Isopropanol → (R)-2-(3,4-Difluorophenyl)-4-[3-(tert-butyldimethylsiloxy)-1-butoxy]-5-[4-(methylthio)phenyl]-3(2H)-pyridazinone

HRID 1241870Notes

Reaction equation

HRID 1241870 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:9]2[C:14](=[O:15])[C:13]([O:16][CH2:17][CH2:18][C@H:19]([O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[CH3:20])=[C:12](Br)[CH:11]=[N:10]2)[CH:5]=[CH:6][C:7]=1[F:8].[CH3:30][S:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(O)(C)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[F:1][C:2]1[CH:3]=[C:4]([N:9]2[C:14](=[O:15])[C:13]([O:16][CH2:17][CH2:18][C@H:19]([O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[CH3:20])=[C:12]([C:35]3[CH:36]=[CH:37][C:32]([S:31][CH3:30])=[CH:33][CH:34]=3)[CH:11]=[N:10]2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

7

Reactant 4

HCID 3776IsopropanolHCID 62657Potassium Phosphate, TribasicHCID 27339594-(Methylthio)phenylboronic acidHCID 23598336(R)-2-(3,4-Difluorophenyl)-4-[3-(tert-butyldimethylsiloxy)-1-butoxy]-5-bromo-3(2H)-pyridazinone

Product 1

HCID 68948236(R)-2-(3,4-Difluorophenyl)-4-[3-(tert-butyldimethylsiloxy)-1-butoxy]-5-[4-(methylthio)phenyl]-3(2H)-pyridazinone

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
70 °C

Procedure

Under a nitrogen atmosphere, a mixture of the product from Example 545C (0.98 g, 2 mmol), 4-(methylthio)benzeneboronic acid (0.4 g, 2.4 mmol), K3PO4 (1.2 g, 6 mmol), PdCl2(PPh3)2 (28 mg, 0.04 mmol), isopropanol (9 mL), and water (1 mL) was stirred at 70° C. for 4 hours. The reaction mixture was then cooled to room temperature, water (30 mL) was added and stirring was continued for 2 hours. The crude black precipitate was collected by filtration then washed with water (10 mL) and hexane (10 mL). This title intermediate was used without further purification in the following oxidation/deprotection step.

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. stirringstirring
  3. waitwas continued for 2 hours
  4. filtrationThe crude black precipitate was collected by filtration
  5. washthen washed with water (10 mL) and hexane (10 mL)
  6. customThis title intermediate was used without further purification in the following oxidation/deprotection step

Sources & evidence

ORD record
ord-fb458d7c7c0144a0b527f2ed8b44800b
Source dataset
uspto-grants-2006_10
Patent number
US07115591B2

Reaction notes

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