Potassium Fluoride → Methyl 4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate

HRID 515993Notes

Reaction equation

Cl[C:2]1[N:11]=[CH:10][CH:9]=[C:8]([C:12]#[N:13])[C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH3:14][N:15]1[CH:19]=[C:18](B2OC(C)(C)C(C)(C)O2)[CH:17]=[N:16]1.[F-].[K+]>COCCOC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:12]([C:8]1[C:3]([C:4]([O:6][CH3:7])=[O:5])=[C:2]([C:18]2[CH:17]=[N:16][N:15]([CH3:14])[CH:19]=2)[N:11]=[CH:10][CH:9]=1)#[N:13]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of methyl 2-chloro-4-cyanonicotinate (730 mg, 3.71 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (927 mg, 4.46 mmol), trans-dichlorobis(triphenylphosphine)palladium (261 mg, 0.371 mmol) and potassium fluoride (2697 mg, 14.85 mmol) in DME (15 mL) was stirred at 120° C. for 1 h under microwave irradiation. The mixture was filtered through Celite, and the filtrate was diluted with H2O and EtOAc. The organic phase was washed with H2O and brine, dried over MgSO4, and evaporated. The residue was purified by chromatography on SiO2 to give the title compound as a pale yellow solid (470 mg, 52.3%). 1H NMR (500 MHz, CDCl3) δ ppm 3.97 (s, 3 H), 4.03 (s, 3 H), 7.41 (d, J=4.88 Hz, 1 H), 7.82 (s, 1 H), 7.91 (s, 1 H), 8.79 (d, J=4.88 Hz, 1 H). [M+H] calc'd for C12H10N4O2, 243; found, 243.

Workup

filtrationThe mixture was filtered through Celite
additionthe filtrate was diluted with H2O and EtOAc
washThe organic phase was washed with H2O and brine
dry with materialdried over MgSO4
customevaporated
customThe residue was purified by chromatography on SiO2

Sources & evidence

ORD record: ord-67a6b429c4da46069907e560c03c62ea
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09108970B2

Reaction notes

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