Hydrochloric Acid → HCID 178428490, compound

HRID 2189159Notes

Reaction equation

HRID 2189159 reaction equation
[OH-].[K+].[CH3:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([CH:13]=O)[CH:11]=2)[NH:6][N:5]=1.[C:15]([C:18]1[CH:23]=[CH:22][C:21]([NH:24]C(=O)C)=[CH:20][C:19]=1[CH3:28])(=[O:17])[CH3:16].Cl.C([O-])(O)=O.[Na+]>C(O)C>[NH2:24][C:21]1[CH:22]=[CH:23][C:18]([C:15](=[O:17])/[CH:16]=[CH:13]/[C:10]2[CH:11]=[C:12]3[C:7](=[CH:8][CH:9]=2)[NH:6][N:5]=[C:4]3[CH3:3])=[C:19]([CH3:28])[CH:20]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 516892Sodium BicarbonateHCID 2737381N-(4-Acetyl-3-methylphenyl)acetamideHCID 178434286HCID 178434286, compound

Product 1

HCID 178428490HCID 178428490, compoundYield 32.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of KOH (1.5 g, 26 mmol) in 20 mL ethanol were added 3-methyl-1H-indazole-5-carbaldehyde (see Note 1 for synthesis) (0.850 g, 5.3 mmol) and commercially available N-(4-acetyl-3-methylphenyl)acetamide (1.0 g, 5.3 mmol). The reaction mixture was heated to 80° C. for 24 hours and then cooled down to room temperature. After acidification with 1N HCl, the mixture was brought to pH 8 with saturated aqueous NaHCO3 and extracted twice with ethyl acetate (2×100 mL). The combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The product was purified by SiO2 flash chromatography (60:40 to 50:50 hexanes/ethyl acetate) to afford (E)-1-(4-amino-2-methylphenyl)-3-(3-methyl-1H-indazol-5-yl)prop-2-en-1-one (0.500 g, 32%). 1H NMR (400 MHz, d6-DMSO): δ 12.8 (s, 1H), 8.12 (s, 1H), 7.81 (dd, 1H), 7.78 (d, 1H), 7.61 (d, 2H), 7.48 (d, 1H), 6.45 (m, 2H), 5.88 (br s, 1H), 3.06 (s, 3H), 2.42 (s, 3H); MS (EI) for C18H17N3O: 292.3 (MH+).

Workup

  1. temperaturecooled down to room temperature
  2. extractionextracted twice with ethyl acetate (2×100 mL)
  3. washThe combined organic phases were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe product was purified by SiO2 flash chromatography (60:40 to 50:50 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-825ff4a1005a4bcf93d293ecd3e71c04
Source dataset
uspto-grants-2012_12
Patent number
US08324231B2

Reaction notes

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