Cesium fluoride → methyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylate

HRID 923690Notes

Reaction equation

HRID 923690 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[C:6](Cl)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[Cl:14].[F:15][C:16]1[C:17](B2OC(C)(C)C(C)(C)O2)=[CH:18][CH:19]=[C:20]2[C:24]=1[NH:23][CH:22]=[CH:21]2.[F-].[Cs+].[F-].[K+]>C(#N)C.O.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>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:17]2[C:16]([F:15])=[C:24]3[C:20]([CH:21]=[CH:22][NH:23]3)=[CH:19][CH:18]=2)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[Cl:14]

Participants

8

Reactant 4

HCID 25953Cesium fluoride2×HCID 522689Potassium FluorideHCID 22677265Methyl 4-amino-3,6-dichloro-5-fluoropicolinateHCID 904180787-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole

Product 1

HCID 78319091methyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylateYield 56.3%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

Methyl 4-amino-3,6-dichloro-5-fluoropicolinate (0.650 g, 2.72 mmol), 7-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (0.817 g, 3.13 mmol), bis(triphenylphosphine)palladium(II) chloride (0.191 g, 0.272 mmol), and cesium fluoride (0.826 g, 5.44 mmol, Note: potassium fluoride replaced cesium fluoride in some examples that refer to this particular example) were combined in acetonitrile (4.53 mL) and water (4.53 mL). The reaction mixture was irradiated in a Biotage Initiator microwave at 110° C. in a sealed vial for 30 min. The cooled reaction mixture was partitioned between ethyl acetate and water. The organic phase was dried and concentrated. The product was purified by flash chromatography (SiO2; eluting with 5-40% ethyl acetate in hexanes) to provide the title compound as an white solid (0.517 g, 52.4% yield).

Workup

  1. customThe reaction mixture was irradiated in a Biotage Initiator microwave at 110° C. in a sealed vial for 30 min
  2. customThe cooled reaction mixture
  3. customwas partitioned between ethyl acetate and water
  4. customThe organic phase was dried
  5. concentrationconcentrated
  6. customThe product was purified by flash chromatography (SiO2; eluting with 5-40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-d15ce5304bbc49f3bc3076ff9268b7c3
Source dataset
uspto-grants-2016_03
Patent number
US09278985B2

Reaction notes

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