3-Aminopyridine → 5-Iodo-N-(pyridin-3-yl)-6-(2,2,2-trifluoroethoxy)nicotinamide

HRID 469766Notes

Reaction equation

HRID 469766 reaction equation
[I:1][C:2]1[C:3]([O:11][CH2:12][C:13]([F:16])([F:15])[F:14])=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=O.[NH2:17][C:18]1[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C.[OH-].[Na+]>CN(C=O)C>[I:1][C:2]1[C:3]([O:11][CH2:12][C:13]([F:16])([F:15])[F:14])=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([NH:17][C:18]1[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=1)=[O:9]

Participants

7

Reactant 5

HCID 100093-AminopyridineHCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 712944593-Pyridinecarboxylic acid, 5-iodo-6-(2,2,2-trifluoroethoxy)-

Product 1

HCID 712943625-Iodo-N-(pyridin-3-yl)-6-(2,2,2-trifluoroethoxy)nicotinamideYield 64%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Iodo-6-(2,2,2-trifluoroethoxy)nicotinic acid (1 g, 2.88 mmol) was dissolved in DMF (10.0 mL); 3-amino-pyridine (285 mg, 3.03 mmol), TBTU (981 mg, 3.05 mmol) and N,N-diisopropylethylamine (1.8 g, 14.4 mmol) were added and the reaction mixture was stirred for 20 hours. The mixture was poured into 5 mL 1 M NaOH solution and extracted with i-propyl acetate (2×50 mL). The organic layers were combined, dried with Na2SO4 and concentrated in vacuo to give a light yellow solid. Crystallization from dichloromethane afforded the title compound (0.78 g, 64%) as white solid; MS (ESI) 423.9 (M+H)+.

Workup

  1. extractionextracted with i-propyl acetate (2×50 mL)
  2. dry with materialdried with Na2SO4
  3. concentrationconcentrated in vacuo
  4. customto give a light yellow solid
  5. customCrystallization from dichloromethane

Sources & evidence

ORD record
ord-2c2ebcfcc3144917837e6d9c07a8d3f6
Source dataset
uspto-grants-2014_01
Patent number
US08629166B2

Reaction notes

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