Dimethylformamide → 1-(2-Fluoro-5-iodophenyl)-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide

HRID 1407173Notes

Reaction equation

HRID 1407173 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([I:8])=[CH:4][C:3]=1[N:9]1[CH:14]=[C:13]([O:15][CH3:16])[C:12](=[O:17])[C:11]([C:18]([OH:20])=O)=[N:10]1.C1N=CN(C([N:28]2[CH:32]=NC=C2)=O)C=1.CN([CH:36]=[O:37])C.CCN(C(C)C)C(C)C>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([I:8])=[CH:4][C:3]=1[N:9]1[CH:14]=[C:13]([O:15][CH3:16])[C:12](=[O:17])[C:11]([C:18]([N:28]([O:37][CH3:36])[CH3:32])=[O:20])=[N:10]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 594362491-(2-Fluoro-5-iodophenyl)-5-methoxy-4-oxo-1,4-dihydropyridazine-3-carboxylic acid

Product 1

HCID 594362381-(2-Fluoro-5-iodophenyl)-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamideYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 1-(2-fluoro-5-iodophenyl)-5-methoxy-4-oxo-1,4-dihydropyridazine-3-carboxylic acid (9.96 g, 25.5 mmol) and CDI (4.55 g, 28.1 mmol) in THF (200 mL) was heated to 40° C. for 30 min and 50° C. for 90 min. To the mixture was added DMF (20 mL). The mixture was stirred at 50° C. for 70 min. To the solution were added N,0-dimethylhydroxylamine hydrochloride (3.74 g, 38.3 mmol) and i-Pr2NEt (6.67 mL, 38.3 mmol) at room temperature. The solution was stirred at room temperature for 16 h. The mixture was concentrated in vacuo, diluted with water and 1 M HCl aqueous solution, extracted with EtOAc, washed with saturated NaHCO3 aqueous solution, dried over Na2SO4, filtered, concentrated in vacuo and purified by column chromatography on silica gel (hexane/EtOAc=20/80 to 0/100 and EtOAc/MeOH=100/0 to 0/100) and triturated with MeOH/EtOH/hexane to yield the title compound (9.11 g, 82% yield) as a pale yellow solid: 1H NMR (DMSO-d6, 300 MHz): δ ppm 3.24 (3H, s), 3.56 (3H, s), 3.80 (3H, s), 7.36 (1H, dd, J=10.6, 8.7 Hz), 7.93 (1H, ddd, J=8.7, 4.5, 2.3 Hz), 8.12 (1H, dd, J=7.4, 2.1 Hz), 8.53 (1H, s).

Workup

  1. stirringThe solution was stirred at room temperature for 16 h
  2. concentrationThe mixture was concentrated in vacuo
  3. additiondiluted with water and 1 M HCl aqueous solution
  4. extractionextracted with EtOAc
  5. washwashed with saturated NaHCO3 aqueous solution
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. custompurified by column chromatography on silica gel (hexane/EtOAc=20/80 to 0/100 and EtOAc/MeOH=100/0 to 0/100)
  10. customtriturated with MeOH/EtOH/hexane

Sources & evidence

ORD record
ord-e531f694216545fc968e0e071cfef52b
Source dataset
uspto-grants-2014_12
Patent number
US08916566B2

Reaction notes

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