반응 #635324

반응 방정식

1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-imidazol-4-amine

benzo[d][1,3]dioxole-5-carbonyl chloride

triethylamine

→

N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-imidazol-4-yl)benzo[d][1,3]dioxole-5-carboxamide

수율 16.5%

용매

dichloromethane

dichloromethane

반응 조건

후처리

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

실험 절차

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.

출처