Cesium carbonate → Methyl 6-(6-Chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)nicotinate

HRID 1431154Notes

Reaction equation

HRID 1431154 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1.Br[C:13]1[C:14](=[O:21])[N:15]([CH3:20])[N:16]=[C:17]([Cl:19])[CH:18]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH3:9][O:8][C:6](=[O:7])[C:5]1[CH:10]=[CH:11][C:2]([NH:1][C:13]2[C:14](=[O:21])[N:15]([CH3:20])[N:16]=[C:17]([Cl:19])[CH:18]=2)=[N:3][CH:4]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 737487Methyl 6-aminonicotinateHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

Product 1

HCID 57662841Methyl 6-(6-Chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)nicotinateYield 39.5%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
105 °C

Procedure

Methyl 6-aminonicotinate (2 g, 13.1 mmol, Eq: 1.00), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (2.94 g, 13.1 mmol, Eq: 1), and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis-(diphenylphosphine) (400 mg, 691 μmol, Eq: 0.0526) were dissolved in DMF (300 ml) under heating. Cesium carbonate (12.8 g, 39.4 mmol, Eq: 3) was added followed by Pd2(dba)3 (301 mg, 329 μmol, Eq: 0.025) under an argon atmosphere. The reaction mixture was heated to 105° C. over night. The crude reaction mixture was poured into water (400 ml) and the resulting precipitate was filtered off and washed with water. The resultant filter cake was dissolved in dichloromethane. The organic phase was washed with brine, dried over sodium sulfate; filtered and concentrated to give the desired product as an off-white solid (1.523 g).

Workup

  1. temperatureunder heating
  2. customThe crude reaction mixture
  3. filtrationthe resulting precipitate was filtered off
  4. washwashed with water
  5. filtrationThe resultant filter cake
  6. dissolutionwas dissolved in dichloromethane
  7. washThe organic phase was washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-e4684986ea1747128f8f708305b211d9
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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