Nitrogen → HCID 67467226, compound

HRID 1476483Notes

Reaction equation

HRID 1476483 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=2[CH3:24])=[O:15])[C:5]2[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.[C:27]1(B(O)O)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].N#N>CO.C(Cl)(Cl)Cl.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].C(Cl)Cl.ClCCl.CCOC(C)=O.O.O1CCOCC1>[NH3:7].[CH3:24][C:23]1[CH:22]=[C:21]([CH3:25])[NH:20][C:19](=[O:26])[C:18]=1[CH2:17][NH:16][C:14]([C:4]1[C:5]2[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=[C:2]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:3]=1)=[O:15]

Participants

13

Reactant 4

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 66827Phenylboronic AcidHCID 545964906-bromo-N-((1,2-dihydro-4,6-dimethyl-2-oxopyridin-3-yl)methyl)-1-isopropyl-1H-indazole-4-carboxamide

Product 2

HCID 222AmmoniaHCID 67467226HCID 67467226, compoundYield 138.2%

Reagents, catalysts & solvents 7

HCID 178418807HCID 178418807, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 6-bromo-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-indazole-4-carboxamide (0.15 g, 0.359 mmol), phenylboronic acid (0.088 g, 0.719 mmol) and potassium phosphate (tribasic) (0.229 g, 1.078 mmol) was added 1,4-dioxane (3 mL) and water (0.75 mL). The suspension was degassed with N2 for 10 min, at which time PdCl2(dppf)-CH2Cl2 (0.044 g, 0.054 mmol) was added and the sealed reaction heated at 100° C. overnight. Diluted reaction with EtOAc and filtered through Celite, washing with EtOAc and concentrating in vacuo to a residue that was dissolve in a minimum amount of DCM. Purification by silica gel chromatography (12 gram Isco GOLD silica column; Gradient B: 5-80%; A: dichloromethane, B: 10% (2 M ammonia in methanol) in chloroform) gave N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-6-phenyl-1H-indazole-4-carboxamide (0.105 g, 0.248 mmol, 69.1% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.50 (d, J=6.57 Hz, 6H) 2.12 (s, 3H) 2.22 (s, 3H) 4.39 (d, J=4.80 Hz, 2H) 5.10-5.24 (m, 1H) 5.89 (s, 1H) 7.37-7.46 (m, 1H) 7.48-7.55 (m, 2H) 7.82-7.93 (m, 3H) 8.12 (s, 1H) 8.38 (s, 1H) 8.66 (t, J=4.93 Hz, 1H) 11.54 (s, 1H). MS (ES) [M+H]+ 415.1.

Workup

  1. additionwas added
  2. customthe sealed reaction
  3. additionDiluted
  4. filtrationfiltered through Celite
  5. washwashing with EtOAc
  6. concentrationconcentrating in vacuo to a residue that
  7. dissolutionwas dissolve in a minimum amount of DCM
  8. customPurification by silica gel chromatography (12 gram Isco GOLD silica column

Sources & evidence

ORD record
ord-048a48b5f38e452bb235e7043ba37019
Source dataset
uspto-grants-2015_04
Patent number
US09018382B2

Reaction notes

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