2-Bromo-5-methylpyridine → 5-methyl-N-(4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)pyridin-2-amine

HRID 473679Notes

Reaction equation

[O:1]1[CH2:6][CH2:5][CH:4]([C:7]2[C:8]([O:13][C:14]3[CH:20]=[CH:19][C:17]([NH2:18])=[CH:16][CH:15]=3)=[N:9][CH:10]=[CH:11][N:12]=2)[CH2:3][CH2:2]1.Br[C:22]1[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][N:23]=1.CC(C)([O-])C.[Na+]>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+]>[CH3:28][C:25]1[CH:26]=[CH:27][C:22]([NH:18][C:17]2[CH:19]=[CH:20][C:14]([O:13][C:8]3[C:7]([CH:4]4[CH2:3][CH2:2][O:1][CH2:6][CH2:5]4)=[N:12][CH:11]=[CH:10][N:9]=3)=[CH:15][CH:16]=2)=[N:23][CH:24]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A glass microwave reaction vessel was charged with 4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)aniline (0.251 g, 0.925 mmol), 2-bromo-5-methylpyridine (0.133 g, 0.7708 mmol), BrettPHOS precatalyst (0.012 g, 0.015 mmol), and sodium tert-butoxide (0.185 g, 1.927 mmol). The flask was placed under vacuum then flushed with argon. Dioxane (2.57 mL) was added and the reaction was heated to 90° C. to stir overnight. The crude product was adsorbed onto a plug of silica gel and chromatographed to provide 5-methyl-N-(4-(3-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yloxy)phenyl)pyridin-2-amine. MS (ESI, pos. ion) m/z: 363.1. IC50 (uM) 0.000178.

Workup

customA glass microwave reaction vessel
customthen flushed with argon
additionDioxane (2.57 mL) was added
customchromatographed

Sources & evidence

ORD record: ord-8ad80f576f3e47c3a2f23cf4feb16d24
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637500B2

Reaction notes

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