Potassium Phosphate, Tribasic → HCID 22609906, compound

HRID 2306611Notes

Reaction equation

HRID 2306611 reaction equation
Br[C:2]1[C:7]([O:8][CH2:9][C:10]2[N:11]([CH3:15])[N:12]=[CH:13][N:14]=2)=[N:6][N:5]2[C:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[F:25])=[N:17][N:18]=[C:4]2[CH:3]=1.[F:26][C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:26][C:27]1[CH:32]=[C:31]([C:2]2[C:7]([O:8][CH2:9][C:10]3[N:11]([CH3:15])[N:12]=[CH:13][N:14]=3)=[N:6][N:5]3[C:16]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[F:25])=[N:17][N:18]=[C:4]3[CH:3]=2)[CH:30]=[CH:29][CH:28]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27339863-Fluorophenylboronic acidHCID 154861777-bromo-3-(2-fluorophenyl)-6-(2-methyl2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo[4,3-b]pyridazine

Product 1

HCID 22609906HCID 22609906, compoundYield 35%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A stirred mixture of 7-bromo-3-(2-fluorophenyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-1,2,4-triazolo [4,3-b]pyridazine (50.2 mg, 0.124 mmol), 3-fluorobenzeneboronic acid (24.7 mg, 0.177 mmol), potassium phosphate (74.1 mg, 0.339 mmol), and tetrakis(triphenylphosphine)-palladium(0) (11.5 mg, 0.00995 mmol) in anhydrous DMF (3 ml) was degassed by evaporating and refilling the flask with nitrogen four times, then heated at 100° C. under nitrogen for 14.5 h. The mixture was partitioned between ethyl acetate (20 ml) and brine (15 ml). The aqueous layer was further extracted with ethyl acetate (2×20 ml) and the combined organic extracts were evaporated in vacuo. The residue was purified by flash chromatography (silica gel, 2% MeOH/CH2Cl2) to afford 18.1 mg (35%) of the title compound as a white solid: m.p. 204-206° C. (CH2Cl2-EtOAc-hexane); 1H NMR (360 MHz, CDCl3) δ 3.70 (3H, s), 5.54 (2H, s), 7.18 (1H, m), 7.28-7.40 (4H, m), 7.46 (1H, m), 7.58 (1H, m), 7.86 (1H, s), 7.88 (1H, td, J=7.5 and 1.8 Hz), 8.08 (1H, s); MS (ES+) m/e 420 [MH]+.

Workup

  1. customwas degassed
  2. customby evaporating
  3. customThe mixture was partitioned between ethyl acetate (20 ml) and brine (15 ml)
  4. extractionThe aqueous layer was further extracted with ethyl acetate (2×20 ml)
  5. customthe combined organic extracts were evaporated in vacuo
  6. customThe residue was purified by flash chromatography (silica gel, 2% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-44f5a821a84b46b8893a8f2d634eb006
Source dataset
uspto-grants-2004_12
Patent number
US06828322B2

Reaction notes

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