반응 #169252

반응 방정식

Oxalyl chloride

1-methyl piperidine-4-carboxylic acid

3-amino-5-bromopyridine

→

N-(5-bromopyridin-3-yl)-1-methylpiperidine-4-carboxamide

수율 47.7%

용매

DCM

반응 조건

후처리

1. 1
   기타The volatiles were evaporated under vacuum
2. 2
   workup.ADDITIONPyridine was added to the residue
3. 3
   workup.STIRRINGThe solution was further stirred at room temperature for 3 h under argon
4. 4
   기타The pyridine was evaporated under vacuum
5. 5
   workup.ADDITIONThe residue was treated with water
6. 6
   세척washed with DCM
7. 7
   추출The aqueous layer was extracted with n-butanol
8. 8
   기타The combined organic layer was evaporated
9. 9
   workup.DISSOLUTIONThe residue was dissolved in DCM with the addition of few drops of MeOH
10. 10
    여과The insoluble inorganic solids were filtered off
11. 11
    농축The filtrate was concentrated under vacuum

실험 절차

Oxalyl chloride (8.67 mmol) followed by DMF (2 drops) was added to a solution of 1-methyl piperidine-4-carboxylic acid (XLIII) (5.78 mmol) in DCM and stirred 30 min at room temperature under argon. The volatiles were evaporated under vacuum by avoiding contact with air. Pyridine was added to the residue followed by addition of 3-amino-5-bromopyridine (XL) (5.20 mmol). The solution was further stirred at room temperature for 3 h under argon. The pyridine was evaporated under vacuum. The residue was treated with water, basified by saturated NaHCO3 solution and washed with DCM. The aqueous layer was extracted with n-butanol. The combined organic layer was evaporated. The residue was dissolved in DCM with the addition of few drops of MeOH. The insoluble inorganic solids were filtered off. The filtrate was concentrated under vacuum to get N-(5-bromopyridin-3-yl)-1-methylpiperidine-4-carboxamide (XLIV) as a brown viscous liquid (0.74 g, 43% yield). 1H NMR (DMSO-d6) 1.61-1.69 (m, 2H), 1.77-1.79 (m, 2H), 1.93-1.97 (m, 2H), 2.20 (s, 3H), 2.29-2.35 (m, 1H), 2.84-2.87 (m, 2H), 8.36 (d, J=1.6 Hz, 1H), 8.39 (m, 1H), 8.66 (d, J=1.6 Hz, 1H), 10.33 (s, 1H); ESIMS found C12H16BrN3O m/z 299 (M+H).

출처