Toluene → 6'-(Dimethylamino)-N-((2'-fluoro-2,4'-bipyridin-5-yl)methyl)-3,3'-bipyridine-6-carboxamide

HRID 711246Notes

Reaction equation

HRID 711246 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:10][CH2:11][C:12]2[CH:13]=[CH:14][C:15]([C:18]3[CH:23]=[CH:22][N:21]=[C:20]([F:24])[CH:19]=3)=[N:16][CH:17]=2)=[O:9])=[N:6][CH:7]=1.[CH3:25][N:26]([CH3:36])[C:27]1[N:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C1(C)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>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.C(O)C>[CH3:25][N:26]([CH3:36])[C:27]1[N:32]=[CH:31][C:30]([C:2]2[CH:7]=[N:6][C:5]([C:8]([NH:10][CH2:11][C:12]3[CH:13]=[CH:14][C:15]([C:18]4[CH:23]=[CH:22][N:21]=[C:20]([F:24])[CH:19]=4)=[N:16][CH:17]=3)=[O:9])=[CH:4][CH:3]=2)=[CH:29][CH:28]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27632716-(Dimethylamino)pyridine-3-boronic acidHCID 672086435-bromo-N-((2'-fluoro-2,4'-bipyridin-5-yl)methyl)picolinamide

Product 1

HCID 565988876'-(Dimethylamino)-N-((2'-fluoro-2,4'-bipyridin-5-yl)methyl)-3,3'-bipyridine-6-carboxamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

To a tube was added 5-bromo-N-((2′-fluoro-2,4′-bipyridin-5-yl)methyl)picolinamide 38-4 (38 mg, 0.10 mmol), 6-(dimethylamino)pyridin-3-ylboronic acid 38-5 (33 mg, 0.20 mmol), Pd(PPh3)4 (11 mg, 0.01 mmol), toluene (0.4 mL), ethanol (0.1 mL) and 2M Na2CO3 (0.15 mL). The reaction mixture was bubbled with nitrogen for 2 minutes and stirred at 90° C. for 10 hours with the tube sealed. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (100 mL) and washed with saturated NaHCO3 aqueous solution, H2O and brine. The organic phase was dried over Na2SO4 and concentrated to dryness by rotary evaporation. The crude product was purified with reverse phase HPLC to give 6′-(dimethylamino)-N-((2′-fluoro-2,4′-bipyridin-5-yl)methyl)-3,3′-bipyridine-6-carboxamide 38 as a white powder. MS m/z 429.20 (M+1); 1H NMR 400 MHz (DMSO-d6) δ 9.52 (t, 1H, J=6.4 Hz), 8.94 (d, 1H, J=2.4 Hz), 8.73 (d, 1H, J=2.0 Hz), 8.60 (d, 1H, J=2.4 Hz), 8.35 (d, 1H, J=5.2 Hz), 8.22 (m, 1H), 8.15 (d, 1H, J=8.0 Hz), 8.06-7.93 (m, 4H), 7.80 (s, 1H), 6.78 (d, 1H, J=9.2 Hz), 4.60 (d, 2H, J=6.4 Hz), 3.09 (s, 6H).

Workup

  1. customThe reaction mixture was bubbled with nitrogen for 2 minutes
  2. customsealed
  3. temperatureAfter cooling to room temperature
  4. additionthe reaction mixture was diluted with ethyl acetate (100 mL)
  5. washwashed with saturated NaHCO3 aqueous solution, H2O and brine
  6. dry with materialThe organic phase was dried over Na2SO4
  7. concentrationconcentrated to dryness by rotary evaporation
  8. customThe crude product was purified with reverse phase HPLC

Sources & evidence

ORD record
ord-e9b61db8d1ff493ea44af374217c02e2
Source dataset
uspto-grants-2015_11
Patent number
US09181235B2

Reaction notes

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