Cesium carbonate → HCID 117843511, compound

HRID 2209065Notes

Reaction equation

HRID 2209065 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[N:16]=[C:15]([O:17][C@@H:18]([C@H:20]3[CH2:24][NH:23][C:22](=[O:25])[CH2:21]3)[CH3:19])[C:14]3[NH:26][CH:27]=[N:28][C:13]=3[CH:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].C([O-])([O-])=O.[Cs+].[Cs+].FC(F)(F)S(O[CH2:41][CH:42]([F:44])[F:43])(=O)=O>CN(C=O)C.CCOC(C)=O.O.[Cl-].[Na+].O>[F:43][CH:42]([F:44])[CH2:41][N:26]1[C:14]2[C:15]([O:17][C@@H:18]([C@H:20]3[CH2:24][NH:23][C:22](=[O:25])[CH2:21]3)[CH3:19])=[N:16][C:11]([C:5]3[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=3)=[CH:12][C:13]=2[N:28]=[CH:27]1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 27740892,2-Difluoroethyl trifluoromethanesulfonate2×HCID 178488441HCID 178488441, compound

Product 1

HCID 117843511HCID 117843511, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of crude (R)-4-((R)-1-(6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one 3.09 (ca. 0.13 mmol) in DMF (1 mL) was added Cs2CO3 (114 mg, 0.35 mmol) followed by 2,2-difluoroethyl trifluoromethanesulfonate (36 mg, 0.17 mmol). After 40 min, an additional portion of 2,2-difluoroethyl trifluoromethanesulfonate (7 mg, 0.03 mmol) was added. After an additional 30 min, the reaction mixture was diluted with EtOAc (20 mL), water (10 mL), and brine (10 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (20 mL). The combined organic phase was dried over Na2SO4, filtered, and concentrated. The crude product was purified by silica gel chromatography (0% to 10% MeOH in DCM) to afford (R)-4-((R)-1-(3-(2,2-difluoroethyl)-6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one 3.12.

Workup

  1. waitAfter an additional 30 min
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with EtOAc (20 mL)
  4. dry with materialThe combined organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel chromatography (0% to 10% MeOH in DCM)

Sources & evidence

ORD record
ord-d69e251246924c7ab1e51c3f359d78a8
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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