تفاعل #713933

معادلة التفاعل

4-chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine

1-(6-aminopyrimidin-4-yl)-ethanol

Xantphos

cesium carbonate

→

title compound

المردود 21.0%

1-{6-[2-(2,6-Dichlorophenyl)-2H-pyrazolo[4,3-c]pyridin-4-ylamino]-pyrimidin-4-yl}-ethanol

المردود 21.0%

المذيبات

dioxane

ظروف التفاعل

المعالجة

1. 1
   أخرىwas de-gassed
2. 2
   أخرىpurged with nitrogen
3. 3
   ترشيحThe resultant mixture was filtered
4. 4
   غسيلwashed with dioxane
5. 5
   تركيزThe filtrate was concentrated under reduced pressure
6. 6
   أخرىthe resultant residue was purified by silica gel flash chromatography (0-100% ethyl acetate in cyclohexane)
7. 7
   أخرىto afford a yellow solid
8. 8
   أخرىThis was re-purified by HPLC [gradient: 5 to 98% acetonitrile (0.1% ammonium hydroxide) in water (0.1% ammonium hydroxide)]

الإجراء التجريبي

A mixture of 4-chloro-2-(2,6-dichlorophenyl)-2H-pyrazolo[4,3-c]pyridine (133 mg, 0.445 mmol), 1-(6-aminopyrimidin-4-yl)-ethanol (65 mg, 0.467 mmol), Pd2(dba)3 (20 mg, 0.022 mmol), Xantphos (26 mg, 0.045 mmol) and cesium carbonate (290 mg, 0.89 mmol) in dioxane (3.5 mL) was de-gassed and purged with nitrogen and the reaction mixture was heated at 150° C. in the microwave for 30 minutes. The resultant mixture was filtered and washed with dioxane. The filtrate was concentrated under reduced pressure and the resultant residue was purified by silica gel flash chromatography (0-100% ethyl acetate in cyclohexane) to afford a yellow solid. This was re-purified by HPLC [gradient: 5 to 98% acetonitrile (0.1% ammonium hydroxide) in water (0.1% ammonium hydroxide)], to afford the title compound as a white solid (31 mg, 21% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.53 (d, J=0.9 Hz, 1H), 9.07 (d, J=1.1 Hz, 1H), 8.09 (d, J=7.3 Hz, 1H), 7.88-7.86 (m, 2H), 7.78 (dd, J=9.2, 7.1 Hz, 1H), 7.68-7.61 (m, 2H), 4.83-4.76 (m, 1H), 1.46 (d, J=6.7 Hz, 3H). LCMS (Method B): RT=2.74 min, m/z: 401 [M+H+].

المصدر