Oxalyl chloride → HCID 57749247, compound

HRID 1874610Notes

Reaction equation

HRID 1874610 reaction equation
[CH3:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([OH:10])=O)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[NH2:17][C:18]1[N:48]=[C:21]2[CH:22]=[CH:23][C:24]([O:26][C:27]3[CH:28]=[C:29]([NH:34][C:35](=[O:47])[C:36]4[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([C:45]#[N:46])([CH3:44])[CH3:43])[CH:37]=4)[CH:30]=[CH:31][C:32]=3[CH3:33])=[CH:25][N:20]2[N:19]=1.C(=O)([O-])O.[Na+]>O1CCCC1.N1C=CC=CC=1.CN(C)C=O>[C:45]([C:42]([C:38]1[CH:37]=[C:36]([C:35]([NH:34][C:29]2[CH:30]=[CH:31][C:32]([CH3:33])=[C:27]([CH:28]=2)[O:26][C:24]2[CH:23]=[CH:22][C:21]3[N:20]([N:19]=[C:18]([NH:17][C:8]([C:5]4[CH:6]=[N:7][C:2]([CH3:1])=[CH:3][CH:4]=4)=[O:10])[N:48]=3)[CH:25]=2)=[O:47])[CH:41]=[CH:40][CH:39]=1)([CH3:44])[CH3:43])#[N:46]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 1378606-Methylnicotinic acidHCID 516892Sodium BicarbonateHCID 68985382N-{3-[(2-amino[1,2,4]triazolo[1,5-a]pyridin-6-yl)oxy]-4-methylphenyl}-3-(1-cyano-1-methylethyl)benzamide

Product 1

HCID 57749247HCID 57749247, compoundYield 49.4%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-methylpyridine-3-carboxylic acid (252 mg, 1.84 mmol) in tetrahydrofuran (6 mL) were added oxalyl chloride (200 μL, 2.30 mmol) and N,N-dimethylformamide (20 μL), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure. The obtained residue and N-{3-[(2-amino[1,2,4]triazolo[1,5-a]pyridin-6-yl)oxy]-4-methylphenyl}-3-(1-cyano-1-methylethyl)benzamide (196 mg, 0.460 mmol) were dissolved in pyridine (7 mL), and the mixture was stirred at room temperature for 7 days. A saturated aqueous sodium hydrogen carbonate solution (20 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (30 mL, 10 mL). The combined organic layer was washed with saturated brine (10 mL) and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/methanol=100/0→99.5/0.5), and fractions containing the desired product were concentrated under reduced pressure. The obtained residue was recrystallized from methanol to give the title compound (124 mg, 49%) as colorless crystals.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. stirringthe mixture was stirred at room temperature for 7 days
  3. extractionthe mixture was extracted with ethyl acetate (30 mL, 10 mL)
  4. washThe combined organic layer was washed with saturated brine (10 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationThe insoluble material was filtered off
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/methanol=100/0→99.5/0.5), and fractions
  9. additioncontaining the desired product
  10. concentrationwere concentrated under reduced pressure
  11. customThe obtained residue was recrystallized from methanol

Sources & evidence

ORD record
ord-45c4e8b7df89460981e8b5addde41bb4
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Reaction notes

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