Cesium carbonate → 3-[(2-Fluoro-4-iodophenyl)amino]-5-[(4-methylpent-3-en-1-yl)oxy]isonicotinamide

HRID 2167224Notes

Reaction equation

HRID 2167224 reaction equation
F[C:2]1[CH:10]=[N:9][CH:8]=[C:7]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=2[F:19])[C:3]=1[C:4]([NH2:6])=[O:5].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:26][C:27]([CH3:32])=[CH:28][CH2:29][CH2:30][OH:31]>CN(C=O)C>[F:19][C:13]1[CH:14]=[C:15]([I:18])[CH:16]=[CH:17][C:12]=1[NH:11][C:7]1[CH:8]=[N:9][CH:10]=[C:2]([O:31][CH2:30][CH2:29][CH:28]=[C:27]([CH3:32])[CH3:26])[C:3]=1[C:4]([NH2:6])=[O:5]

Participants

5

Reactant 3

HCID 10796Cesium carbonate2×HCID 1365824-Methylpent-3-en-1-ol2×HCID 675154073-Fluoro-5-[(2-fluoro-4-iodophenyl)amino]isonicotinamide

Product 1

HCID 569706863-[(2-Fluoro-4-iodophenyl)amino]-5-[(4-methylpent-3-en-1-yl)oxy]isonicotinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

500 mg of 3-fluoro-5-[(2-fluoro-4-iodophenyl)amino]isonicotinamide (0.253 mmol, 1. eq.) were dissolved in 5 ml of DMF, then 1225 mg of cesium carbonate (3.759 mmol, 3 eq.) and 125 mg of 4-methyl-3-pentene-1-ol (0.253 mmol, 1 eq.) were added. The resulting mixture was stirred at 70° C. bath temperature for 24 hours. Since the reaction was not complete, the mixture was stirred for another 2 days at 70° C. bath temperature. Since the reaction was not complete, another 125 mg of 4-methyl-3-pentene-1-ol (0.253 mmol, 1 eq.) and 408 mg of cesium carbonate (0.253 mmol, 1 eq.) were added, and the mixture was stirred for another 2 days at 70° C. bath temperature. The resulting mixture was partitioned between aq. NH4Cl solution (50 ml) and dichloromethane (50 ml). The phases were separated and the aqueouse layer was reextracted twice with dichloromethane (50 ml each). The combined organic layers were washed with brine (50 ml), dried over a silicone filter and concentrated in vacuo. The residue was suspended in ethyl acetate and stirred for 1 h, after which the precipitate was filtered off and dried in vacuo to yield 252 mg (0.52 mmol, 42%) of the analytically pure target compound.

Workup

  1. stirringthe mixture was stirred for another 2 days at 70° C. bath temperature
  2. stirringthe mixture was stirred for another 2 days at 70° C. bath temperature
  3. customThe resulting mixture was partitioned between aq. NH4Cl solution (50 ml) and dichloromethane (50 ml)
  4. customThe phases were separated
  5. washThe combined organic layers were washed with brine (50 ml)
  6. dry with materialdried over a silicone
  7. filtrationfilter
  8. concentrationconcentrated in vacuo
  9. stirringstirred for 1 h
  10. filtrationafter which the precipitate was filtered off
  11. customdried in vacuo
  12. customto yield 252 mg (0.52 mmol, 42%) of the analytically pure target compound

Sources & evidence

ORD record
ord-f156753443a142d0a41e17fd55ca4331
Source dataset
uspto-grants-2015_06
Patent number
US09045429B2

Reaction notes

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