Sodium Carbonate → 5-(3'-Chloro-6-fluorobiphenyl-3-yl)-2-trifluoromethyl[1,8]naphthyridine

HRID 1061822Notes

Reaction equation

HRID 1061822 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[C:12](=[N:13][C:14]([C:18]([F:21])([F:20])[F:19])=[CH:15][CH:16]=3)[N:11]=[CH:10][CH:9]=2)=[CH:4][C:3]=1OS(C(F)(F)F)(=O)=O.[Cl:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.ClCCl.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:30][C:31]1[CH:36]=[C:35]([C:3]2[C:2]([F:1])=[CH:7][CH:6]=[C:5]([C:8]3[CH:9]=[CH:10][N:11]=[C:12]4[C:17]=3[CH:16]=[CH:15][C:14]([C:18]([F:19])([F:20])[F:21])=[N:13]4)[CH:4]=2)[CH:34]=[CH:33][CH:32]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 2734323(3-Chlorophenyl)boronic acidHCID 86594178Trifluoromethanesulfonic acid 2-fluoro-5-(7-trifluoromethyl[1,8]naphthyridin-4-yl)phenyl ester

Product 1

HCID 101579765-(3'-Chloro-6-fluorobiphenyl-3-yl)-2-trifluoromethyl[1,8]naphthyridineYield 46.4%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of trifluoromethanesulfonic acid 2-fluoro-5-(7-trifluoromethyl-[1,8]naphthyridin-4-yl)phenyl ester (30.0 mg, 0.068 mmol), 3-chlorobenzeneboronic acid (13.9 mg, 0.089 mmol), dichlorobis-(triphenylphosphine)palladium(II) (5.0 mg, 7.1 μmol) and 2 M sodium carbonate solution (0.5 mL) in DME (3 mL) was irradiated in a microwave reactor at 150° C. for 10 min. After cooling to room temperature, the mixture was diluted with dichloromethane (3 mL) and water (3 mL), and was filtered through a PTFE cartridge. The separated organic phase was concentrated in vacuo, and the residual material was purified by preparative thin layer chromatography on silica gel, eluting with 5% ethyl acetate in dichloromethane, affording 5-(3′-chloro-6-fluorobiphenyl-3-yl)-2-trifluoromethyl[1,8]naphthyridine as a white solid (12.7 mg, 46%). δH (360 MHz, CDCl3) 7.33-7.50 (5H, m), 7.57 (1H, dd, J 1.8 and 7.0), 7.59-7.60 (2H, m), 7.84 (1H, d, J 8.8), 8.54 (1H, d, J 8.8), 9.29 (1H, d, J 4.2). m/z (ES+) 403, 405 [MH]+.

Workup

  1. customwas irradiated in a microwave reactor at 150° C. for 10 min
  2. filtrationwas filtered through a PTFE cartridge
  3. concentrationThe separated organic phase was concentrated in vacuo
  4. customthe residual material was purified by preparative thin layer chromatography on silica gel
  5. washeluting with 5% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-45e8de259dd34b6da65f95f1fe8f7d4f
Source dataset
uspto-grants-2005_11
Patent number
US06960598B2

Reaction notes

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