Water → 2'-Methoxy-N-(4-(trifluoromethoxy)phenyl)-[3,3'-bipyridine]-5-carboxamide

HRID 629104Notes

Reaction equation

HRID 629104 reaction equation
Br[C:2]1[CH:3]=[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].[CH3:22][O:23][C:24]1[C:29](B(O)O)=[CH:28][CH:27]=[CH:26][N:25]=1.C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1>[CH3:22][O:23][C:24]1[C:29]([C:2]2[CH:3]=[N:4][CH:5]=[C:6]([C:7]([NH:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=3)=[O:8])[CH:21]=2)=[CH:28][CH:27]=[CH:26][N:25]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 2762709(2-Methoxypyridin-3-yl)boronic acidHCID 46840185-bromo-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 722035682'-Methoxy-N-(4-(trifluoromethoxy)phenyl)-[3,3'-bipyridine]-5-carboxamide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

5-Bromo-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 61.1, 90 mg, 0.25 mmol), 2-methoxypyridin-3-ylboronic acid (45.9 mg, 0.300 mmol), K2CO3 (69.1 mg, 0.500 mmol), PdCl2(dppf)-(CH2Cl2) (20.42 mg, 0.025 mmol), water (0.6 mL) and dioxane (3 mL) were added to a vial, which was sealed, evacuated/purged with argon and the RM was stirred at 60° C. for 1 h. The RM was treated with water and extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (Silica gel column, 15 g, EtOAc) to afford the title compound as a white powder. UPLC-MS (Condition 2) tR=1.1 min, m/z=390.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.93 (s, 3H) 7.19 (dd, J=7.23, 4.89 Hz, 1H) 7.40 (d, J=8.99 Hz, 2H) 7.89 (m, J=9.00 Hz, 2H) 7.97 (dd, J=7.43, 1.96 Hz, 1H) 8.28 (dd, J=5.08, 1.96 Hz, 1H) 8.46 (t, J=2.15 Hz, 1H) 8.97 (d, J=1.95 Hz, 1H) 9.08 (d, J=2.35 Hz, 1H) 10.64 (s, 1H).

Workup

  1. customwas sealed
  2. customevacuated/purged with argon
  3. additionThe RM was treated with water
  4. extractionextracted with EtOAc
  5. washThe combined extracts were washed with water and brine
  6. dry with materialdried over Na2SO4
  7. customthe solvent was evaporated off under reduced pressure
  8. customto give the crude product which
  9. customwas purified by flash chromatography (Silica gel column, 15 g, EtOAc)

Sources & evidence

ORD record
ord-5ce73bce7812443ba41dddd6cffd2e6f
Source dataset
uspto-grants-2016_04
Patent number
US09315489B2

Reaction notes

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