Triethylamine → HCID 57422460, compound

HRID 1686320Notes

Reaction equation

HRID 1686320 reaction equation
[CH3:1][C:2]1[C:6]([CH2:7][N:8]2[CH:12]=[C:11]([NH2:13])[N:10]=[CH:9]2)=[C:5]([CH3:14])[O:4][N:3]=1.[O:15]1[C:19]2[CH:20]=[CH:21][C:22]([C:24](Cl)=[O:25])=[CH:23][C:18]=2[O:17][CH2:16]1.C(N(CC)CC)C>ClCCl>[CH3:1][C:2]1[C:6]([CH2:7][N:8]2[CH:12]=[C:11]([NH:13][C:24]([C:22]3[CH:21]=[CH:20][C:19]4[O:15][CH2:16][O:17][C:18]=4[CH:23]=3)=[O:25])[N:10]=[CH:9]2)=[C:5]([CH3:14])[O:4][N:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27347491,3-Benzodioxole-5-carbonyl chlorideHCID 57422461HCID 57422461, compound

Product 1

HCID 57422460HCID 57422460, compoundYield 16.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-imidazol-4-amine (example 10-40a) (110 mg, 0.57 mmol), benzo[d][1,3]dioxole-5-carbonyl chloride (105 mg, 0.57 mmol), and triethylamine (90 μL, 0.69 mmol) in dichloromethane was stirred for 16 hours. The reaction was diluted with dichloromethane (30 mL) and washed consecutively with brine and water. The organics were dried over sodium sulfate and concentrated by rotary evaporation. The crude product was purified by reverse phase HPLC (Solvent system:acetonitrile/water, 10% to 100% gradient, 25 minute run) to afford N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-imidazol-4-yl)benzo[d][1,3]dioxole-5-carboxamide as a white crystalline solid (32 mg, 15% yield). MS M+H calculated 341.3. found 341.3. 1H NMR (400 MHz, DMSO-d6): δ 2.08 (s, 3H), 2.41 (s, 3H), 5.02 (s, 2H), 6.07 (s, 2H), 6.95 (d, J=8.4 Hz, 1H), 7.27 (d, J=1.6 Hz, 1H), 7.54 (m, 3H), 10.6 (s, 1H). The compound had an IC50 on hT2R8 bitter receptor of 12.1 μM.

Workup

  1. washwashed consecutively with brine and water
  2. dry with materialThe organics were dried over sodium sulfate
  3. concentrationconcentrated by rotary evaporation
  4. customThe crude product was purified by reverse phase HPLC (Solvent system:acetonitrile/water, 10% to 100% gradient, 25 minute run)

Sources & evidence

ORD record
ord-eec37de7f23a498398698ecf3f72a670
Source dataset
uspto-grants-2012_04
Patent number
US08148544B2

Reaction notes

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