Potassium Carbonate → 4-((3-cyclopropyl-4-nitro-1H-indazol-1-yl)methyl)-2-methyloxazole

HRID 79462Notes

Reaction equation

HRID 79462 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[N+:11]([O-:13])=[O:12])[N:4]([CH2:14][C:15]2[N:16]=[C:17]([CH3:20])[O:18][CH:19]=2)[N:3]=1.[CH:21]1(B(O)O)[CH2:23][CH2:22]1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=C(S([O-])(=O)=O)C=2OC)CCCCC1.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[CH:21]1([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][C:9]=3[N+:11]([O-:13])=[O:12])[N:4]([CH2:14][C:15]3[N:16]=[C:17]([CH3:20])[O:18][CH:19]=3)[N:3]=2)[CH2:23][CH2:22]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 2760897Cyclopropylboronic acidHCID 23677046Sodium 2'-(dicyclohexylphosphino)-2,6-dimethoxybiphenyl-3-sulfonateHCID 672615694-((3-bromo-4-nitro-1H-indazol-1-yl)methyl)-2-methyloxazole

Product 1

HCID 672613544-((3-cyclopropyl-4-nitro-1H-indazol-1-yl)methyl)-2-methyloxazoleYield 32.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

A 25 mL round bottom flask equipped with a reflux condenser and a nitrogen line was charged with 4-((3-bromo-4-nitro-1H-indazol-1-yl)methyl)-2-methyloxazole (304 mg, 0.902 mmol), cyclopropylboronic acid (170 mg, 1.98 mmol), palladium acetate (8 mg, 0.036 mmol), potassium carbonate (410 mg, 2.98 mmol), and sodium 2′-(dicyclohexylphosphino)-2,6-dimethoxybiphenyl-3-sulfonate (37 mg, 0.072 mmol). To the flask was added a 1,4-dioxane:water mixture (5:1; 6 mL), and the flask was evacuated and refilled with nitrogen three times. The reaction mixture was stirred and heated at reflux for 11 hours. The reaction mixture was cooled, diluted with excess water and extracted multiple times with DCM and EtOAc. The combined organic extracts were dried over anhydrous sodium sulfate, concentrated, and subjected to preparative thin-layer chromatography (silica, 1:1 EtOAc/Hexane as eluent) to afford the product (88.1 mg) as a solid.

Workup

  1. customA 25 mL round bottom flask equipped with a reflux condenser
  2. customwater mixture (5:1; 6 mL), and the flask was evacuated
  3. additionrefilled with nitrogen three times
  4. temperatureheated
  5. temperatureat reflux for 11 hours
  6. temperatureThe reaction mixture was cooled
  7. additiondiluted with excess water
  8. extractionextracted multiple times with DCM and EtOAc
  9. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-01d5f98f6c434ee2a71eb0effdb1885a
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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