1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 5-amino-N-(3-(tert-butyldimethylsilyloxy)propyl)-2-chloroisonicotinamide

HRID 60160Notes

Reaction equation

HRID 60160 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][C:5]([Cl:11])=[N:4][CH:3]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Si:33]([O:40][CH2:41][CH2:42][CH2:43][NH2:44])([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34]>CN(C=O)C.CC(=O)OCC.O>[NH2:1][C:2]1[C:7]([C:8]([NH:44][CH2:43][CH2:42][CH2:41][O:40][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])=[O:10])=[CH:6][C:5]([Cl:11])=[N:4][CH:3]=1

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 11074190(3-Aminopropoxy)(tert-butyl)dimethylsilaneHCID 227367915-Amino-2-chloro-isonicotinic acid

Product 1

HCID 1317370795-amino-N-(3-(tert-butyldimethylsilyloxy)propyl)-2-chloroisonicotinamideYield 43.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-amino-2-chloroisonicotinic acid (5 g, 0.029 mol) in DMF (40 mL) was added EDCI (8.34 g, 0.0435 mol) and HOBT (5.87 g, 0.0435 mol). The reaction was stirred at RT for 30 min then 3-(tert-butyldimethylsilyloxy)propan-1-amine (5.5 g, 0.029 mol) was added. The reaction was stirred at RT for 5 h then poured in EA (50 mL) and water (20 mL). The organic layer was washed with brine (50 mL), dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (2:1) to give 5-amino-N-(3-(tert-butyldimethylsilyloxy)propyl)-2-chloroisonicotinamide (4.3 g, 43% yield) as a white solid. LCMS: MH+ 344 and TR=1.877 min.

Workup

  1. stirringThe reaction was stirred at RT for 5 h
  2. washThe organic layer was washed with brine (50 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to a residue which
  5. customwas purified by chromatography
  6. washeluted with PE/EA (2:1)

Sources & evidence

ORD record
ord-794b798882284710a7860b0bd603612c
Source dataset
uspto-grants-2016_09
Patent number
US09440973B2

Reaction notes

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