Tributylvinyltin → HCID 58266301, compound

HRID 1888503Notes

Reaction equation

HRID 1888503 reaction equation
Br[C:2]1[C:3]([C:10]2[C:11]([F:29])=[N:12][CH:13]=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([CH2:22][N:23]4[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]4)=[CH:18][CH:17]=3)[CH:15]=2)=[C:4]([NH2:9])[CH:5]=[N:6][C:7]=1[Cl:8].[CH:30]([Sn](CCCC)(CCCC)CCCC)=[CH2:31].[Cl-].[Li+]>O1CCOCC1.O.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>[Cl:8][C:7]1[N:6]=[CH:5][C:4]([NH2:9])=[C:3]([C:10]2[C:11]([F:29])=[N:12][CH:13]=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([CH2:22][N:23]4[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]4)=[CH:18][CH:17]=3)[CH:15]=2)[C:2]=1[CH:30]=[CH2:31]

Participants

7

Reactant 3

HCID 81998TributylvinyltinHCID 433294Lithium ChlorideHCID 58266759HCID 58266759, compound

Product 1

HCID 58266301HCID 58266301, compoundYield 95.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 5′-bromo-6′-chloro-2-fluoro-5-(4-piperidin-1-ylmethyl-phenyl)-[3,4]bipyridinyl-3′-ylamine (93 mg, 0.19 mmol), vinyltributyl tin (63 μL, 0.21 mmol), tetrakis(triphenylphosphine)palladium(0) (11 mg, 5 mol %) and lithium chloride (25 mg, 0.59 mmol) in 1,4-dioxane (1.0 mL) was heated under reflux for 3.5 h. The reaction mixture was allowed to cool to ambient temperature, diluted with water (10 mL) and extracted with DCM (3×20 mL). The combined organic layer was concentrated in vacuo and the resultant residue purified by flash chromatography (silica, 4 g column, ISCO, 0-10% MeOH in DCM) to afford the title compound as a beige powder (77 mg, 82%). 1H NMR (CDCl3, 400 MHz): 8.50 (dd, J=2.5, 1.0 Hz, 1H), 7.94 (s, 1H), 7.88 (dd, J=8.5, 2.5 Hz, 1H), 7.54-7.47 (m, 4H), 6.53 (dd, J=18.0, 11.5 Hz, 1H), 5.37 (dd, J=11.5, 1.0 Hz, 1H), 5.11 (dd, J=18.0, 1.0 Hz, 1H), 3.60 (s, 2H), 3.55-3.50 (m, 2H), 2.48-2.35 (m, 4H), 1.68-1.58 (m, 4H), 1.50-1.44 (m, 2H). LCMS (Method B): RT=2.32 min, M+H+=423/425.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 3.5 h
  3. extractionextracted with DCM (3×20 mL)
  4. concentrationThe combined organic layer was concentrated in vacuo
  5. customthe resultant residue purified by flash chromatography (silica, 4 g column, ISCO, 0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-f71cd5539c614f319b0b90bc788cc1e9
Source dataset
uspto-grants-2013_08
Patent number
US08501765B2

Reaction notes

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