反应 #1857596

反应方程式

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

3-methoxybenzoic acid

EDC

triethyl amine

→

N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-3-methoxybenzamide

收率 43.6%

溶剂

DCM

DCM

反应条件

后处理

1. 1
   洗涤the organic phase was washed with aqueous 0.1 N HCL (150 mL)
2. 2
   干燥The organic layer was dried over sodium sulfate
3. 3
   过滤filtered
4. 4
   浓缩concentrated on the rotovap
5. 5
   其他The crude product was purified by silica gel chromotography (40% ethyl acetate in hexanes)
6. 6
   其他to afford 225 mg of an off white solid
7. 7
   其他The solid was triturated with ethyl acetate/hexanes (1/9)
8. 8
   过滤the white solid was collect by filtration
9. 9
   workup.DISSOLUTIONThe pure product was dissolved in absolute ethanol
10. 10
    浓缩concentrated on the rotovap (4×, 25 mL)

实验过程

1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-amine hydrochloride (Example 4-1a) (300 mg, 1.3 mmol), 3-methoxybenzoic acid (172 mg, 1.3 mmol), EDC (386 mg, 2 mmol), and triethyl amine (303 mg, 3 mmol) were stirred in DCM (5 mL) at ambient temperature for 6 hours. The reaction was diluted with DCM (50 mL) and the organic phase was washed with aqueous 0.1 N HCL (150 mL) followed by aqueous 1N NaOH (150 mL). The organic layer was dried over sodium sulfate, filtered and concentrated on the rotovap. The crude product was purified by silica gel chromotography (40% ethyl acetate in hexanes) to afford 225 mg of an off white solid. The solid was triturated with ethyl acetate/hexanes (1/9) and the white solid was collect by filtration. The pure product was dissolved in absolute ethanol and concentrated on the rotovap (4×, 25 mL) to afford N-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)-3-methoxybenzamide (185 mg, 43%) as a white solid. NMR (CDCl3, 400 MHz): b 2.20 (s, 3H), 2.42 (s, 3H), 3.85 (s, 3H), 5.03 (s, 2H), 7.09-7.06 (m, 1H), 7.37-7.35 (m, 2H), 7.41 (m, 1H), 7.51 (s, 1H), 7.93 (bs, 1H), 8.03 (s, 1H). LC/MS; [M+H] calculated for C17H18N4O3; expected 327.14. Found 327.30. Melting point: 127-129° C.

来源