2-Chloropyridine → N-(4-(3-(pyridin-4-yl)pyridin-2-yloxy)phenyl)pyridin-2-amine

HRID 473608Notes

Reaction equation

[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[C:8]([O:13][C:14]3[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=3)=[N:9][CH:10]=[CH:11][CH:12]=2)=[CH:3][CH:2]=1.Cl[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:1]1[CH:2]=[CH:3][C:4]([C:7]2[C:8]([O:13][C:14]3[CH:19]=[CH:18][C:17]([NH:20][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)=[CH:16][CH:15]=3)=[N:9][CH:10]=[CH:11][CH:12]=2)=[CH:5][CH:6]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A glass microwave reaction vessel was charged with 4-(3-(pyridin-4-yl)pyridin-2-yloxy)benzenamine (0.0965 g, 0.37 mmol), 2-chloropyridine (0.034 mL, 0.36 mmol), palladium(II) acetate (0.0098 g, 0.018 mmol), BINAP (0.0213 g, 0.037 mmol), and sodium tert-butoxide (0.0503 g, 0.55 mmol). The reaction mixture was stirred and heated in a Smith Synthesizer® microwave reactor (Personal Chemistry, Inc., Upssala, Sweden) at 120° C. for 45 min. Reaction was concentrated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage™ pre-packed silica gel column (25M), eluting with a gradient of 1% to 5% methanol in DCM, to provide N-(4-(3-(pyridin-4-yl)pyridin-2-yloxy)phenyl)pyridin-2-amine. MS (ESI, pos. ion) m/z: 341.1 (M+1). IC50 (uM) 0.000659.

Workup

customA glass microwave reaction vessel
customReaction
concentrationwas concentrated
customchromatographed through a Biotage™ pre-packed silica gel column (25M)
washeluting with a gradient of 1% to 5% methanol in DCM

Sources & evidence

ORD record: ord-6307647064a64ae98343a28fc26d3bca
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637500B2

Reaction notes

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