Dichloromethane → 5-[2-(5-Chloro-2-fluoro-phenyl)-[1,8]naphthyridin-4-yl]-pyridin-2-ylamine

HRID 1404287Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][N:3]=1.[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([F:29])=[C:14]([C:16]2[CH:25]=[C:24](B(O)O)[C:23]3[C:18](=[N:19][CH:20]=[CH:21][CH:22]=3)[N:17]=2)[CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+].ClCCl>O1CCOCC1.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([F:29])=[C:14]([C:16]2[CH:25]=[C:24]([C:5]3[CH:6]=[CH:7][C:2]([NH2:1])=[N:3][CH:4]=3)[C:23]3[C:18](=[N:19][CH:20]=[CH:21][CH:22]=3)[N:17]=2)[CH:15]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A slurry of 352 mg (2.04 mmol) 2-amino-5-bromo-pyridine, 678 mg (2.24 mmol) 2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridine-4-boronic acid and 1.33 g (4.07 mmol) cesium carbonate in 10 ml dioxane and 2 ml water was heated to 80° C. under nitrogen. Then 118 mg (0.10 mmol) tetrakis-(triphenylphosphine)-palladium(0) were added and the reaction mixture was stirred for 1 hour at 100° C. The reaction mixture was cooled to room temperature and water and dichloromethane were added. The resulting precipitate was filtered off, washed with water and dried in vacuo yielding 5-[2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridin-4-yl]-pyridin-2-ylamine as brown crystals; HPLC-MS: 1.43 min,

Workup

temperatureThe reaction mixture was cooled to room temperature
filtrationThe resulting precipitate was filtered off
washwashed with water
customdried in vacuo

Sources & evidence

ORD record: ord-3401dd8bc92d402397fb1e4faefaee9a
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08912216B2

Reaction notes

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