Potassium Phosphate, Tribasic → 3-(2-fluoro-pyridin-4-yl)-5-nitro-1-trityl-1H-indazole

HRID 1020945Notes

Reaction equation

HRID 1020945 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[CH:9]=2)[N:4]([C:14]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:3]=1.[F:33][C:34]1[CH:39]=[C:38](B(O)O)[CH:37]=[CH:36][N:35]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:33][C:34]1[CH:39]=[C:38]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[CH:9]=3)[N:4]([C:14]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:3]=2)[CH:37]=[CH:36][N:35]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27833962-Fluoropyridine-4-boronic acidHCID 589464433-bromo-5-nitro-1-trityl-1H-indazole

Product 1

HCID 583719213-(2-fluoro-pyridin-4-yl)-5-nitro-1-trityl-1H-indazole

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

3-Bromo-5-nitro-1-trityl-1H-indazole 3BI (15.64 g, 32.3 mmol), 2-fluoro-4-pyridine boronic acid 2BV (5.0 g, 35.5 mmol), K3PO4 (17.1 g, 80.7 mmol) and Pd(dppf)Cl2 (2.64 g, 3.23 mmol) was mixed in dioxane/H2O (240 mL/60 mL) at rt and heated at 80° C. overnight. The reaction mixture was cooled to rt and concentrated to a small volume. The residue was partitioned between ethyl acetate (200 mL) and brine (150 mL). The organic layer was washed with brine, dried (MgSO4) and filtered. The resulting filtrate was concentrated and the residue was purified on silica gel column eluting with hexanes, 5% ethyl acetate in hexanes, 10% ethyl acetate in hexanes sequentially to yield a yellow solid 3BV (3.33 g, 64%).

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. concentrationconcentrated to a small volume
  3. customThe residue was partitioned between ethyl acetate (200 mL) and brine (150 mL)
  4. washThe organic layer was washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationThe resulting filtrate was concentrated
  8. customthe residue was purified on silica gel column
  9. washeluting with hexanes, 5% ethyl acetate in hexanes, 10% ethyl acetate in hexanes sequentially
  10. customto yield a yellow solid 3BV (3.33 g, 64%)

Sources & evidence

ORD record
ord-542fcdd65bef4bacbc658574ac44e3ac
Source dataset
uspto-grants-2014_05
Patent number
US08716483B2

Reaction notes

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