Isocyanatocarbonyl chloride → HCID 57422422, compound

HRID 548103Notes

Reaction equation

HRID 548103 reaction equation
[CH3:1][C:2]1[C:6]([CH2:7][N:8]2[CH:12]=[C:11]([NH:13][C:14]([NH:16][CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:15])[CH:10]=[N:9]2)=[C:5]([CH3:25])[O:4][N:3]=1.[C:26](=[O:31])=[N:27][C:28](Cl)=[O:29]>C1COCC1>[CH3:1][C:2]1[C:6]([CH2:7][N:8]2[CH:12]=[C:11]([N:13]3[C:28](=[O:29])[NH:27][C:26](=[O:31])[N:16]([CH2:17][CH2:18][C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)[C:14]3=[O:15])[CH:10]=[N:9]2)=[C:5]([CH3:25])[O:4][N:3]=1

Participants

4

Reactant 2

HCID 119708Isocyanatocarbonyl chlorideHCID 57422421HCID 57422421, compound

Product 1

HCID 57422422HCID 57422422, compoundYield 84.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-3-phenethylurea (example 9-7a) (100 mg, 0.29 mmol) in THF (2 mL) was cooled to 0° C. and n-chlorocarbonyl isocyanate (93 mg, 0.88 mmol) was slowly added. After addition, the reaction was allowed to warm 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-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-3-phenethyl-1,3,5-triazinane-2,4,6-trione (100 mg, 83%) as a white solid. 1H NMR (DMSO-d6, 400 MHz): δ2.13 (s, 3H), 2.39 (s, 3H), 2.82 (t, J=5.8 Hz, 2H), 3.88 (t, J=8.0 Hz, 2H), 5.17 (s, 2H), 7.19-7.31 (m, 5H), 7.44 (s, 1H), 7.89 (s, 1H), 11.84 (s, 1H). LC/MS; [M+H] calculated for C20H20N6O4; expected 409.15; found 409.20. The title compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 3.03 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-9120da706ec24114b00546c5a9945a2a
Source dataset
uspto-grants-2011_05
Patent number
US07939671B2

Reaction notes

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