Sodium Carbonate → 3,2'-Difluoro-5'-(7-trifluoromethyl-[1,8]naphthyridin-4-yl)biphenyl-2-carbonitrile

HRID 1061759Notes

Reaction equation

HRID 1061759 reaction equation
Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([C:12]([F:15])([F:14])[F:13])=[N:7]2.C[C:17]1(C)[CH2:22][O:21]B([C:23]2[CH:24]=[CH:25][C:26]([F:38])=[C:27]([C:29]3[C:30]([C:36]#[N:37])=[C:31]([F:35])[CH:32]=[CH:33][CH:34]=3)[CH:28]=2)OC1.C(=O)([O-])[O-:41].[Na+].[Na+]>COCCOC.O.ClCCl.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>[C:22]([O:41][CH2:6][CH3:12])(=[O:21])[CH3:17].[CH3:10][CH2:11][CH2:2][CH:3]([CH3:8])[CH3:4].[F:35][C:31]1[CH:32]=[CH:33][CH:34]=[C:29]([C:27]2[CH:28]=[C:23]([C:2]3[C:3]4[C:8](=[N:7][C:6]([C:12]([F:15])([F:14])[F:13])=[CH:5][CH:4]=4)[N:9]=[CH:10][CH:11]=3)[CH:24]=[CH:25][C:26]=2[F:38])[C:30]=1[C:36]#[N:37]

Participants

9

Reactant 3

HCID 10340Sodium CarbonateHCID 115153815'-(5,5-Dimethyl-[1,3,2]dioxaborinan-2-yl)-3,2'-difluorobiphenyl-2-carbonitrileHCID 222852765-chloro-2-(trifluoromethyl)-1,8-Naphthyridine

Product 2

HCID 101122723,2'-Difluoro-5'-(7-trifluoromethyl-[1,8]naphthyridin-4-yl)biphenyl-2-carbonitrileYield 57.5%HCID 21882781Isohexane ethyl acetate

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

5-Chloro-2-trifluoromethyl[1,8]naphthyridine (50 mg, 0.22 mmol), 5′-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-3,2′-difluorobiphenyl-2-carbonitrile (91 mg, 0.28 mmol), tetrakis(triphenylphosphine)palladium(0) (5.0 mg, 2 mol %) and 2 M sodium carbonate solution (0.5 mL, 1.0 mmol) in DME (3 mL) was irradiated in a microwave reactor at 150° C. for 10 min. The mixture was cooled to room temperature and was diluted with water (3 mL) and dichloromethane (3 mL), and was then filtered through a PTFE cartridge. The separated organic phase was concentrated in vacuo, and the crude product was recrystallised from ethyl acetate, then again from ethyl acetate/isohexane, yielding 3,2′-difluoro-5′-(7-trifluoromethyl-[1,8]naphthyridin-4-yl)biphenyl-2-carbonitrile as an off-white solid (26 mg, 30%). δH (360 MHz, CDCl3) 7.29-7.33 (1H, m), 7.41 (1H, d, J 7.4), 7.48 (1H, t, J 8.9), 7.58-7.61 (3H, m), 7.67-7.73 (1H, m), 7.89 (1H, d, J 8.8), 8.68 (1H, d, J 8.8), 9.29 (1H, dd, J 2.8 and 1.4). m/z (ES+) 412 [MH]+.

Workup

  1. filtrationwas then filtered through a PTFE cartridge
  2. concentrationThe separated organic phase was concentrated in vacuo
  3. customthe crude product was recrystallised from ethyl acetate

Sources & evidence

ORD record
ord-c9cb120820014c1da211057a1ff1fdcb
Source dataset
uspto-grants-2005_11
Patent number
US06960598B2

Reaction notes

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