Potassium Carbonate → 2-{6-[4-(pyridin-3-yl)-1H-pyrazol-1-yl]pyridin-2-yl}pyrimidine

HRID 705030Notes

Reaction equation

[NH:1]1[CH:5]=[C:4]([C:6]2[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=2)[CH:3]=[N:2]1.Br[C:13]1[N:18]=[C:17]([C:19]2[N:24]=[CH:23][CH:22]=[CH:21][N:20]=2)[CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[N:8]1[CH:9]=[CH:10][CH:11]=[C:6]([C:4]2[CH:5]=[N:1][N:2]([C:13]3[N:18]=[C:17]([C:19]4[N:20]=[CH:21][CH:22]=[CH:23][N:24]=4)[CH:16]=[CH:15][CH:14]=3)[CH:3]=2)[CH:7]=1

Participants

Conditions

Temperature: 120 °C

Procedure

DMF was added to 0.8 g (5.5 mmol) of 3-(1H-pyrazol-4-yl)pyridine (Angew. Chemie, 2006, 118 (8) 1304), 1.3 g (5.5 mmol) of 2-(6-bromopyridin-2-yl)pyrimidine (WO 2010/006713), 0.29 g (0.82 mmol) of copper-8-hydroxyquinoline complex (cf. Tetrahedron Lett, 2006, 149) and 2.28 g (16.5 mmol) of potassium carbonate, and the mixture was stirred at 120° C. under argon for 16 hours. The entire reaction mixture was then concentrated under reduced pressure. The residue was admixed with aqueous citric acid, aqueous sodium chloride, ethyl acetate and diluted aqueous sodium hydroxide solution until the mixture gave an alkaline reaction (pH=9), the mixture was extracted four times with ethyl acetate and the combined organic phases were dried with sodium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (mobile phase: cyclohexane/acetone). This gave 0.56 g (32% of theory) of 2-{6-[4-(pyridin-3-yl)-1H-pyrazol-1-yl]pyridin-2-yl}pyrimidine.

Workup

customThe entire reaction mixture
concentrationwas then concentrated under reduced pressure
customgave
customan alkaline reaction (pH=9)
extractionthe mixture was extracted four times with ethyl acetate
dry with materialthe combined organic phases were dried with sodium sulfate
concentrationconcentrated under reduced pressure
customThe residue was purified by chromatography on silica gel (mobile phase: cyclohexane/acetone)

Sources & evidence

ORD record: ord-dfc4eb85dce447bd8e6e7a141bc442cd
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09173396B2

Reaction notes

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