitioned between dichloromethane and aqueous hydrochloric acid (2M). The phases were separated. The organic layer was dried over magnesium sulfate and concentrated. The residue was dissolved in dichloromethane and treated with trimethylacetyl chloride (0.063 ml) and pyridine (0.061 ml) and stirred at ambient temperature. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel (eluent: acetone/iso-hexane 0:10 to 1:9) to give Compound No. C8 of Table C as a beige solid (0.049 g).

Workup

  1. customwas then partitioned between dichloromethane and aqueous hydrochloric acid (2M)
  2. customThe phases were separated
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in dichloromethane
  6. additiontreated with trimethylacetyl chloride (0.063 ml) and pyridine (0.061 ml)
  7. concentrationThe reaction mixture was concentrated
  8. customthe residue was purified by column chromatography on silica gel (eluent: acetone/iso-hexane 0:10 to 1:9)
  9. customto give Compound No

Sources & evidence

ORD record
ord-fb2e3fb776e7413e92e3a935544c8349
Source dataset
uspto-grants-2012_07
Patent number
US08217055B2

Reaction notes

Loading…