2,6-Dichloropyrazine → HCID 86673735, compound

HRID 1404286Notes

Reaction equation

HRID 1404286 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:21])=[C:6]([C:8]2[CH:17]=[C:16](B(O)O)[C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:7]=1.[Cl:22][C:23]1[CH:28]=[N:27][CH:26]=[C:25](Cl)[N:24]=1.C(=O)(O)[O-].[Na+]>CN(C=O)C.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:21])=[C:6]([C:8]2[CH:17]=[C:16]([C:25]3[CH:26]=[N:27][CH:28]=[C:23]([Cl:22])[N:24]=3)[C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH:7]=1

Participants

7

Reactant 3

HCID 785042,6-DichloropyrazineHCID 516892Sodium BicarbonateHCID 53344730HCID 53344730, compound

Product 1

HCID 86673735HCID 86673735, compound

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 302 mg (1.00 mmol) 2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridine-4-boronic acid, 194 mg (1.30 mmol) 2,6-dichloropyrazine and 101 mg (1.2 mmol) sodium bicarbonate in 4 ml DMF and 1 ml water was heated to 80° C. under nitrogen. Then 14.0 mg (0.02 mmol) bis-(triphenylphosphine)-palladium(II)-chloride were added and the reaction mixture was stirred for 16 hours at 80° C. Water was added to the reaction mixture and the resulting precipitate was filtered off. The residue was chromatographed on a silica gel column with dichloromethane/methanol as eluent yielding 2-(5-chloro-2-fluoro-phenyl)-4-(6-chloro-pyrazin-2-yl)-[1,8]naphthyridine as colourless crystals; HPLC-MS: 2.35 min, [M+H] 371.

Workup

  1. filtrationthe resulting precipitate was filtered off
  2. customThe residue was chromatographed on a silica gel column with dichloromethane/methanol as eluent

Sources & evidence

ORD record
ord-cff973878ae044dd8287347e878ff9af
Source dataset
uspto-grants-2014_12
Patent number
US08912216B2

Reaction notes

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