Potassium Carbonate → 5-(7-Chloro[1,6]naphthyridin-3-yl)-2-fluoro-4-methylaniline

HRID 715098Notes

Reaction equation

Br[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][N:8]=[C:7]([Cl:12])[CH:6]=2.[F:13][C:14]1[CH:20]=[C:19]([CH3:21])[C:18](B2OC(C)(C)C(C)(C)O2)=[CH:17][C:15]=1[NH2:16].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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>[Cl:12][C:7]1[CH:6]=[C:5]2[C:10]([CH:11]=[C:2]([C:18]3[C:19]([CH3:21])=[CH:20][C:14]([F:13])=[C:15]([CH:17]=3)[NH2:16])[CH:3]=[N:4]2)=[CH:9][N:8]=1

Participants

Conditions

Temperature: 75 °C

Procedure

Sparge a solution of 3-bromo-7-chloro-1,6-naphthyridine (0.5 g, 2.053 mmol) and 2-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.516 g, 2.053 mmol) in dioxane (15 mL) with Ar, add a solution of K2CO3 (0.568 g, 4.11 mmol) in H2O (3 mL), followed by Pd(PPh3)4 (0.237 g, 0.205 mmol), heat at 75° C. for 8 h, then cool to RT. Add H2O, extract with EtOAc (2×), wash the combined organics with brine, dry over Na2SO4, concentrate to dryness and purify via silica gel chromatography (EtOAc/Hex) to afford the title compound (470 mg, 80%) as an off-white solid. MS(ESI) m/z: 288.1 (M+H+).

Workup

temperaturecool to RT
extractionAdd H2O, extract with EtOAc (2×)
washwash the combined organics with brine
dry with materialdry over Na2SO4
concentrationconcentrate to dryness
custompurify via silica gel chromatography (EtOAc/Hex)

Sources & evidence

ORD record: ord-482f0dee0e51449fa5dbd2150d5e45ed
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187474B2

Reaction notes

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