Sodium Carbonate → 6-(2-fluorophenyl)pyridazin-3-amine

HRID 539775Notes

Reaction equation

HRID 539775 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([NH2:8])=[CH:4][CH:3]=1.[F:9][C:10]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=1.C([O-])([O-])=O.[Na+].[Na+]>CC(O)C.O.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>[F:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[C:2]1[N:7]=[N:6][C:5]([NH2:8])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 216436-Amino-3-chloropyridazineHCID 2856454-Fluorophenylboronic acid

Product 1

HCID 457878336-(2-fluorophenyl)pyridazin-3-amineYield 87.4%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 6-chloropyridazin-3-amine (3.00 g, 23.1 mmol), 4-fluorophenylboronic acid (34.7 mmol), Na2CO3 (69.3 mmol) in 2-propanol (150 mL) and water (50 mL) that has been degassed with N2 (5 minutes) is added PdCl2(PPh3)2(1.15 mmol). The mixture is heated at 80° C. for 12 hours, concentrated under reduced pressure, added sat. aqueous NaHCO3 (100 mL) and extracted with EtOAc (3×100 mL). Organic layer is collected, dried over Na2SO4, filtered and concentrated to dryness. The crude product is purified via chromatography using a gradient of CH2Cl2 to 70% CH2Cl2:EtOAc:methanol (1:1:0.1) to afford the title compound (3.82 g, 87%) as a white solid: Rf 0.37 (1:1:0.1 CH2Cl2:EtOAc:methanol); LCMS (m/z)=190.2 [M+H]+, tR=0.44 min.

Workup

  1. customhas been degassed with N2 (5 minutes)
  2. concentrationconcentrated under reduced pressure
  3. additionadded sat. aqueous NaHCO3 (100 mL)
  4. extractionextracted with EtOAc (3×100 mL)
  5. customOrganic layer is collected
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe crude product is purified via chromatography

Sources & evidence

ORD record
ord-951c318f347d4f728840fcc7772eb6c6
Source dataset
uspto-grants-2014_10
Patent number
US08871767B2

Reaction notes

Loading…