Carbonate Ion → Methyl 3-(2-chlorophenyl)-1-isopropyl-1H-indazole-6-carboxylate

HRID 1047627Notes

Reaction equation

HRID 1047627 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([O:13][CH3:14])=[O:12])=[CH:8][CH:9]=2)[N:4]([CH:15]([CH3:17])[CH3:16])[N:3]=1.[Cl:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1B(O)O.C(=O)([O-])[O-]>[Cu]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O>[Cl:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([O:13][CH3:14])=[O:12])=[CH:8][CH:9]=2)[N:4]([CH:15]([CH3:17])[CH3:16])[N:3]=1

Participants

8

Reactant 3

HCID 19660Carbonate IonHCID 27343222-Chlorophenylboronic acidHCID 66661453methyl 3-bromo-1-isopropyl-1H-indazole-6-carboxylate

Product 1

HCID 66661389Methyl 3-(2-chlorophenyl)-1-isopropyl-1H-indazole-6-carboxylateYield 31%

Reagents, catalysts & solvents 4

HCID 62652Cuprous chlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of methyl 3-bromo-1-isopropyl-1H-indazole-6-carboxylate (0.32 g, 1.08 mmol), 2-chlorophenylboronic acid (0.51 g, 3.29 mmol), cessium carbonate (1.15 g, 3.52 mmol), copper(I) chloride (0.11 g, 1.09 mmol), 1,1′-bis(diphenylphosphino)ferrocene (61.1 mg, 0.11 mmol) and palladium(II) acetate (12.6 mg, 0.06 mmol) under argon was added N,N-dimethylformamide (4.3 mL). The mixture was stirred in a sealed tube at 90° C. for 18 h. After 18 h, the mixture was cooled to ambient temperature and quenched with saturated aqueous sodium bicarbonate (15 mL). The mixture was extracted with ethyl acetate (3×15 mL). The combined organic layer was washed with saturated aqueous ammonium chloride (4×10 mL), saturated aqueous sodium chloride (1×10 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography (100% hexanes→85% hexanes/ethyl acetate) gave the title compound (0.11 g): LC-MS [M+1]=329.2.

Workup

  1. waitAfter 18 h
  2. temperaturethe mixture was cooled to ambient temperature
  3. customquenched with saturated aqueous sodium bicarbonate (15 mL)
  4. extractionThe mixture was extracted with ethyl acetate (3×15 mL)
  5. washThe combined organic layer was washed with saturated aqueous ammonium chloride (4×10 mL), saturated aqueous sodium chloride (1×10 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification by silica gel chromatography (100% hexanes→85% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-9b8ff0b5b4874b77be4d8ca16df8721c
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

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