Sodium Bicarbonate → 2-(5-chloro-2-fluoro-phenyl)-4-[5-(1-methyl-1H-pyrazol-4-yl)-pyridin-3-yl]-[1,8]naphthyridine

HRID 1914941Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[N:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]2[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=2[F:19])[CH:3]=1.[CH3:20][N:21]1[CH:25]=[C:24]([C:26]2[CH:27]=[N:28][CH:29]=[C:30](B3OC(C)(C)C(C)(C)O3)[CH:31]=2)[CH:23]=[N:22]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:18][C:16]1[CH:15]=[CH:14][C:13]([F:19])=[C:12]([C:4]2[CH:3]=[C:2]([C:30]3[CH:29]=[N:28][CH:27]=[C:26]([C:24]4[CH:23]=[N:22][N:21]([CH3:20])[CH:25]=4)[CH:31]=3)[C:11]3[C:6](=[N:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH:17]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A slurry of 147 mg (0.5 mmol) 4-chloro-2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridine, 171 mg (0.6 mmol) 3-(1-methyl-1H-pyrazol-4-yl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine and 50.4 mg (0.6 mmol) sodium bicarbonate in 1 ml DMF and 0.5 ml water was heated to 80° C. under nitrogen. Then 7.0 mg (0.01 mmol) bis-(triphenylphosphine)-palladium(II)-chloride were added. The reaction mixture was stirred for 16 hours at 80° C. Water was then 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-[5-(1-methyl-1H-pyrazol-4-yl)-pyridin-3-yl]-[1,8]naphthyridine als yellow crystals; HPLC-MS: 2.09 min, [M+H] 416.

Workup

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

Sources & evidence

ORD record: ord-97feab2c9db74630860ca316aa7a4a62
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08614226B2

Reaction notes

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