Water → 1,1-Dimethylethyl 4-[({[6-amino-5-chloro-2-(methyloxy)-3-pyridinyl]carbonyl}amino)methyl]-1-piperidinecarboxylate

HRID 489782Notes

Reaction equation

HRID 489782 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([C:10]([OH:12])=O)=[CH:4][C:3]=1[Cl:13].C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:26][CH2:27][CH:28]1[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]1.O>CN(C)C=O>[NH2:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([C:10]([NH:26][CH2:27][CH:28]2[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]2)=[O:12])=[CH:4][C:3]=1[Cl:13]

Participants

6

Reactant 4

HCID 962WaterHCID 682631,1'-CarbonyldiimidazoleHCID 7368171-Boc-4-(aminomethyl)piperidineHCID 222626616-Amino-5-chloro-2-methoxypyridine-3-carboxylic Acid

Product 1

HCID 222626051,1-Dimethylethyl 4-[({[6-amino-5-chloro-2-(methyloxy)-3-pyridinyl]carbonyl}amino)methyl]-1-piperidinecarboxylateYield 71.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of 6-amino-5-chloro-2-(methyloxy)-3-pyridinecarboxylic acid (Y. Hirokawa et al., Bioorg. Med. Chem. Lett., 1998, 12, 1551–1554, 500 mg, 2.47 mmol) and 1,1′-carbonyldiimidazole (440 mg, 2.71 mmol) in N,N-dimethylformamide (15 ml) was stirred at room temperature for 45 min. A solution of 1,1-dimethylethyl 4-(aminomethyl)-1-piperidinecarboxylate (529 mg, 2.47 mmol) in N,N-dimethylformamide (5 ml) was added and the resulting mixture was stirred at room temperature for 5 h. The mixture was poured into water (200 ml) and extracted with ethyl acetate/toluene (2:1, 200 ml×3). The combined organic layer was washed with water, dried over magnesium sulfate, and concentrated in vacuo. The obtained residue was chromatographed on a column of silica gel eluting with methanol/dichloromethane (1:25) to give 703 mg (71%) of the title compound as a pale yellow amorphous solid.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 5 h
  2. extractionextracted with ethyl acetate/toluene (2:1, 200 ml×3)
  3. washThe combined organic layer was washed with water
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe obtained residue was chromatographed on a column of silica gel eluting with methanol/dichloromethane (1:25)

Sources & evidence

ORD record
ord-18e57dc0cf3f40ea83c8a23523393e43
Source dataset
uspto-grants-2005_12
Patent number
US06979690B2

Reaction notes

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