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

HRID 62090

反応式

HRID 62090 の反応式
C(Cl)(=O)C(Cl)=O.[CH3:7][N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1.[NH2:17][C:18]1[CH:19]=[N:20][CH:21]=[C:22]([Br:24])[CH:23]=1>CN(C=O)C.C(Cl)Cl>[Br:24][C:22]1[CH:23]=[C:18]([NH:17][C:14]([CH:11]2[CH2:10][CH2:9][N:8]([CH3:7])[CH2:13][CH2:12]2)=[O:16])[CH:19]=[N:20][CH:21]=1

参加物

6

反応物 3

HCID 65578Oxalyl chlorideHCID 8176813-Amino-5-bromopyridineHCID 27369391-Methylpiperidine-4-carboxylic acid

生成物 1

HCID 67341499N-(5-bromopyridin-3-yl)-1-methylpiperidine-4-carboxamide収率 47.7%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒

実験手順

Oxalyl chloride (8.67 mmol) followed by DMF (2drops) 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).

後処理

  1. customThe volatiles were evaporated under vacuum
  2. additionPyridine was added to the residue
  3. stirringThe solution was further stirred at room temperature for 3 h under argon
  4. customThe pyridine was evaporated under vacuum
  5. additionThe residue was treated with water
  6. washwashed with DCM
  7. extractionThe aqueous layer was extracted with n-butanol
  8. customThe combined organic layer was evaporated
  9. dissolutionThe residue was dissolved in DCM with the addition of few drops of MeOH
  10. filtrationThe insoluble inorganic solids were filtered off
  11. concentrationThe filtrate was concentrated under vacuum

出典と根拠

ORDレコード
ord-4e1c9a2a84a3466592378f2189ead22f
出典データセット
uspto-grants-2016_09
特許番号
US09446035B2

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