Sodium Carbonate → 8-(2,4-Difluorophenyl)-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyridazine-3-carboxylic acid

HRID 1253630Notes

Reaction equation

HRID 1253630 reaction equation
Cl[C:2]1[C:3]2[N:11]([CH3:12])[C:10](=[O:13])[C:9]([C:14]([O:16]CC)=[O:15])=[CH:8][C:4]=2[CH:5]=[N:6][N:7]=1.O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].[F:31][C:32]1[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=1B(O)O>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:31][C:32]1[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=1[C:2]1[C:3]2[N:11]([CH3:12])[C:10](=[O:13])[C:9]([C:14]([OH:16])=[O:15])=[CH:8][C:4]=2[CH:5]=[N:6][N:7]=1

Participants

7

Reactant 4

HCID 10340Sodium Carbonate2×HCID 312751,4-DioxaneHCID 27343342,4-Difluorophenylboronic acidHCID 46930535Ethyl 8-chloro-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyridazine-3-carboxylate

Product 1

HCID 469305368-(2,4-Difluorophenyl)-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyridazine-3-carboxylic acid

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of ethyl 8-chloro-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyridazine-3-carboxylate (6) (1.40 g, 5.23 mmol) in 3:1 1,4-dioxane: 2 M aq Na2CO3 (16 mL) was added 2,4-difluorophenylboronic acid (1.03 g, 6.54 mmol) and tetrakis(triphenylphosphine)palladium (0) (0.484 g, 0.418 mmol). The reaction mixture was heated in a microwave at 100° C. for 75 min, then more Na2CO3 solid (100 mg) was added and the reaction mixture was heated in the microwave at 100° C. for an additional 2 h. The mixture was diluted with water and washed with CH2Cl2. The aqueous layer was then acidified with 5 N HCl to pH ˜2 and extracted with CHCl3/iPrOH (4:1). The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo to give 8-(2,4-difluorophenyl)-1-methyl-2-oxo-1,2-dihydropyrido[3,2-d]pyridazine-3-carboxylic acid as a brown solid. MS (ESI, pos. ion) m/z: 318 (M+1).

Workup

  1. temperaturethe reaction mixture was heated in the microwave at 100° C. for an additional 2 h
  2. washwashed with CH2Cl2
  3. extractionextracted with CHCl3/iPrOH (4:1)
  4. dry with materialThe combined organic extracts were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-768cc944533d47f4a5898420cdea4e6e
Source dataset
uspto-grants-2013_06
Patent number
US08455495B2

Reaction notes

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