Triethylamine → HCID 57422499, compound

HRID 658757Notes

Reaction equation

HRID 658757 reaction equation
[CH3:1][C:2]1[C:6]([CH2:7][N:8]2[CH:12]=[C:11]([N:13]3[C:17](=[O:18])[CH2:16][NH:15][C:14]3=[O:19])[CH:10]=[N:9]2)=[C:5]([CH3:20])[O:4][N:3]=1.Cl.[CH3:22][O:23]C(=O)[C@H](CO)N.C(N(CC)CC)C>C1(C)C=CC=CC=1>[CH3:1][C:2]1[C:6]([CH2:7][N:8]2[CH:12]=[C:11]([N:13]3[C:17](=[O:18])[CH:16]([CH2:22][OH:23])[NH:15][C:14]3=[O:19])[CH:10]=[N:9]2)=[C:5]([CH3:20])[O:4][N:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2723730L-Serine, methyl ester, hydrochloride (1:1)HCID 574224243-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)imidazolidine-2,4-dione

Product 1

HCID 57422499HCID 57422499, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

4-((4-isocyanato-1H-pyrazol-1-yl)methyl)-3,5-dimethylisoxazole (example 10-1) (784 mg, 3.6 mmol), serine methyl ester hydrochoride (672 mg, 4.32 mmol) and triethylamine (1 mL, 7.2 mmol) were refluxed in toluene (16 mL) for 8 hours. The reaction was allowed to cool to room temperature and then the solution was concentrated on the rotovap. The product was purified by reverse phase HPLC (5 to 95% acetonitrile in H2O: 16 minute gradient) to afford 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-5-(hydroxymethyl)imidazolidine-2,4-dione as a white solid (60 mg, 25%). 1H NMR (CDCl3, 400 MHz): δ(s, 3H), 2.40 (s, 3H), 3.13-3.07 (m, 1H), 3.94-3.93 (d, J=4 Hz, 2H), 4.21-4.19 (t, J=4 Hz, 1H), 5.03 (s, 2H), 6.68 (bs, 1H), 7.87 (s, 1H), 7.99 (s, 1H). The title compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 3 μM.

Workup

  1. concentrationthe solution was concentrated on the rotovap
  2. customThe product was purified by reverse phase HPLC (5 to 95% acetonitrile in H2O: 16 minute gradient)

Sources & evidence

ORD record
ord-ad5c7ca887ee4981b0ec958f42a19204
Source dataset
uspto-grants-2011_12
Patent number
US08076491B2

Reaction notes

Loading…