Acetic Acid → HCID 9926463, compound

HRID 915578Notes

Reaction equation

HRID 915578 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].C(=O)([O-])[O-].[K+].[K+].[NH2:19][C:20]1[N:24]([CH3:25])[N:23]=[C:22]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:21]=1.C(O)(=O)C>CN(C=O)C.O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[C:26]([C:22]1[CH:21]=[C:20]([NH:19][C:2]2[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:3]=2[C:4]([OH:6])=[O:5])[N:24]([CH3:25])[N:23]=1)([CH3:29])([CH3:27])[CH3:28]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 899062-Bromo-5-methoxybenzoic acidHCID 27352873-tert-Butyl-1-methyl-1H-pyrazol-5-amine

Product 1

HCID 9926463HCID 9926463, compoundYield 32.8%

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 2-bromo-5-methoxy benzoic acid (2.26 g, 9.79 mmol), potassium carbonate (1.49 g, 10.8 mmol), 5-amino-3-tert-butyl-1-methylpyrazole (1.50 g, 9.79 mmol), and copper (II) acetate (35 mg, 0.20 mmol) in DMF (20 mL) was heated (150° C.) in a sealed tube for 16 h. After cooling, the reaction mixture was diluted with water (10 mL) and acidified to pH=4 with acetic acid. This mixture was extracted with dichloromethane (3×20 mL), and then the combined organic extracts were washed with water (2×30 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. HPLC purification of the residue (YMC propack C18 column, 150×20 mm ID, 30%-80% acetonitrile in water gradient) afforded the title compound (973 mg, 31%) as a pale yellow solid. 1H NMR (300 MHz, DMSO-d6) δ 13.22 (br s, 1H), 9.24 (br s, 1H), 7.38 (d, 1H), 7.10 (dd, 1H), 6.80 (d, 1H), 5.95 (s, 1H), 3.70 (s, 3H), 3.55 (s, 3H), 1.21 (s, 9H); ES-MS m/z 304.2 (MH+), HPLC RT (min) 2.58.

Workup

  1. temperatureAfter cooling
  2. extractionThis mixture was extracted with dichloromethane (3×20 mL)
  3. washthe combined organic extracts were washed with water (2×30 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customHPLC purification of the residue (YMC propack C18 column, 150×20 mm ID, 30%-80% acetonitrile in water gradient)

Sources & evidence

ORD record
ord-0339496d3f8b4ff3886f1c78ef57572f
Source dataset
uspto-grants-2007_09
Patent number
US07265144B2

Reaction notes

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