Water → 4-Chloro-2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridine

HRID 2409233Notes

Reaction equation

Cl[C:2]1[CH:11]=[C:10]([Cl:12])[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([F:23])=[C:18](B(O)O)[CH:19]=1.O>CN(C=O)C.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:12][C:10]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=[C:2]([C:16]2[CH:15]=[C:14]([Cl:13])[CH:19]=[CH:18][C:17]=2[F:23])[CH:11]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 9.95 g (50.0 mmol) 2,4-dichloro-[1,8]naphthyridine (described by Koller, Chemische Berichte 60: 407 (1927)), 8.72 g (50.0 mmol) 5-chloro-2-fluorophenylboronic acid und 5.04 g (60.0 mmol) sodium hydrogencarbonate in 100 ml DMF und 50 ml water was heated to 80° C. under nitrogen. 701 mg (1.0 mmol) bis-(triphenylphosphine)-palladium(II)-chloride were added and the mixture was stirred for 16 hrs at 80° C. Water was added to the reaction mixture and the precipitate was filtered off, dried in vacuum and re-crystallized from 2-propanole. This yielded 4-chloro-2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridine as yellowish crystals; HPLC-MS: 2.49 min, [M+H] 293. 1H NMR (400 MHz, CDCl3) δ [ppm]=9.14 (dd, J=4.2, 1.9, 1H), 8.56 (dd, J=8.3, 1.9, 1H), 8.37 (dd, J=6.8, 2.7, 1H), 8.10 (d, J=1.6, 1H), 7.56 (dd, J=8.4, 4.2, 1H), 7.36 (ddd, J=8.7, 4.2, 2.8, 1H), 7.10 (dd, J=10.9, 8.8, 1H).

Workup

filtrationthe precipitate was filtered off
customdried in vacuum
customre-crystallized from 2-propanole
custom2.49 min, [M+H] 293

Sources & evidence

ORD record: ord-b5ec745d97b3422092f92f50349c4ff7
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08815893B2

Reaction notes

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