Cesium carbonate → (3-Fluoro-[2,4]bipyridinyl-3'-yl)-methyl-amine

HRID 878049Notes

Reaction equation

HRID 878049 reaction equation
C[N:2]([C:19]1[CH:20]=[N:21][CH:22]=[CH:23][C:24]=1N1CCCCC1C)[C:3](=O)C1C=C(C(F)(F)F)C=C(C(F)(F)F)C=1.[F:32][C:33]1[C:34](B2OC(C)(C)C(C)(C)O2)=[N:35][CH:36]=[CH:37][CH:38]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].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.[Fe+2].Cl[Cu]>[F:32][C:33]1[C:34]([C:24]2[CH:23]=[CH:22][N:21]=[CH:20][C:19]=2[NH:2][CH3:3])=[N:35][CH:36]=[CH:37][CH:38]=1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 177504653-Fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 86670691N-Methyl-N-(2-methyl-3,4,5,6-tetrahydro-2H-[1,4']bipyridinyl-3'-yl)-3,5-bis-trifluoromethyl-benzamide2×

Product 1

HCID 68294041(3-Fluoro-[2,4]bipyridinyl-3'-yl)-methyl-amineYield 92.2%

Reagents, catalysts & solvents 4

HCID 62652Cuprous chlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of compound (4-bromo-pyridin-3-yl)-methyl-amine (50 mg, 0.267 mmol, example 25, intermediate b) and 3-fluoro pyridine-2-boronic acid pinacol ester (Milestone Pharmtech LLC) (89.4 mg 0.4 mmol) dissolved in dry DMF (3 mL) in a sealed tube was added cesium carbonate (348.4 mg, 1.07 mmol) and the reaction mixture was purged with argon for 10 min. Then Pd(OAc)2 (9.38 mg, 0.013 mmol), dppf (1.48 mg, 0.0026 mmol) and CuCl (26.46 mg, 0.27 mmol) were added to the reaction mixture and again purged with nitrogen for 15 min. The reaction mixture was heated at 100° C. for 16 hours. The reaction mixture was cooled to 25° C., filtered through a bed of celite and washed with EtOAc. The organic layer was washed with water, dried over sodium sulphate and evaporated to yield the desired compound as a light yellow solid (50 mg, 92%) which was used in next step without further purification. MS (ESI): m/z=204.2 [M+H]+.

Workup

  1. customthe reaction mixture was purged with argon for 10 min
  2. customagain purged with nitrogen for 15 min
  3. temperatureThe reaction mixture was cooled to 25° C.
  4. filtrationfiltered through a bed of celite
  5. washwashed with EtOAc
  6. washThe organic layer was washed with water
  7. dry with materialdried over sodium sulphate
  8. customevaporated

Sources & evidence

ORD record
ord-14eb9e5da0274903844a74c9025557eb
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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