Cesium carbonate → HCID 86703440, compound

HRID 1909307Notes

Reaction equation

HRID 1909307 reaction equation
[CH:1]1([N:6]2[C:14]3[CH:13]=[C:12](B4OC(C)(C)C(C)(C)O4)[CH:11]=[C:10]([C:24]([NH:26][CH2:27][C:28]4[C:29](=[O:36])[NH:30][C:31]([CH3:35])=[CH:32][C:33]=4[CH3:34])=[O:25])[C:9]=3[CH:8]=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.Br[C:38]1[CH:45]=[CH:44][C:41]([CH:42]=[O:43])=[CH:40][N:39]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:1]1([N:6]2[C:14]3[CH:13]=[C:12]([C:38]4[CH:45]=[CH:44][C:41]([CH:42]=[O:43])=[CH:40][N:39]=4)[CH:11]=[C:10]([C:24]([NH:26][CH2:27][C:28]4[C:29](=[O:36])[NH:30][C:31]([CH3:35])=[CH:32][C:33]=4[CH3:34])=[O:25])[C:9]=3[CH:8]=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 117692346-Bromo-3-pyridinecarboxaldehydeHCID 68295075HCID 68295075, compound

Product 1

HCID 86703440HCID 86703440, compoundYield 45.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 1-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole-4-carboxamide (0.15 g, 0.31 mmol) and 6-bromonicotinaldehyde (0.047 g, 0.25 mmol) in dioxane/water mixture (2 mL+0.5 mL), Cs2CO3 (0.219 g, 0.239 mmol) was added and solution purged with argon for 15 min. Then Pd(PPh3)4 (0.031 g, 0.025 mmol) was added and argon was purged again for 10 min. Reaction mixture was heated at 100° C. for 2 h. On completion, reaction mixture was diluted with water and extracted with 10% MeOH/DCM. Combined organic layers were dried over Na2SO4 and solvent removed under reduced pressure to afford crude material which was purified by column chromatography over silica gel to afford 1-cyclopentyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-6-(5-formylpyridin-2-yl)-1H-indazole-4-carboxamide (0.053 g, 37%).

Workup

  1. customsolution purged with argon for 15 min
  2. customargon was purged again for 10 min
  3. customReaction mixture
  4. customOn completion, reaction mixture
  5. extractionextracted with 10% MeOH/DCM
  6. dry with materialCombined organic layers were dried over Na2SO4 and solvent
  7. customremoved under reduced pressure
  8. customto afford crude material which
  9. customwas purified by column chromatography over silica gel

Sources & evidence

ORD record
ord-7f29f6a345ee4e4eb59ed2e12ff61bfb
Source dataset
uspto-grants-2013_12
Patent number
US08598167B1

Reaction notes

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