Sodium Carbonate → 6-Chloro-4-(4-fluoro-2-methoxy-phenyl)-pyridazin-3-ylamine

HRID 403370

Reaction equation

HRID 403370 reaction equation
Br[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[N:4][C:3]=1[NH2:9].[F:10][C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[C:13]([O:20][CH3:21])[CH:12]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)(O)[O-].[Na+]>COCCOC.C(OCC)(=O)C>[Cl:8][C:6]1[N:5]=[N:4][C:3]([NH2:9])=[C:2]([C:14]2[CH:15]=[CH:16][C:11]([F:10])=[CH:12][C:13]=2[O:20][CH3:21])[CH:7]=1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 2782672(4-Fluoro-2-methoxyphenyl)boronic acidHCID 220244193-Amino-4-bromo-6-chloropyridazine

Product 1

HCID 866984756-Chloro-4-(4-fluoro-2-methoxy-phenyl)-pyridazin-3-ylamine

Reagents, catalysts & solvents 2

HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-bromo-6-chloropyridazin-3-amine (2.5 g, 12.0 mmol, CAS RN 446273-59-2) in 1,2-dimethoxyethane (30 mL) was added 4-fluoro-2-methoxyphenylboronic acid (2.45 g, 14.4 mmol, CAS RN 179899-07-1) and 2M aqueous sodium carbonate solution (10 mL). The reaction mixture was stirred under argon atmosphere for 15 minutes. Pd(II)acetate (135 mg, 600 μmol) and triphenylphosphine (315 mg, 1.2 mmol) was added. The dark red reaction mixture was stirred at 90° C. for 8 hours and then poured on 10% aqueous sodium bicarbonate solution (200 mL) and ethyl acetate (200 mL), filtered over dicalite and the layers were separated. The aqueous layer was extracted a second time with ethyl acetate (200 mL). The organic layers were washed with 200 mL brine, dried over magnesium sulfate, filtered and concentrated under vacuum. The residue was purified by silica gel chromatography on a 120 g column using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 0:100). Light red solid (1.71 g, 56.2%). MS (ESI+): m/z=254.050 ([M+H]+).

Workup

  1. customThe dark red reaction mixture
  2. stirringwas stirred at 90° C. for 8 hours
  3. filtrationfiltered over dicalite
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted a second time with ethyl acetate (200 mL)
  6. washThe organic layers were washed with 200 mL brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customThe residue was purified by silica gel chromatography on a 120 g column
  11. washeluting with a gradient of n-heptane:ethyl acetate (100:0 to 0:100)

Sources & evidence

ORD record
ord-0e1a5ff536574a21ae0f04680c37513e
Source dataset
uspto-grants-2014_06
Patent number
US08748434B2

Linked notes

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