Cesium carbonate → 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide

HRID 1045913Notes

Reaction equation

HRID 1045913 reaction equation
[NH2:1][C:2]1[CH:12]=[CH:11][CH:10]=[CH:9][C:3]=1[C:4]([NH:6][O:7][CH3:8])=[O:5].[Cl:13][C:14]1[CH:19]=[C:18](I)[C:17]([Cl:21])=[CH:16][N:15]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:13][C:14]1[CH:19]=[C:18]([NH:1][C:2]2[CH:12]=[CH:11][CH:10]=[CH:9][C:3]=2[C:4]([NH:6][O:7][CH3:8])=[O:5])[C:17]([Cl:21])=[CH:16][N:15]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 123927072-Amino-N-methoxybenzamideHCID 534009652,5-Dichloro-4-iodopyridine

Product 1

HCID 575168962-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamideYield 33.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Palladium acetate (0.071 g, 0.32 mmol) was added under a nitrogen atmosphere to 2-amino-N-methoxybenzamide (1.32 g, 7.94 mmol) in dioxane (80 mL) containing 2,5-dichloro-4-iodopyridine (2.176 g, 7.94 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.276 g, 0.48 mmol) and cesium carbonate (5.18 g, 15.89 mmol). The resulting suspension was heated at 80° C. for 18 hours and then at 85° C. for a further 24 hours. The mixture was filtered through Celite and then concentrated in vacuo. The residue was diluted with MeOH and then loaded onto an SCX column. The mixture was eluted first with MeOH and then with a 7N solution of NH3 in MeOH. Fractions containing product were combined and then evaporated. The residue was triturated with Et2O to leave 2-[(2,5-dichloropyridin-4-yl)amino]-N-methoxybenzamide (0.823 g, 33% yield); 1H NMR spectrum: (300 MHz, DMSO) δ 3.66 (3H, s), 7.02 (1H, s), 7.26 (1H, m), 7.38 (1H, m), 7.56-7.64 (2H, m), 8.27 (1H, s), 9.66 (1H, s), 11.88 (1H, s); Mass spectrum: m/z (ESI+) (M+H)+=311.93 and 313.96 and 315.92.

Workup

  1. filtrationThe mixture was filtered through Celite
  2. concentrationconcentrated in vacuo
  3. additionThe residue was diluted with MeOH
  4. washThe mixture was eluted first with MeOH
  5. additionFractions containing product
  6. customevaporated
  7. customThe residue was triturated with Et2O

Sources & evidence

ORD record
ord-7a2fb01ede314fedbf35fd7b622cb2f8
Source dataset
uspto-grants-2013_10
Patent number
US08569298B2

Reaction notes

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