Sodium Bicarbonate → HCID 178515680, compound

HRID 510428Notes

Reaction equation

HRID 510428 reaction equation
[Cl:1][C:2]1[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:3]=1[CH2:4][C:5]1[C:6]([C:11]([F:14])([F:13])[F:12])=[N:7][NH:8][C:9]=1[NH2:10].O=[C:21]([C:28]1[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=1)[CH2:22][C:23](OCC)=[O:24].C(=O)(O)[O-].[Na+]>OS(O)(=O)=O.O1CCOCC1>[Cl:1][C:2]1[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][C:3]=1[CH2:4][C:5]1[C:6]([C:11]([F:13])([F:14])[F:12])=[N:7][N:8]2[C:23]([OH:24])=[CH:22][C:21]([C:28]3[CH:33]=[CH:32][N:31]=[CH:30][CH:29]=3)=[N:10][C:9]=12

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 2735202Ethyl 3-(4-pyridyl)-3-oxopropionateHCID 178509121HCID 178509121, compound

Product 1

HCID 178515680HCID 178515680, compoundYield 10%

Reagents, catalysts & solvents 2

HCID 1118Sulfuric AcidSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4-(2,3-dichlorobenzyl)-3-(trifluoromethyl)-1H-pyrazol-5-amine (100 mg, 0.332 mmol), ethyl 3-oxo-3-(pyridin-4-yl)propanoate (75 mg, 0.387 mmol) in conc. H2SO4 (1.5 mL) and dioxane (15 mL) was placed in a sealed tube and stirred at 120° C. for 16 h. After cooled to room temperature, the pH of the mixture was carefully adjusted to 8 with saturated aq. sodium bicarbonate solution. The resulting mixture was extracted with DCM (50 mL×3). The combined organic layers were washed with water and brine, dried over sodium sulphate, filtered and concentrated. The residue was purified by silica gel column and reverse-phase Prep-HPLC to give the title product (14 mg, 10%) as a yellow solid; LC/MS: MS (ES+) m/e 439 (MH+); 1H NMR (300 MHz, DMSO-d6) δ ppm 4.29 (s, 2H), 6.35 (s, 1H), 6.89 (dd, J=1.2, 7.8 Hz, 1H), 7.23 (t, J=7.8 Hz, 1H), 7.52 (dd, J=1.2, 7.8 Hz, 1H), 7.83 (d, J=6.0 Hz, 2H), 8.80 (d, J=6.0 Hz, 2H), 12.81 (s, 1H).

Workup

  1. customwas placed in a sealed tube
  2. temperatureAfter cooled to room temperature
  3. extractionThe resulting mixture was extracted with DCM (50 mL×3)
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel column and reverse-phase Prep-HPLC

Sources & evidence

ORD record
ord-a3485a2df7b744149cf88e49e509fecb
Source dataset
uspto-grants-2015_08
Patent number
US09096605B2

Reaction notes

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