Nicotinic Acid → HCID 57505758, compound

HRID 1668223Notes

Reaction equation

HRID 1668223 reaction equation
[C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[NH2:16][C:17]1[N:18]=[C:19]2[CH:24]=[CH:23][C:22]([O:25][C:26]3[CH:27]=[C:28]([NH:32][C:33](=[O:45])[C:34]4[CH:39]=[CH:38][CH:37]=[C:36]([C:40]5([C:43]#[N:44])[CH2:42][CH2:41]5)[CH:35]=4)[CH:29]=[CH:30][CH:31]=3)=[N:21][N:20]2[CH:46]=1.C(=O)([O-])O.[Na+]>O1CCCC1.CN(C)C=O.CN1CCCC1=O>[C:43]([C:40]1([C:36]2[CH:35]=[C:34]([CH:39]=[CH:38][CH:37]=2)[C:33]([NH:32][C:28]2[CH:27]=[C:26]([CH:31]=[CH:30][CH:29]=2)[O:25][C:22]2[CH:23]=[CH:24][C:19]3[N:20]([CH:46]=[C:17]([NH:16][C:1](=[O:9])[C:2]4[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=4)[N:18]=3)[N:21]=2)=[O:45])[CH2:41][CH2:42]1)#[N:44]

Participants

8

Reactant 4

HCID 938Nicotinic AcidHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 57505749N-{3-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)oxy]phenyl}-3-(1-cyanocyclopropyl)benzamide

Product 1

HCID 57505758HCID 57505758, compoundYield 53.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of nicotinic acid (54 mg, 0.438 mmol) in tetrahydrofuran (3 mL) were added N,N-dimethylformamide (1 drop) and oxalyl chloride (64 μL, 0.734 mmol), and the mixture was stirred at room temperature for 1 hr. The solvent was evaporated under reduced pressure, and the residue and N-{3-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)oxy]phenyl}-3-(1-cyanocyclopropyl)benzamide (150 mg, 0.365 mmol) were dissolved in N-methylpyrrolidone (3 mL), and the mixture was stirred at room temperature for 14 hr. Saturated aqueous sodium hydrogencarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and filtrated. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=20/80→100/0) to give the title compound (100 mg, 53%) as a pale-green powder.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. stirringthe mixture was stirred at room temperature for 14 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltrated
  7. customThe solvent was evaporated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=20/80→100/0)

Sources & evidence

ORD record
ord-679c4c2415e9447d82d05884b95e9a4f
Source dataset
uspto-grants-2011_10
Patent number
US08044049B2

Reaction notes

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