Potassium Carbonate → 5-((2-(Pyrimidin-5-yl)pyridin-4-yl)oxy)pyridin-2-amine

HRID 1049347Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([NH2:15])=[N:13][CH:14]=2)[CH:5]=[CH:4][N:3]=1.B(O)(O)[C:17]1[CH:22]=[N:21][CH:20]=[N:19][CH:18]=1.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>[N:19]1[CH:18]=[C:17]([C:2]2[CH:7]=[C:6]([O:8][C:9]3[CH:10]=[CH:11][C:12]([NH2:15])=[N:13][CH:14]=3)[CH:5]=[CH:4][N:3]=2)[CH:22]=[N:21][CH:20]=1

Participants

Conditions

Temperature: 95 °C

Procedure

A solution of Example A9 (0.25 g, 1.128 mmol) and pyrimidinyl-5-boronic acid (0.196 g, 1.579 mmol) in dioxane (8 mL) was treated with a solution of K2CO3 (0.156 g, 1.128 mmol) in water (2 mL), Pd(PPh3)4 (0.130 g, 0.113 mmol) and heated at 95° C. for 20 h. The mixture was cooled to RT, treated with water and extracted with EtOAc (2×). The combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford 5-((2-(pyrimidin-5-yl)pyridin-4-yl)oxy)pyridin-2-amine (65 mg, 22%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 9.39 (s, 2H), 9.24 (s, 1H), 8.55 (d, J=5.7 Hz, 1H), 7.84 (d, J=3.0 Hz, 1H), 7.75 (d, J=2.4 Hz, 1H), 7.32 (dd, J=8.9, 3.0 Hz, 1H), 6.83 (dd, J=5.7, 2.4 Hz, 1H), 6.53 (d, J=8.9 Hz, 1H), 6.04 (s, 2H); MS (ESI) m/z: 266.1 (M+H+).

Workup

temperatureThe mixture was cooled to RT
extractionextracted with EtOAc (2×)
washThe combined organics were washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated to dryness
custompurified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record: ord-44c7ccc7f7604585b8c9910339d3942e
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382228B2

Reaction notes

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