Potassium Phosphate, Tribasic → 2-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamide

HRID 62502Notes

Reaction equation

HRID 62502 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](I)[C:5]([Cl:9])=[CH:4][N:3]=1.[NH2:10][C:11]1[CH:21]=[CH:20][CH:19]=[CH:18][C:12]=1[C:13]([NH:15][O:16][CH3:17])=[O:14].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C(OC3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=CC=3)=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([NH:10][C:11]2[CH:21]=[CH:20][CH:19]=[CH:18][C:12]=2[C:13]([NH:15][O:16][CH3:17])=[O:14])[C:5]([Cl:9])=[CH:4][N:3]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 123927072-Amino-N-methoxybenzamideHCID 534009652,5-Dichloro-4-iodopyridine

Product 1

HCID 575168962-[(2,5-dichloro-4-pyridinyl)amino]-N-(methyloxy)benzamideYield 87.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 4285986Bis[2-(diphenylphosphino)phenyl] etherCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 2,5-dichloro-4-iodo-pyridine (40 g, 146.5 mmole, 1 eq), 2-amino-N-methoxy-benzamide (24.32 g, 146.5 mmole, 1 eq) and K3PO4 (77.72 g 366.2 mmole, 2.5 eq) in 1,4-dioxane (600 mL) was degassed with N2 for 1 h. To this were added Pd(OAc)2 (0.657 g, 2.93 mmole, 0.02 eq), DPEPhos (6.31 g, 11.7 mmole, 0.08 eq) and again degassed for 15 min with N2. The resulting mixture was stirred at 110° C. for overnight. After completion of reaction, solid material was collected by filtration, dissolved in water (500 mL) and extracted with ethyl acetate (5×200 mL). Combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. Solid compound so obtained was purified by washing with hexane to give the title compound as yellowish solid (40 g, 53%). 1H-NMR (400 MHz, DMSO-d6): δ 3.63 (s, 3H), 7.06 (s, 1H), 7.15-7.22 (m, 1H), 7.48-7.57 (m, 2H), 7.66-7.67 (d, 1H, J=7.48 Hz), 8.25 (s, 1H), 10.66-11.45 (brs, 1H). LC-MS [M+H]+=312.3.

Workup

  1. customwas degassed with N2 for 1 h
  2. customagain degassed for 15 min with N2
  3. customAfter completion of reaction, solid material
  4. filtrationwas collected by filtration
  5. dissolutiondissolved in water (500 mL)
  6. extractionextracted with ethyl acetate (5×200 mL)
  7. dry with materialCombined organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customSolid compound so obtained
  11. customwas purified
  12. washby washing with hexane

Sources & evidence

ORD record
ord-c9e09b0554cb4812a5d43ba4fb268a88
Source dataset
uspto-grants-2016_09
Patent number
US09446034B2

Reaction notes

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