Triethylamine → HCID 57422414, compound

HRID 2094944Notes

Reaction equation

HRID 2094944 reaction equation
Cl.[CH3:2][C:3]1[C:7]([CH2:8][N:9]2[CH:13]=[C:12]([NH2:14])[CH:11]=[N:10]2)=[C:6]([CH3:15])[O:5][N:4]=1.[N:16]([C:19]1[CH:28]=[CH:27][CH:26]=[CH:25][C:20]=1[C:21](OC)=[O:22])=[C:17]=[O:18].C(N(CC)CC)C>C(#N)C.O>[CH3:2][C:3]1[C:7]([CH2:8][N:9]2[CH:13]=[C:12]([N:14]3[C:21](=[O:22])[C:20]4[C:19](=[CH:28][CH:27]=[CH:26][CH:25]=4)[NH:16][C:17]3=[O:18])[CH:11]=[N:10]2)=[C:6]([CH3:15])[O:5][N:4]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 519494Methyl 2-isocyanatobenzoateHCID 574222641-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride

Product 1

HCID 57422414HCID 57422414, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride (75 mg, 0.33 mmol), methyl 2-isocyanatobenzoate, and triethylamine (200 mg, 2 mmol) in acetonitrile (3 mL) were irradiated in the microwave reactor at 100° C. for 30 minutes. The reaction was cooled, diluted with H2O (75 mL), and extracted with ethyl acetate (3×, 50 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated on the rotovap. The residue was purified by silica gel chromotography (75% ethyl acetate in hexanes) to afford 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)quinazoline-2,4(1H,3H)-dione (20 mg, 18%) as a light pink solid. 1H NMR (DMSO-d6, 400 MHz): δ2.16 (s, 3H), 2.40 (s, 3H), 5.17 (s, 2H), 7.17-7.22 (m, 2H), 7.50 (s, 1H), 7.66 (dt, J=8, 1.2 Hz, 1H), 7.92 (d, J=6.8 Hz, 1H), 7.95 (s, 1H), 11.52 (bs, 1H). The title compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 1.5 μM.

Workup

  1. temperatureThe reaction was cooled
  2. extractionextracted with ethyl acetate (3×, 50 mL)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated on the rotovap
  6. customThe residue was purified by silica gel chromotography (75% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-a9521f30b0ae4ca1a60bfa5b4c337028
Source dataset
uspto-grants-2013_05
Patent number
US08445692B2

Reaction notes

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