Cesium fluoride → Methyl 6-amino-2-(6-fluorobenzo[c][1,2,5]oxadiazol-5-yl)-5-methoxypyrimidine-4-carboxylate

HRID 1468973

Reaction equation

[NH2:1][C:2]1[N:7]=[C:6](Cl)[N:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[C:3]=1[O:13][CH3:14].[F:15][C:16]1[C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][C:19]2=[N:20][O:21][N:22]=[C:18]2[CH:17]=1.[F-].[Cs+]>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(#N)C.O>[NH2:1][C:2]1[N:7]=[C:6]([C:24]2[C:16]([F:15])=[CH:17][C:18]3=[N:22][O:21][N:20]=[C:19]3[CH:23]=2)[N:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[C:3]=1[O:13][CH3:14]

Participants

Conditions

Temperature: 115 °C

Procedure

Methyl 6-amino-2-chloro-5-methoxypyrimidine-4-carboxylate (400 mg, 1.838 mmol), 5-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[c][1,2,5]oxadiazole (789 mg, 2.390 mmol), bis(triphenylphosphine)palladium(II) chloride (129 mg, 0.184 mmol), and cesium fluoride (558 mg, 3.68 mmol) were combined in 4 mL 1:1 ACN-water and heated at 115° C. for 30 min in a microwave reactor. The cooled reaction mixture was partitioned between ethyl acetate and water. The organic phase was washed with saturated NaCl, dried, and evaporated. The product was purified by flash chromatography (SiO2, eluting with 5-30% ethyl acetate in dichloromethane) to provide the title compound (240 mg, 39%).

Workup

customThe cooled reaction mixture
customwas partitioned between ethyl acetate and water
washThe organic phase was washed with saturated NaCl
customdried
customevaporated
customThe product was purified by flash chromatography (SiO2, eluting with 5-30% ethyl acetate in dichloromethane)

Sources & evidence

ORD record: ord-095fa5622b374946892d12364e65bc40
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09006250B2

Linked notes

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