Pyridine → HCID 59252424, compound

HRID 42305Notes

Reaction equation

HRID 42305 reaction equation
O=[C:2]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:3][NH:4][C:5]([C:7]1[CH:8]=[N:9][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:11][CH:12]=1)=[O:6].N1C=CC=CC=1.C(=O)(O)[O-].[Na+]>O=P(Cl)(Cl)Cl.C(OCC)(=O)C>[C:19]1([C:2]2[O:6][C:5]([C:7]3[CH:8]=[N:9][C:10]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)=[N:11][CH:12]=3)=[N:4][CH:3]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 516892Sodium BicarbonateHCID 59252375HCID 59252375, compound

Product 1

HCID 59252424HCID 59252424, compoundYield 65.5%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 24813Phosphorus oxychlorideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution consisting of N-(2-oxo-2-phenylethyl)-2-phenylpyrimidine-5-carboxamide (Step A, 80 mg, 0.25 mmol) in POCl3 (1.0 mL) was added pyridine (2.0 mL). The solution was heated at 70° C. for six hours and was subsequently allowed to cool to room temperature. The solution was diluted with ethyl acetate (10 mL) and poured into a chilled saturated aqueous sodium bicarbonate solution (40 mL). After stirring for 15 minutes, the mixture was extracted with ethyl acetate (3×25 mL) and the combined organics were dried with anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by silica gel flash chromatography (0-5% methanol in dichloromethane gradient) through a 40-g Silicycle® flash silica cartridge to afford the title compound as an off-white solid (49 mg, 65% yield); Rf 0.80 with 2% methanol in dichloromethane; 1H-NMR (300 MHz; DMSO-d6) δ 9.52 (s, 2H), 8.48 (dd, 2H), 7.99 (s, 1H), 7.94 (dd, 2H), 7.43-7.60 (m, 6H); MS (ESI+) m/z 300 (M+1); H-PGDS FPBA IC50: >20 μM.

Workup

  1. temperatureto cool to room temperature
  2. extractionthe mixture was extracted with ethyl acetate (3×25 mL)
  3. dry with materialthe combined organics were dried with anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel flash chromatography (0-5% methanol in dichloromethane gradient) through a 40-g Silicycle® flash silica cartridge

Sources & evidence

ORD record
ord-a506e9372945452380a6b7796aae62a9
Source dataset
uspto-grants-2013_09
Patent number
US08536185B2

Reaction notes

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