Pyridine → HCID 68532605, compound

HRID 644245Notes

Reaction equation

HRID 644245 reaction equation
[CH3:1][O:2][CH2:3][O:4][C:5]1[CH:13]=[C:12]([C:14]2([CH3:19])[O:18][CH2:17][CH2:16][O:15]2)[CH:11]=[CH:10][C:6]=1[C:7]([O-:9])=O.[Li+].C(Cl)(=O)C(Cl)=O.N1C=CC=CC=1.[Cl:33][C:34]1[CH:35]=[CH:36][C:37]([NH:40][C:41](=[O:49])[C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=2[NH2:48])=[N:38][CH:39]=1>C(Cl)Cl.CN(C=O)C>[Cl:33][C:34]1[CH:35]=[CH:36][C:37]([NH:40][C:41](=[O:49])[C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=2[NH:48][C:7](=[O:9])[C:6]2[CH:10]=[CH:11][C:12]([C:14]3([CH3:19])[O:18][CH2:17][CH2:16][O:15]3)=[CH:13][C:5]=2[O:4][CH2:3][O:2][CH3:1])=[N:38][CH:39]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 219063812-amino-N-(5-chloropyridin-2-yl)benzamideHCID 68532657HCID 68532657, compound

Product 1

HCID 68532605HCID 68532605, compoundYield 76.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a suspension of lithium 2-(methoxymethoxy)-4-(2-methyl-1,3-dioxolan-2-yl)-benzoate (0.08 g, 0.29 mmol) in CH2Cl2 (2 mL) at 0° C. was added DMF (2 drops) followed by oxalyl chloride (0.025 mL, 0.29 mmol). Vigorous bubbling occurred. The reaction was stirred at room temperature for 30 min and then the solvent was removed under reduced pressure. The residue was suspended in CH2Cl2 (10 mL) and cooled to 0° C. Pyridine (0.07 mL, 0.87 mmol) and N-(5-chloropyridiri-2-yl)-2-aminobenzamide (0.072 g, 0.29 mmol) were added and the reaction was stirred at room temperature for 6 h. The reaction was quenched with H2O:EtOAc (10 mL each) and extracted with EtOAc (3×30 mL). The organic solution was washed with 2 NHC (cold), H2O (10 mL), 2 N NaOH (cold) and H2O (10 mL), dried (Na2 SO4), and concentrated. The resulting residue was purified by silica gel flash chromatography (n-hexanes through 30% EtOAc/n-hexanes) to obtain the desired product (0.110 g, 76%); TLC Rf: 0.42 (40% EtOAc/n-hexanes).

Workup

  1. customVigorous bubbling
  2. customthe solvent was removed under reduced pressure
  3. temperaturecooled to 0° C
  4. stirringthe reaction was stirred at room temperature for 6 h
  5. customThe reaction was quenched with H2O
  6. extractionEtOAc (10 mL each) and extracted with EtOAc (3×30 mL)
  7. washThe organic solution was washed with 2 NHC (cold), H2O (10 mL), 2 N NaOH (cold) and H2O (10 mL)
  8. customdried (Na2 SO4)
  9. concentrationconcentrated
  10. customThe resulting residue was purified by silica gel flash chromatography (n-hexanes through 30% EtOAc/n-hexanes)

Sources & evidence

ORD record
ord-d12a8341f6d44050b75e3e0458e25f10
Source dataset
uspto-grants-2010_04
Patent number
US07700628B2

Reaction notes

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