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 1770505Notes

Reaction equation

HRID 1770505 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 chromotography (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 chromotography (100% to 90% dichloromethane in methanol: 30 minute gradient)

Sources & evidence

ORD record
ord-c158329533f64abdaf93e1d00c190f01
Source dataset
uspto-grants-2016_02
Patent number
US09247759B2

Reaction notes

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