HCID 89782899, compound → HCID 89782954, compound

HRID 58114Notes

Reaction equation

HRID 58114 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[C:15]2[C:10](=[C:11](B3OC(C)(C)C(C)(C)O3)[CH:12]=[C:13]([C:16]([F:19])([F:18])[F:17])[CH:14]=2)[CH:9]=[N:8]1.Br[C:30]1[C:31]([CH3:47])=[N:32][N:33]([CH2:40][C:41]2[CH:42]=[N:43][N:44]([CH3:46])[CH:45]=2)[C:34]=1[C:35]([O:37][CH2:38][CH3:39])=[O:36]>O1CCOCC1.C([O-])(O)=O.[Na+].CCOC(C)=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]>[CH3:47][C:31]1[C:30]([C:11]2[CH:12]=[C:13]([C:16]([F:17])([F:19])[F:18])[CH:14]=[C:15]3[C:10]=2[CH:9]=[N:8][N:7]3[CH:2]2[CH2:3][CH2:4][CH2:5][CH2:6][O:1]2)=[C:34]([C:35]([O:37][CH2:38][CH3:39])=[O:36])[N:33]([CH2:40][C:41]2[CH:42]=[N:43][N:44]([CH3:46])[CH:45]=2)[N:32]=1

Participants

7

Reactant 2

HCID 89782899HCID 89782899, compoundHCID 89783710HCID 89783710, compound

Product 1

HCID 89782954HCID 89782954, compound

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
140 °C

Procedure

To a microwave vial were added 1-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)-1H-indazole (0.993 g, 2.506 mmol), ethyl 4-bromo-3-methyl-1-((1-methyl-1H-pyrazol-4-yl)methyl)-1H-pyrazole-5-carboxylate (0.82 g, 2.506 mmol), and PdCl2(dppf) (0.092 g, 0.125 mmol) in dioxane (25 mL) and aqueous saturated NaHCO3 (6 mL). The mixture was bubbled with nitrogen to give a light yellow suspension, which was heated at 140° C. for 60 minutes in a microwave reactor. The reaction mixture was subsequently diluted with EtOAc, washed with water and brine, dried over Na2SO4, and concentrated. The crude residue was purified by CombiFlash® chromatography (120 g column) eluting with a gradient of 10-100% EtOAc in heptane over a period of 180 minutes. The product-containing fractions were combined and concentrated to give the title compound as an off white solid (0.745 g, 57.5%). ESI-MS m/z [M+H]+ calc'd for C25H27F3N6O3, 517.22. found 517.20.

Workup

  1. customThe mixture was bubbled with nitrogen
  2. customto give a light yellow suspension, which
  3. washwashed with water and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude residue was purified by CombiFlash® chromatography (120 g column)
  7. washeluting with a gradient of 10-100% EtOAc in heptane over a period of 180 minutes
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-bae612ba1a77448198f32446077568d8
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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