반응 #1763126

반응 방정식

HCl

KOH

3-methyl-5-pyridylboronic acid

water

cesium carbonate

3-methylpyrazole

NaHMDS

→

title compound ( 5-2 )

5′-methyl-6-(3-methyl-1H-pyrazol-1-yl)-3,3′-bipyridine-5-carboxylic acid

용매

THF

MeOH

dimethylformamide

MeOH

dioxane

diethylether

반응 조건

후처리

1. 1
   기타The system was partitioned between water and EtOAc
2. 2
   건조dried over magnesium sulfate
3. 3
   여과Filtration and concentration
4. 4
   기타yielded a brown oil which
5. 5
   기타upon purification via normal phase chromatography (0→100% EtOAc in Hx)
6. 6
   기타afforded a brown semi-solid which
7. 7
   기타to yield a dark tan powder
8. 8
   온도the system was heated to 125° C. for 20 minutes in the microwave reactor
9. 9
   기타The reaction contents
10. 10
    기타were partitioned between water and EtOAc
11. 11
    기타followed by purification via normal phase chromatography (20→100% EtOAc in Hx)
12. 12
    기타to yield a clear oil
13. 13
    workup.STIRRINGstirred at 135° C. for 10 minutes in a microwave reactor
14. 14
    기타the solvents were azeotroped off with toluene

실험 절차

To a solution of methyl 2-chloro-5-iodonicotonate (5-1, 10.85 g, 36.5 mmol) in dimethylformamide (150 mL) at 25° C. was added 3-methyl-5-pyridylboronic acid (5.0 g, 36.5 mmol), PdCl2dppf (2.67 g, 3.65 mmol) followed by cesium carbonate (41.6 g, 128 mmol) and water (6.57 mL, 365 mmol) and the system was stirred for 4 h at 25° C. The system was partitioned between water and EtOAc, and dried over magnesium sulfate. Filtration and concentration yielded a brown oil which upon purification via normal phase chromatography (0→100% EtOAc in Hx) afforded a brown semi-solid which was then tritirated with MeOH and diethylether to yield a dark tan powder. To this tan powder (0.5 g, 1.9 mmol) in dioxane (13 mL) was added 3-methylpyrazole (0.47 g, 5.7 mmol) and NaHMDS (1.9 mL, 3.81 mmol) and the system was heated to 125° C. for 20 minutes in the microwave reactor. The reaction contents were partitioned between water and EtOAc followed by purification via normal phase chromatography (20→100% EtOAc in Hx) to yield a clear oil. To this clear oil (0.31 g, 1.0 mmol) in THF (2.5 mL) and MeOH (2.5 mL) was added KOH (2.0 mL, 2.0 mmol) and stirred at 135° C. for 10 minutes in a microwave reactor. The system was then acidified using 6 N HCl to a pH of 2.0 and the solvents were azeotroped off with toluene to afford the title compound (5-2) as a bone powder. ESI+MS [M+H]+ C16H14N4O2=295.1.

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