Sodium Methoxide → 3-[(2-Fluoro-4-iodophenyl)amino]-5-methoxyisonicotinamide

HRID 2167226Notes

Reaction equation

HRID 2167226 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].[CH3:20][O-:21].[Na+]>O1CCCC1>[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:21][CH3:20])[C:3]=1[C:4]([NH2:6])=[O:5]

Participants

4

Reactant 2

HCID 10942334Sodium Methoxide2×HCID 675154073-Fluoro-5-[(2-fluoro-4-iodophenyl)amino]isonicotinamide

Product 1

HCID 569709203-[(2-Fluoro-4-iodophenyl)amino]-5-methoxyisonicotinamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

140 mg of 3-fluoro-5-[(2-fluoro-4-iodophenyl)amino]isonicotinamide (0.340 mmol, 1 eq.) were dissolved in 3 mL of tetrahydrofurane and cooled to −75° C. bath temperature upon which 18 mg sodium methoxide (0.340 mmol, 1 eq.) were added and the mixture allowed to come to room temperature. Then the mixture was stirred at 80° C. bath temperature for 3 days. Since the reaction was not completed another 18 mg sodium methoxide (0.340 mmol, 1 eq.) were added and the mixture stirred at 80° C. bath temperature for 1 more day. The reaction mixture was concentrated in vacuo and the residue was partitioned between 20 ml each of water and dichloromethane. The aqueouse layer was separated and reextracted twice with dichloromethane (20 ml each). The combined organic layers were washed with brine (30 ml), dried over a silicone filter and concentrated. The residue was purified by flash chromatography to afford 67 mg (0.17 mmol, 51%) of the analytically pure target compound.

Workup

  1. additionwere added
  2. customto come to room temperature
  3. additionwere added
  4. stirringthe mixture stirred at 80° C. bath temperature for 1 more day
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. customthe residue was partitioned between 20 ml each of water and dichloromethane
  7. customThe aqueouse layer was separated
  8. washThe combined organic layers were washed with brine (30 ml)
  9. dry with materialdried over a silicone
  10. filtrationfilter
  11. concentrationconcentrated
  12. customThe residue was purified by flash chromatography
  13. customto afford 67 mg (0.17 mmol, 51%) of the analytically pure target compound

Sources & evidence

ORD record
ord-71e068e6058c4920926f2895a76eac12
Source dataset
uspto-grants-2015_06
Patent number
US09045429B2

Reaction notes

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