Ammonia → (2S)-2-{2-[4-(3-pyridyl)phthalazin-1(2H)-on-2-yl]isonicotinoylamino}-3-(3,4-dimethoxyphenyl)-1-propanol

HRID 1739433Notes

Reaction equation

HRID 1739433 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][N:24]=1)[C:5]([NH:7][C@@H:8]([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=1)[CH2:9][OH:10])=[O:6].C(=O)([O-])[O-].[K+].[K+].[N:31]1[CH:36]=[CH:35][CH:34]=[C:33]([C:37]2[C:46]3[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=3)[C:40](=[O:47])[NH:39][N:38]=2)[CH:32]=1.N>CN(C)C=O.[Cu]I>[N:31]1[CH:36]=[CH:35][CH:34]=[C:33]([C:37]2[C:46]3[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=3)[C:40](=[O:47])[N:39]([C:2]3[CH:3]=[C:4]([CH:22]=[CH:23][N:24]=3)[C:5]([NH:7][C@@H:8]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=3)[CH2:9][OH:10])=[O:6])[N:38]=2)[CH:32]=1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 11430Potassium CarbonateHCID 100138394-(3-pyridyl)phthalazin-1(2H)-oneHCID 57095136(2S)-2-(2-bromoisonicotinoylamino)-3-(3,4-dimethoxyphenyl)-1-propanol

Product 1

HCID 18393034(2S)-2-{2-[4-(3-pyridyl)phthalazin-1(2H)-on-2-yl]isonicotinoylamino}-3-(3,4-dimethoxyphenyl)-1-propanolYield 20.2%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of (2S)-2-(2-bromoisonicotinoylamino)-3-(3,4-dimethoxyphenyl)-1-propanol (1.2 g) in dimethylformamide (40 ml) are added potassium carbonate (0.88 g) and copper (I) iodide (0.61 g) at room temperature under nitrogen atmosphere. The mixture is heated with stirring at 120° C. for 30 minutes. To the reaction mixture is added 4-(3-pyridyl)phthalazin-1(2H)-one (1.42 g), and the mixture is heated with stirring at 130° C. for two hours. The reaction mixture is cooled to room temperature, and thereto is added aqueous ammonia. The mixture is extracted with chloroform, and the extract is washed, dried and concentrated. The residue is purified by silica gel chromatography (solvent; chloroform:acetone=1:1) to give (2S)-2-{2-[4-(3-pyridyl)phthalazin-1(2H)-on-2-yl]isonicotinoylamino}-3-(3,4-dimethoxyphenyl)-1-propanol (330 mg).

Workup

  1. temperatureThe mixture is heated
  2. temperaturethe mixture is heated
  3. stirringwith stirring at 130° C. for two hours
  4. temperatureThe reaction mixture is cooled to room temperature
  5. extractionThe mixture is extracted with chloroform
  6. washthe extract is washed
  7. customdried
  8. concentrationconcentrated
  9. customThe residue is purified by silica gel chromatography (solvent; chloroform:acetone=1:1)

Sources & evidence

ORD record
ord-803573f5a19c4a8b9c667cbdf9d553b1
Source dataset
uspto-grants-1999_10
Patent number
US05965730

Reaction notes

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