Anisole → HCID 57422418, compound

HRID 1686278Notes

Reaction equation

HRID 1686278 reaction equation
[CH2:1]([N:8]1[CH2:13][N:12](CC2C=CC(OC)=CC=2OC)[CH2:11][N:10]([C:25]2[CH:26]=[N:27][N:28]([CH2:30][C:31]3[C:32]([CH3:37])=[N:33][O:34][C:35]=3[CH3:36])[CH:29]=2)[C:9]1=[O:38])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O.ClCCl>ClCCl>[CH2:1]([N:8]1[CH2:13][NH:12][CH2:11][N:10]([C:25]2[CH:26]=[N:27][N:28]([CH2:30][C:31]3[C:32]([CH3:37])=[N:33][O:34][C:35]=3[CH3:36])[CH:29]=2)[C:9]1=[O:38])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 7519AnisoleHCID 21863450Trifluoroacetic acid methylene chlorideHCID 57422419HCID 57422419, compound

Product 1

HCID 57422418HCID 57422418, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-benzyl-5-(2,4-dimethoxybenzyl)-3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1,3,5-triazinan-2-one (example 9-6a) (44 mg, 0.09 mmol), anisole (9 mg, 0.09 mmol), and 50% trifluoroacetic acid/dichloromethane solution (1 mL) in dichloromethane (1 mL) were stirred at room temperature for 2 hours. The reaction was concentrated, quenched with saturated sodium bicarbonate (50 mL), extracted with ethyl acetate (2×, 50 mL) and washed with brine (50 mL). The combined organic extracts were dried over magnesium sulfate, filtered and concentrated. Purification by silica column chromatography (100% to 90% dichloromethane in methanol:30 minute gradient) afforded 1-benzyl-3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1,3,5-triazinan-2-one (19 mg, 62%) as a white solid. LC/MS; [M+H] calculated for C19H22N6O2; expected 367.18. found 367.20. The title compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 5.84 μM.

Workup

  1. concentrationThe reaction was concentrated
  2. customquenched with saturated sodium bicarbonate (50 mL)
  3. extractionextracted with ethyl acetate (2×, 50 mL)
  4. washwashed with brine (50 mL)
  5. dry with materialThe combined organic extracts were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica column chromatography (100% to 90% dichloromethane in methanol:30 minute gradient)

Sources & evidence

ORD record
ord-f30b78236544435d9f7cd77458f917df
Source dataset
uspto-grants-2012_04
Patent number
US08148544B2

Reaction notes

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