[1-(4-cyanophenyl)-1H-pyrazol-5-yl]boronic acid → 5-[1-(4-Cyanophenyl)-1H-pyrazol-5-yl]-N,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide

HRID 1672595Notes

Reaction equation

HRID 1672595 reaction equation
I[C:2]1[CH:3]=[C:4]([C:20]([NH:22][CH3:23])=[O:21])[C:5](=[O:19])[N:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[C:7]=1[CH3:8].[C:24]([C:26]1[CH:31]=[CH:30][C:29]([N:32]2[C:36](B(O)O)=[CH:35][CH:34]=[N:33]2)=[CH:28][CH:27]=1)#[N:25]>COCCOC.C([O-])([O-])=O.[Na+].[Na+].C(OCC)(=O)C.[Pd].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[C:24]([C:26]1[CH:27]=[CH:28][C:29]([N:32]2[C:36]([C:2]3[CH:3]=[C:4]([C:20]([NH:22][CH3:23])=[O:21])[C:5](=[O:19])[N:6]([C:9]4[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=4)[C:7]=3[CH3:8])=[CH:35][CH:34]=[N:33]2)=[CH:30][CH:31]=1)#[N:25]

Participants

7

Reactant 2

HCID 66738661[1-(4-cyanophenyl)-1H-pyrazol-5-yl]boronic acidHCID 673427675-iodo-N,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide

Product 1

HCID 177551515-[1-(4-Cyanophenyl)-1H-pyrazol-5-yl]-N,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamideYield 36.4%

Reagents, catalysts & solvents 4

HCID 71406666Palladium--tri-tert-butylphosphane (1/1)Catalyst2×HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
82 °C

Procedure

Argon was bubbled through 5-iodo-N,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2-dihydropyridine-3-carboxamide (SM2, 200 mg, 0.46 mmol) and [1-(4-cyanophenyl)-1H-pyrazol-5-yl]boronic acid (SM3, 150 mg, 0.70 mmol) in DME (10 ml) and 2M Na2CO3 (5 ml) for 10 min. Palladium-tri-tert-butylphosphine (25 mg, 0.049 mmol) was added and the mixture was stirred under argon at 82° C. for 2 h. More SM3 (150 mg, 0.70 mmol) and palladium-tri-tert-butylphosphine (10 mg, 0.019 mmol) were added and the mixture was stirred for a further 2 h under the same conditions. The reaction mixture was then was cooled to RT, diluted with ethyl acetate (150 ml) and washed with brine (3×100 ml). The organic phase was dried (Na2SO4), filtered and evaporated. The residue was purified by HPLC on a Kromasil C-18 column using a gradient of acetonitrile/water. Freeze-drying of the mixture afforded the title compound (80 mg).

Workup

  1. stirringthe mixture was stirred for a further 2 h under the same conditions
  2. temperatureThe reaction mixture was then was cooled to RT
  3. washwashed with brine (3×100 ml)
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by HPLC on a Kromasil C-18 column
  8. customFreeze-drying of the mixture

Sources & evidence

ORD record
ord-7aa6b3ca26574272aff41853856d94cc
Source dataset
uspto-grants-2011_08
Patent number
US07998984B2

Reaction notes

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