Isocyanatocarbonyl chloride → 1-benzyl-3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1,3,5-triazinane-2,4,6-trione

HRID 548104Notes

Reaction equation

HRID 548104 reaction equation
[CH2:1]([NH:8][C:9]([NH:11][C:12]1[CH:13]=[N:14][N:15]([CH2:17][C:18]2[C:19]([CH3:24])=[N:20][O:21][C:22]=2[CH3:23])[CH:16]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:25](=[O:30])=[N:26][C:27](Cl)=[O:28]>C1COCC1>[CH2:1]([N:8]1[C:27](=[O:28])[NH:26][C:25](=[O:30])[N:11]([C:12]2[CH:13]=[N:14][N:15]([CH2:17][C:18]3[C:19]([CH3:24])=[N:20][O:21][C:22]=3[CH3:23])[CH:16]=2)[C:9]1=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 119708Isocyanatocarbonyl chlorideHCID 574224201-benzyl-3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)urea

Product 1

HCID 574224231-benzyl-3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1,3,5-triazinane-2,4,6-trioneYield 93%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1-benzyl-3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)urea (example 95b) (100 mg, 0.31 mmol) in THF (2 mL) was cooled to 0° C. and n-chlorocarbonyl isocyanate (97 mg, 0.92 mmol) was slowly added. After addition, the reaction was allowed to warm up to room temperature and stirred for 1 hour. The reaction was concentrated and the residue was purified by silica column chromatography (100% to 90% dichloromethane in methanol:30 minute gradient) to afford 1-benzyl-3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-1,3,5-triazinane-2,4,6-trione (112 mg, 93%) as a white solid. 1H NMR (DMSO-d6, 400 MHz): δ2.12 (s, 3H), 2.38 (s, 3H), 4.87 (s, 2H), 5.16 (s, 2H), 7.23-7.34 (m, 5H), 7.45 (s, 1H), 7.90 (s, 1H), 11.93 (s, 1H). LC/MS; [M+H] calculated for C19H18N6O4; expected 395.14; found 395.15. The title compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 1.14 μM.

Workup

  1. additionAfter addition
  2. concentrationThe reaction was concentrated
  3. customthe residue was purified by silica column chromatography (100% to 90% dichloromethane in methanol:30 minute gradient)

Sources & evidence

ORD record
ord-f00ec794e9ef48a29816c6de10d67f58
Source dataset
uspto-grants-2011_05
Patent number
US07939671B2

Reaction notes

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