Sodium Carbonate → 2,3-difluoro-5-(1-methyl-1H-pyrazol-4-yl)pyridine

HRID 2175132Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([F:9])[C:5]([F:8])=[N:6][CH:7]=1.[CH3:10][N:11]1[CH:15]=[C:14](B2OC(C)(C)C(C)(C)O2)[CH:13]=[N:12]1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.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>[F:8][C:5]1[C:4]([F:9])=[CH:3][C:2]([C:14]2[CH:13]=[N:12][N:11]([CH3:10])[CH:15]=2)=[CH:7][N:6]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 5-bromo-2,3-difluoropyridine (1.9 g, 9.79 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (2.038 g, 9.79 mmol), Na2CO3 (2.076 g, 19.59 mmol) and Pd(PPh3)4 (1.131 g, 0.979 mmol) in DMF (8 ml) was bubbled with N2 for 10 min and was then heated to 80° C. for 10 h. After being cooled to rt, the mixture was filtered and the filtrate was diluted with EA, washed with water and brine, dried over anhydrous MgSO4. Filtered and concentrated. The residue was purified by silica gel chromatography eluted with Hex/EA (from 100% to 20%) to afford the title compound as a white solid (1.5 g, 57.4% yield). 1H-NMR (400 MHz, DMSO-d6) δ ppm 8.29 (d, 3H), 7.99 (d, 1H), 3.87 (s, 3H). LCMS (method B): [M+H]+=196, tR=1.91 min.

Workup

customwas bubbled with N2 for 10 min
temperatureAfter being cooled to rt
filtrationthe mixture was filtered
additionthe filtrate was diluted with EA
washwashed with water and brine
dry with materialdried over anhydrous MgSO4
filtrationFiltered
concentrationconcentrated
customThe residue was purified by silica gel chromatography
washeluted with Hex/EA (from 100% to 20%)

Sources & evidence

ORD record: ord-46595d96c8624a0ba7db52cae7e5df53
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09062045B2

Reaction notes

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