Cesium carbonate → HCID 118208529, compound

HRID 595335Notes

Reaction equation

HRID 595335 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].I[CH:8]([CH:10]1[O:14][C:13](=[O:15])[NH:12][CH2:11]1)[CH3:9].[F:16][CH:17]([F:37])[C:18]1[CH:23]=[CH:22][N:21]=[C:20]([NH:24][C:25]2[CH:30]=[C:29]([CH3:31])[CH:28]=[C:27]([C:32]3[CH:33]=[N:34][NH:35][CH:36]=3)[N:26]=2)[CH:19]=1>CN(C=O)C.[Cl-].[Na+].O>[F:37][CH:17]([F:16])[C:18]1[CH:23]=[CH:22][N:21]=[C:20]([NH:24][C:25]2[N:26]=[C:27]([C:32]3[CH:36]=[N:35][N:34]([C:10]4([CH2:8][CH3:9])[O:14][C:13](=[O:15])[NH:12][CH2:11]4)[CH:33]=3)[CH:28]=[C:29]([CH3:31])[CH:30]=2)[CH:19]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 118208464HCID 118208464, compoundHCID 118208630HCID 118208630, compound

Product 1

HCID 118208529HCID 118208529, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

Cesium carbonate (320 mg, 0.99 mmol) and 5-(1-iodoethyl)-1,3-oxazolidin-2-one (160 mg, 0.66 mmol) were added to a solution of N-[4-(difluoromethyl)pyridin-2-yl]-4-methyl-6-(1H-pyrazol-4-yl)pyridin-2-amine (100 mg, 0.33 mmol) in DMF (1 mL) under a nitrogen atmosphere at 20° C. The mixture was stirred under nitrogen and heated to 80° C. for 12 hours. The reaction mixture was cooled to 20° C. and then diluted with brine (50 mL) and extracted with ethyl acetate (3×50 mL). The organic layers were combined, dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford the crude product residue. The crude product residue was purified by prep-TLC (ethyl acetate) to afford racemic 5-[4-(6-{[4-(difluoromethyl)pyridin-2-yl]amino}-4-methylpyridin-2-yl)-1H-pyrazol-1-yl]-5-ethyl-1,3-oxazolidin-2-one. MS ESI calc'd. for C20H21F2N6O2 [M+H]+ 415. found 415. Racemic 5-[4-(6-{[4-(difluoromethyl)pyridin-2-yl]amino}-4-methylpyridin-2-yl)-1H-pyrazol-1-yl]-5-ethyl-1,3-oxazolidin-2-one was separated by SFC (Chiralpak AD, 3 um particle size; 60% [ethanol with 0.05% diethylamine] in CO2) to afford:

Workup

  1. temperatureThe reaction mixture was cooled to 20° C.
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto afford the crude product residue
  7. customThe crude product residue was purified by prep-TLC (ethyl acetate)

Sources & evidence

ORD record
ord-437224ae561844f0b8f1dd9eff3e3860
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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