Lithium Chloride → 6'-(Pyridazin-4-yl)-2-fluoro-5-(4-piperidin-1-ylmethylphenyl)-[3,4']bipyridinyl-3'-ylamine

HRID 1506076Notes

Reaction equation

HRID 1506076 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]2[C:10]([F:28])=[N:11][CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][N:22]4[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]4)=[CH:17][CH:16]=3)[CH:14]=2)[CH:3]=1.C([Sn](CCCC)(CCCC)[C:34]1[CH:39]=[CH:38][N:37]=[N:36][CH:35]=1)CCC.[Cl-].[Li+]>O1CCOCC1.C(Cl)Cl.CO.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[N:36]1[CH:35]=[CH:34][C:39]([C:2]2[N:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]3[C:10]([F:28])=[N:11][CH:12]=[C:13]([C:15]4[CH:20]=[CH:19][C:18]([CH2:21][N:22]5[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]5)=[CH:17][CH:16]=4)[CH:14]=3)[CH:3]=2)=[CH:38][N:37]=1

Participants

8

Reactant 3

HCID 433294Lithium ChlorideHCID 64097334-(Tributylstannyl)pyridazineHCID 582666266'-Bromo-2-fluoro-5-(4-piperidin-1-ylmethylphenyl)-[3,4]bipyridinyl-3'-ylamine

Product 1

HCID 582666076'-(Pyridazin-4-yl)-2-fluoro-5-(4-piperidin-1-ylmethylphenyl)-[3,4']bipyridinyl-3'-ylamine

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 6′-bromo-2-fluoro-5-(4-piperidin-1-ylmethylphenyl)-[3,4]bipyridinyl-3′-ylamine (200 mg, 0.45 mmol), 4-(tributylstannyl)pyridazine (334 mg, 0.91 mmol) and lithium chloride (192 mg, 4.5 mmol) in 1,4-dioxane (5 mL) was degassed and flushed with nitrogen. Tetrakis(triphenylphosphine)-palladium(0) (39 mg, 0.034 mmol) was added and the reaction was heated at 110° C. for 24 h. The cooled reaction mixture was diluted with DCM (20 mL) and methanol (2 mL) and washed with water (15 mL). The organic phase was separated, dried over sodium sulfate, filtered and evaporated in vacuo to afford a residue that was purified by flash chromotagraphy (silica, 10 g column, Biotage, 0-10% methanol in DCM containing 0 1% ammonia) to afford a brown residue that was taken to the next step without further purification.

Workup

  1. customwas degassed
  2. customflushed with nitrogen
  3. customThe cooled reaction mixture
  4. washwashed with water (15 mL)
  5. customThe organic phase was separated
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customto afford a residue that
  10. customwas purified by flash chromotagraphy (silica, 10 g column, Biotage, 0-10% methanol in DCM containing 0 1% ammonia)
  11. customto afford a brown residue that
  12. customwas taken to the next step without further purification

Sources & evidence

ORD record
ord-62f2fc4e3a794bb2a92be155339777b5
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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