Cesium carbonate → HCID 117843002, compound

HRID 2209066Notes

Reaction equation

HRID 2209066 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+].I[CH:36]1[CH2:39][O:38][CH2:37]1>CN(C=O)C.CCOC(C)=O.O.[Cl-].[Na+].O>[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[N:26]([CH:36]4[CH2:39][O:38][CH2:37]4)[CH:27]=[N:28][C:13]=3[CH:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 133566863-Iodooxetane3×HCID 178488441HCID 178488441, compound

Product 1

HCID 117843002HCID 117843002, compound

Reagents, catalysts & solvents 4

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

Conditions

Temperature
60 °C

Procedure

To crude (R)-4-((R)-1-(6-(3,4-dimethoxyphenyl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one 3.09 (0.064 mmol) as a solution in DMF (1 mL) was added Cs2CO3 (52 mg, 0.16 mmol) followed by 3-iodo-oxetane (7.0 μL, 0.078 mmol). After stirring 30 min, the reaction temperature was increased to 60° C. After an additional 40 min, 3-iodo-oxetane (7.0 μL, 0.078 mmol) was added and the reaction temperature was increased to 100° C. After stirring an additional 35 min at 100° C., 3-iodo-oxetane (3.0 μL, 0.034 mmol) was added. After an additional 40 min, the reaction mixture was cooled to r.t. and 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, and the crude product was purified by silica gel chromatography (0% to 10% MeOH in DCM) to afford (R)-4-((R)-1-(6-(3,4-dimethoxyphenyl)-3-(oxetan-3-yl)-3H-imidazo[4,5-c]pyridin-4-yloxy)ethyl)pyrrolidin-2-one 3.14.

Workup

  1. waitAfter an additional 40 min
  2. temperaturethe reaction temperature was increased to 100° C
  3. stirringAfter stirring an additional 35 min at 100° C.
  4. waitAfter an additional 40 min
  5. temperaturethe reaction mixture was cooled to r.t.
  6. customThe phases were separated
  7. extractionthe aqueous phase was extracted with EtOAc (20 mL)
  8. dry with materialThe combined organic phase was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customthe crude product was purified by silica gel chromatography (0% to 10% MeOH in DCM)

Sources & evidence

ORD record
ord-350a29f007854b278e9e6be7953e8034
Source dataset
uspto-grants-2016_06
Patent number
US09376441B2

Reaction notes

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