Potassium Phosphate, Tribasic → 5-[4-(5-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1-(phenylsulfonyl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinamine

HRID 38825Notes

Reaction equation

HRID 38825 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[C:4]([C:20]2[O:21][C:22]([CH2:25][N:26]3[CH2:31][C@H:30]([CH3:32])[O:29][C@H:28]([CH3:33])[CH2:27]3)=[N:23][N:24]=2)[CH:3]=1.[CH3:34][O:35][C:36]1[C:41]([NH2:42])=[CH:40][C:39](B2OC(C)(C)C(C)(C)O2)=[CH:38][N:37]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:33][C@H:28]1[O:29][C@@H:30]([CH3:32])[CH2:31][N:26]([CH2:25][C:22]2[O:21][C:20]([C:4]3[CH:3]=[C:2]([C:39]4[CH:40]=[C:41]([NH2:42])[C:36]([O:35][CH3:34])=[N:37][CH:38]=4)[CH:10]=[C:9]4[C:5]=3[CH:6]=[N:7][N:8]4[S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)(=[O:13])=[O:12])=[N:24][N:23]=2)[CH2:27]1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 595579202-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-amineHCID 666957276-Bromo-4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1-(phenylsulfonyl)-1H-indazole

Product 1

HCID 666916425-[4-(5-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1-(phenylsulfonyl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinamineYield 99.3%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 6-bromo-4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1-(phenylsulfonyl)-1H-indazole (0.82 g, 1.540 mmol) in 1,4-dioxane (15 ml) and water (1.5 ml) was added 2-(methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinamine (0.501 g, 2.002 mmol), 1,1′-bis(diphenylphosphino)ferrocene palladium dichloride (0.225 g, 0.308 mmol) and potassium phosphate tribasic (0.981 g, 4.62 mmol). The mixture was heated at 80° C. for 2 hr, cooled and concentrated in vacuo and the residue partitioned between dichloromethane and water (20 ml), separated by hydrophobic frit and purified by silica (100 g) cartridge on Flashmaster II, using a gradient of dichloromethane and methanol (1% triethylamine) to give the title compound as an orange solid (0.88 g).

Workup

  1. temperaturecooled
  2. concentrationconcentrated in vacuo
  3. customthe residue partitioned between dichloromethane and water (20 ml)
  4. customseparated by hydrophobic frit
  5. custompurified by silica (100 g) cartridge on Flashmaster II

Sources & evidence

ORD record
ord-2e2efd317e354431a7a423e52e7592e3
Source dataset
uspto-grants-2013_09
Patent number
US08524751B2

Reaction notes

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