Potassium Carbonate → 5-chloro-6-methyl-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 629078Notes

Reaction equation

HRID 629078 reaction equation
[Cl:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[C:23]([O-])([O-])=O.[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[Cl:1][C:2]1[C:3]([CH3:23])=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8]

Participants

5

Reactant 2

HCID 11430Potassium CarbonateHCID 81946485,6-dichloro-N-[4-(trifluoromethoxy)phenyl]pyridine-3-carboxamide

Product 1

HCID 899068685-chloro-6-methyl-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

5,6-dichloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 43.2, 500 mg, 1.424 mmol), trimethylboroxime (179 mg, 1.424 mmol), Pd(PPh3)4, (165 mg, 0.142 mmol), K2CO3 (295 mg, 2.136 mmol) and dioxane (4069 μL) were added to a vial, which was sealed, evacuated/purged with argon and the RM was stirred at 110° C. for 72 h. The RM was filtered through a pad of Celite®, which was washed with EtOAc. The combined filtrates were evaporated to dryness under reduced pressure and the residue was purified by flash chromatography (Silica gel column, 24 g, cyclohexane/EtOAc-EtOH (9:1)+0.1% NH4OH, gradient from 5% to 25% EtOAc-EtOH (9:1)+0.1% NH4OH) and recrystallized from cyclohexane/EtOAc to afford the title compound as a light yellow solid. UPLC-MS (Condition 1) tR=2.76 min, m/z=331.0 [M+H]+, m/z=329.0 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.64 (s, 3H) 7.39 (d, J=9.05 Hz, 2H) 7.87 (d, J=9.05 Hz, 2H) 8.38 (d, J=1.71 Hz, 1H) 8.94 (d, J=1.96 Hz, 1H) 10.60 (s, 1H).

Workup

  1. customwas sealed
  2. customevacuated/purged with argon
  3. filtrationThe RM was filtered through a pad of Celite®, which
  4. washwas washed with EtOAc
  5. customThe combined filtrates were evaporated to dryness under reduced pressure
  6. customthe residue was purified by flash chromatography (Silica gel column, 24 g, cyclohexane/EtOAc-EtOH (9:1)+0.1% NH4OH, gradient from 5% to 25% EtOAc-EtOH (9:1)+0.1% NH4OH)
  7. customrecrystallized from cyclohexane/EtOAc

Sources & evidence

ORD record
ord-23ce124e56ec4a5698e7d3ae2b2f6548
Source dataset
uspto-grants-2016_04
Patent number
US09315489B2

Reaction notes

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