Nicotinic Acid → 3-methyl-N-[3-({2-[(pyridin-3-ylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)phenyl]pyridine-2-carboxamide

HRID 1874541Notes

Reaction equation

HRID 1874541 reaction equation
[NH2:1][C:2]1[N:3]=[C:4]2[CH:9]=[CH:8][C:7]([O:10][C:11]3[CH:12]=[C:13]([NH:17][C:18]([C:20]4[C:25]([CH3:26])=[CH:24][CH:23]=[CH:22][N:21]=4)=[O:19])[CH:14]=[CH:15][CH:16]=3)=[CH:6][N:5]2[CH:27]=1.[N:28]1[CH:33]=[CH:32][CH:31]=[C:30]([C:34](O)=[O:35])[CH:29]=1.Cl.CN(C)CCCN=C=NCC.N1(O)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>C(=O)([O-])O.[Na+].CN(C)C(=O)C>[CH3:26][C:25]1[C:20]([C:18]([NH:17][C:13]2[CH:14]=[CH:15][CH:16]=[C:11]([O:10][C:7]3[CH:8]=[CH:9][C:4]4[N:5]([CH:27]=[C:2]([NH:1][C:34]([C:30]5[CH:29]=[N:28][CH:33]=[CH:32][CH:31]=5)=[O:35])[N:3]=4)[CH:6]=3)[CH:12]=2)=[O:19])=[N:21][CH:22]=[CH:23][CH:24]=1

Participants

8

Reactant 5

HCID 938Nicotinic AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57749390N-{3-[(2-aminoimidazo[1,2-a]pyridin-6-yl)oxy]phenyl}-3-methylpyridine-2-carboxamide

Product 1

HCID 577491353-methyl-N-[3-({2-[(pyridin-3-ylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)phenyl]pyridine-2-carboxamideYield 46%

Reagents, catalysts & solvents 2

HCID 31374DimethylacetamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of N-{3-[(2-aminoimidazo[1,2-a]pyridin-6-yl)oxy]phenyl}-3-methylpyridine-2-carboxamide (150 mg, 0.625 mmol), pyridine-3-carboxylic acid (76.9 mg, 0.625 mmol), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (132 mg, 0.689 mmol), 1H-benzotriazol-1-ol (58.0 mg, 0.429 mmol), N,N-diisopropylethylamine (143 μL, 0.835 mmol) and N,N-dimethylacetamide (5 mL) was stirred at room temperature for 13 hr. The reaction mixture was diluted with aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (NH silica gel, 0%→75% ethyl acetate-hexane) to give the title compound (89.0 mg, 46%) as a pale-yellow solid.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with aqueous sodium hydrogen carbonate solution and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltrated
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (NH silica gel, 0%→75% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-4862d7a2a96540b58c2d4dc0242086a9
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Reaction notes

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