2-Chloronicotinic acid → N-benzyl-N-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-2-chloronicotinamide

HRID 1692586Notes

Reaction equation

HRID 1692586 reaction equation
[Cl:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH2:11]([NH:18][CH2:19][CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C1C=CC2N(O)N=NC=2C=1.O.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.O>[CH2:11]([N:18]([CH2:19][CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:23])[CH3:24])[C:4](=[O:6])[C:3]1[CH:7]=[CH:8][CH:9]=[N:10][C:2]=1[Cl:1])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

7

Reactant 4

HCID 762582-Chloronicotinic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 21993563Benzyl({2-[(tert-butyldimethylsilyl)oxy]ethyl})amine

Product 1

HCID 86630355N-benzyl-N-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-2-chloronicotinamideYield 58.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-chloronicotinic acid (7.88 g), N-benzyl-2-{[tert-butyl(dimethyl)silyl]oxy}ethanamine (13.3 g) synthesized by known method (e.g., the method described in WO99/31085) and HOBt-H2O (11.5 g) in DMF (50 mL) was added WSC.HCl (14.4 g), and the mixture was stirred at room temperature for 14 hr. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and brine, and concentrated. The residue was purified by silica gel column chromatography (solvent gradient; 10→33% ethyl acetate/hexane) to give N-benzyl-N-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-2-chloronicotinamide (11.8 g, 58%) as a colorless oil.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and brine
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel column chromatography (solvent gradient; 10→33% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-97d6cec0237442bba06fccf200962011
Source dataset
uspto-grants-2012_04
Patent number
US08158617B2

Reaction notes

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